1.
Fibrinogen alpha chain
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Fibrinogen alpha chain is a protein that in humans is encoded by the FGA gene. The protein encoded by this gene is the component of fibrinogen. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin, in addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia, afibrinogenemia. Alternative splicing results in two isoforms that vary in the carboxy-terminus, fibrinogen alpha chain has been shown to interact with Tissue plasminogen activator
2.
Fibrin
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Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen which causes it to polymerize, the polymerized fibrin together with platelets forms a hemostatic plug or clot over a wound site. When the lining of a vessel is broken, platelets are attracted forming a platelet plug. These platelets have thrombin receptors on their surfaces that bind serum thrombin molecules which in turn convert soluble fibrinogen in the serum into fibrin at the wound site, Fibrin forms long strands of tough insoluble protein that are bound to the platelets. Factor XIII completes the cross-linking of fibrin so that it hardens, the cross-linked fibrin forms a mesh atop the platelet plug that completes the clot. Ineffective generation or premature lysis of fibrin increases the likelihood of a hemorrhage, dysfunction or disease of the liver can lead to a decrease in the production of fibrins inactive precursor, fibrinogen, or to the production of abnormal fibrinogen molecules with reduced activity. Hereditary abnormalities of fibrinogen are both quantitative and qualitative in nature and include afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia, and hypodysfibrinogenaemia, reduced, absent, or dysfunctional fibrin is likely to render patients as hemophiliacs. Fibrin from different animal sources is generally glycosylated with complex type biantennary asparagine linked glycans, variety is found in the degree of core fucosylation and in the type of sialic acid and galactose linkage. The image at the left is a structure of the double-d fragment from human fibrin with two bound ligands. The experimental method used to obtain the image was X-ray diffraction, the structure is mainly made up of single alpha helices shown in red and beta sheets shown in yellow. The two blue structures are the bound ligands, the chemical structures of the ligands are Ca2+ ion, alpha-D-mannose, and D-glucosamine. D-dimer Fibrin glue Fibrin scaffold Fibrinolysis TGW1916. net, Defibrinated blood harvested from sheep Fibrin, Molecule of the Month, by David Goodsell, RCSB Protein Data Bank
3.
Entrez
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The name Entrez was chosen to reflect the spirit of welcoming the public to search the content available from the NLM. Entrez Global Query is a search and retrieval system that provides access to all databases simultaneously with a single query string. Entrez can efficiently retrieve related sequences, structures, and references, the Entrez system can provide views of gene and protein sequences and chromosome maps. Some textbooks are available online through the Entrez system. The Entrez front page provides, by default, access to the global query, all databases indexed by Entrez can be searched via a single query string, supporting boolean operators and search term tags to limit parts of the search statement to particular fields. This returns a unified results page, that shows the number of hits for the search in each of the databases, Entrez also provides a similar interface for searching each particular database and for refining search results. The Limits feature allows the user to narrow a search a web forms interface, the History feature gives a numbered list of recently performed queries. Results of previous queries can be referred to by number and combined via boolean operators, search results can be saved temporarily in a Clipboard. Users with a MyNCBI account can save queries indefinitely and also choose to have updates with new search results e-mailed for saved queries of most databases and it is widely used in the field of biotechnology as a reference tool for students and professionals alike. Entrez searches the following databases, PubMed, biomedical literature citations and abstracts, including Medline - articles from journals, in addition to using the search engine forms to query the data in Entrez, NCBI provides the Entrez Programming Utilities for more direct access to query results. The eUtils are accessed by posting specially formed URLs to the NCBI server, there was also an eUtils SOAP interface which was terminated on July 2015. In 1991, entrez was introduced in CD form, in 1993, a client-server version of the software provided connectivity with the internet. In 1994, NCBI established a website, and Entrez was a part of initial release. In 2001, Entrez bookshelf was released and in 2003, the Entrez Gene database was developed, Entrez search engine form Entrez Help
4.
National Center for Biotechnology Information
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The National Center for Biotechnology Information is part of the United States National Library of Medicine, a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper, the NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. Major databases include GenBank for DNA sequences and PubMed, a database for the biomedical literature. Other databases include the NCBI Epigenomics database, all these databases are available online through the Entrez search engine. NCBI is directed by David Lipman, one of the authors of the BLAST sequence alignment program. He also leads a research program, including groups led by Stephen Altschul, David Landsman, Eugene Koonin, John Wilbur, Teresa Przytycka. NCBI is listed in the Registry of Research Data Repositories re3data. org, NCBI has had responsibility for making available the GenBank DNA sequence database since 1992. GenBank coordinates with individual laboratories and other databases such as those of the European Molecular Biology Laboratory. Since 1992, NCBI has grown to other databases in addition to GenBank. The NCBI assigns a unique identifier to each species of organism, the NCBI has software tools that are available by WWW browsing or by FTP. For example, BLAST is a sequence similarity searching program, BLAST can do sequence comparisons against the GenBank DNA database in less than 15 seconds. RAG2/IL2RG The NCBI Bookshelf is a collection of freely accessible, downloadable, some of the books are online versions of previously published books, while others, such as Coffee Break, are written and edited by NCBI staff. BLAST is a used for calculating sequence similarity between biological sequences such as nucleotide sequences of DNA and amino acid sequences of proteins. BLAST is a tool for finding sequences similar to the query sequence within the same organism or in different organisms. It searches the query sequence on NCBI databases and servers and post the results back to the browser in chosen format. Input sequences to the BLAST are mostly in FASTA or Genbank format while output could be delivered in variety of such as HTML, XML formatting. HTML is the output format for NCBIs web-page. Entrez is both indexing and retrieval system having data from sources for biomedical research
5.
UniProt
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UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains an amount of information about the biological function of proteins derived from the research literature. The UniProt consortium comprises the European Bioinformatics Institute, the Swiss Institute of Bioinformatics, EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy servers that are a resource for proteomics tools. In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium, each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced the Swiss-Prot and TrEMBL databases and these databases coexisted with differing protein sequence coverage and annotation priorities. Swiss-Prot aimed to provide reliable protein sequences associated with a level of annotation. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prots ability to keep up, meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass, a database of protein sequences and curated families. The consortium members pooled their resources and expertise, and launched UniProt in December 2003. UniProt provides four core databases, UniProtKB, UniParc, UniRef, UniProt Knowledgebase is a protein database partially curated by experts, consisting of two sections, UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. As of 19 March 2014, release 2014_03 of UniProtKB/Swiss-Prot contains 542,782 sequence entries, UniProtKB/Swiss-Prot is a manually annotated, non-redundant protein sequence database. It combines information extracted from literature and biocurator-evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings, the manual annotation of an entry involves detailed analysis of the protein sequence and of the scientific literature. Sequences from the gene and the same species are merged into the same database entry. Differences between sequences are identified, and their cause documented, a range of sequence analysis tools is used in the annotation of UniProtKB/Swiss-Prot entries. Computer-predictions are manually evaluated, and relevant results selected for inclusion in the entry and these predictions include post-translational modifications, transmembrane domains and topology, signal peptides, domain identification, and protein family classification. Relevant publications are identified by searching databases such as PubMed, the full text of each paper is read, and information is extracted and added to the entry
6.
Locus (genetics)
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A locus in genetics is the position on a chromosome. Each chromosome carries many genes, humans estimated haploid protein coding genes are 19, 000-20,000, a variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a biological trait. The chromosomal locus of a gene might be written 3p22.1, here 3 means chromosome 3, p means p-arm. And 22 refers to region 2, band 2 and this is read as two two, not as twenty-two. So the entire locus is read as three P two two point one, the cytogenetic bands are counting from the centromere out toward the telomeres. A range of loci is specified in a similar way. For example, the locus of gene OCA1 may be written 11q1. 4-q2.1, meaning it is on the arm of chromosome 11. The ends of a chromosome are labeled pter and qter, a centisome is defined as 1% of a chromosome length. Chromosomal translocation Cytogenetic notation Karyotype Null allele Michael, R. Cummings, belmont, California, Brooks/Cole Overview at ornl. gov Chromosome Banding and Nomenclature from NCBI
7.
Chromosome 4 (human)
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Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, chromosome 4 spans more than 186 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells. Identifying genes on each chromosome is an area of genetic research. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies, in January 2017, two estimates differed by 12%, with one estimate giving 2,441 genes, and the other estimate giving 2,164 genes. The chromosome is ~191 megabases in length, in a 2012 paper, seven hundred and fifty seven protein encoding genes were identified on this chromosome. Two-hundred and eleven of these coding sequences did not have any evidence at the protein level. Two-hundred and seventy one appear to be membrane proteins, fifty-four have been classified as cancer associated proteins. k. a
8.
Fibrinogen beta chain
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Fibrinogen beta chain, also known as FGB, is a gene found in humans and most other vertebrates with a similar system of blood coagulation. The protein encoded by this gene is the component of fibrinogen. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots, in addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this lead to several disorders, including afibrinogenemia, dysfibrinogenemia, hypodysfibrinogenemia. Fibrinogen beta chain has been shown to interact with Lipoprotein
9.
Fibrinogen gamma chain
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Fibrinogen gamma chain, also known as FGG, is a human gene found on Chromosome 4. The protein encoded by this gene is the component of fibrinogen. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots, in addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia and thrombophilia. Alternative splicing of the mRNA chain results in two variants, the common γA chain and the alternatively spliced γ chain. Approximately 10% of the total plasma fibrinogen consists of γA/γ fibrinogen, increased and decreased levels of γA/γ fibrinogen have been associated with CAD and DVT respectively
10.
Pfam
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Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 31.0, was released in March 2017, the general purpose of the Pfam database is to provide a complete and accurate classification of protein families and domains. Originally, the rationale behind creating the database was to have a method of curating information on known protein families to improve the efficiency of annotating genomes. The Pfam classification of families has been widely adopted by biologists because of its wide coverage of proteins. Early genome projects, such as human and fly used Pfam extensively for functional annotation of genomic data, the Pfam website allows users to submit protein or DNA sequences to search for matches to families in the database. If DNA is submitted, a translation is performed, then each frame is searched. Family is the class, which simply indicates that members are related. Domains are defined as a structural unit or reusable sequence unit that can be found in multiple protein contexts. Repeats are not usually stable in isolation, but rather are required to form tandem repeats in order to form a domain or extended structure. Motifs are usually shorter sequence units found outside of globular domains, the descriptions of Pfam families are managed by the general public using Wikipedia. As of release 29.0,76. 1% of protein sequences in UniprotKB matched to at least one Pfam domain, new families come from a range of sources, primarily the PDB and analysis of complete proteomes to find genes with no Pfam hit. For each family, a subset of sequences are aligned into a high-quality seed alignment. Sequences for the alignment are taken primarily from pfamseq with some supplementation from UniprotKB. This seed alignment is used to build a profile hidden Markov model using HMMER. This HMM is then searched against sequence databases, and all hits that reach a curated gathering threshold are classified as members of the protein family, the resulting collection of members is then aligned to the profile HMM to generate a full alignment. For each family, a curated gathering threshold is assigned that maximises the number of true matches to the family while excluding any false positive matches. False positives are estimated by observing overlaps between Pfam family hits that are not from the same clan and this threshold is used to assess whether a match to a family HMM should be included in the protein family. Upon each update of Pfam, gathering thresholds are reassessed to prevent overlaps between new and existing families, domains of Unknown Function represent a growing fraction of the Pfam database
11.
InterPro
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The contents of InterPro consist of diagnostic signatures and the proteins that they significantly match. The signatures consist of models which describe protein families, domains or sites, models are built from the amino acid sequences of known families or domains and they are subsequently used to search unknown sequences in order to classify them. Each of the databases of InterPro contribute towards a different niche, from very high-level. InterPros intention is to provide a one-stop-shop for protein classification, where all the signatures produced by the different member databases are placed into entries within the InterPro database. Signatures which represent equivalent domains, sites or families are put into the same entry, additional information such as a description, consistent names and Gene Ontology terms are associated with each entry, where possible. InterPro contains three main entities, proteins, signatures and entries, the proteins in UniProtKB are also the central protein entities in InterPro. Information regarding which signatures significantly match these proteins are calculated as the sequences are released by UniProtKB, only signatures deemed to be of sufficient quality are integrated into InterPro. InterPro also includes data for splice variants and the contained in the UniParc. The signatures from InterPro come from 11 member databases, which are listed below, cATH-Gene3D describes protein families and domain architectures in complete genomes. Protein families are formed using a Markov clustering algorithm, followed by multi-linkage clustering according to sequence identity, mapping of predicted structure and sequence domains is undertaken using hidden Markov models libraries representing CATH and Pfam domains. Functional annotation is provided to proteins from multiple resources, functional prediction and analysis of domain architectures is available from the Gene3D website. HAMAP stands for High-quality Automated and Manual Annotation of microbial Proteomes, HAMAP profiles are manually created by expert curators they identify proteins that are part of well-conserved bacterial, archaeal and plastid-encoded proteins families or subfamilies. PANTHER is a collection of protein families that have been subdivided into functionally related subfamilies. Hidden Markov models are built for each family and subfamily for classifying additional protein sequences, Pfam is a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains and families. The primary PIRSF classification unit is the family, whose members are both homologous and homeomorphic. PRINTS is a compendium of protein fingerprints, a fingerprint is a group of conserved motifs used to characterise a protein family, its diagnostic power is refined by iterative scanning of UniProt. Usually the motifs do not overlap, but are separated along a sequence, ProDom domain database consists of an automatic compilation of homologous domains. Current versions of ProDom are built using a procedure based on recursive PSI-BLAST searches
12.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
13.
PROSITE
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It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformatics, PROSITE was created in 1988 by Amos Bairoch, who directed the group for more than 20 years. Since July 2009, the director of the PROSITE, Swiss-Prot, pROSITEs uses include identifying possible functions of newly discovered proteins and analysis of known proteins for previously undetermined activity. Properties from well-studied genes can be propagated to biologically related organisms, PROSITE offers tools for protein sequence analysis and motif detection. It is part of the ExPASy proteomics analysis servers, the database ProRule builds on the domain descriptions of PROSITE. It provides additional information about functionally or structurally critical amino acids and these can automatically generate annotation based on PROSITE motifs. As of 29 June 2016, release 20.128 has 1,762 documentation entries,1,309 patterns,1,161 profiles, uniprot — the universal protein database, a central resource on protein information - PROSITE adds data to it. InterPro — a centralized database, grouping data from databases of protein families, domains, protein subcellular localization prediction — another example of use of PROSITE. Official website ProRule — database of rules based on PROSITE predictors
14.
Glycoprotein
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Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification and this process is known as glycosylation. Secreted extracellular proteins are often glycosylated, in proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions and it is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system without reversible cytosolic-nuclear glycosylation. In contrast, classical secretory glycosylation can be structurally essential, for example, inhibition of asparagine-linked, i. e. N-linked, glycosylation can prevent glycoprotein folding and full inhibition can be toxic to an individual cell. In contrast, perturbation of terminal processing, which occurs in the Golgi apparatus, is dispensable for isolated cells but can lead to human disease, a famous example of this latter effect is the ABO blood system. There are several types of glycosylation, although the first two are the most common, in N-glycosylation, sugars are attached to nitrogen, typically on the amide side-chain of asparagine. In O-glycosylation, sugars are attached to oxygen, typically on serine or threonine, in P-glycosylation, sugars are attached to phosphorus on a phosphoserine. In C-glycosylation, sugars are attached directly to carbon, such as in the addition of mannose to tryptophan, in glypiation, a GPI glycolipid is attached to the C-terminus of a polypeptide, serving as a membrane anchor. Monosaccharides commonly found in eukaryotic glycoproteins include, The sugar group can assist in protein folding or improve proteins stability, one example of glycoproteins found in the body is mucins, which are secreted in the mucus of the respiratory and digestive tracts. The sugars when attached to give them considerable water-holding capacity. Glycoproteins are important for blood cell recognition, especially in mammals. Examples of glycoproteins in the system are, molecules such as antibodies. Molecules of the major histocompatibility complex, which are expressed on the surface of cells, sialyl Lewis X antigen on the surface of leukocytes. H antigen of the ABO blood compatibility antigens, other examples of glycoproteins include, glycoprotein IIb/IIIa, an integrin found on platelets that is required for normal platelet aggregation and adherence to the endothelium. Components of the zona pellucida, which surrounds the oocyte, and is important for sperm-egg interaction, structural glycoproteins, which occur in connective tissue. These help bind together the fibers, cells, and ground substance of connective tissue and they may also help components of the tissue bind to inorganic substances, such as calcium in bone. Glycoprotein-41 and glycoprotein-120 are HIV viral coat proteins, soluble glycoproteins often show a high viscosity, for example, in egg white and blood plasma
15.
Vertebrate
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Vertebrates /ˈvɜːrtᵻbrᵻts/ comprise all species of animals within the subphylum Vertebrata /-ɑː/. Vertebrates represent the majority of the phylum Chordata, with currently about 66,000 species described. Vertebrates include the fish and the jawed vertebrates, which include the cartilaginous fish. A bony fish known as the lobe-finned fishes is included with tetrapods, which are further divided into amphibians, reptiles, mammals. Extant vertebrates range in size from the frog species Paedophryne amauensis, at as little as 7.7 mm, to the blue whale, vertebrates make up less than five percent of all described animal species, the rest are invertebrates, which lack vertebral columns. The vertebrates traditionally include the hagfish, which do not have proper vertebrae due to their loss in evolution, though their closest living relatives, hagfish do, however, possess a cranium. For this reason, the vertebrate subphylum is sometimes referred to as Craniata when discussing morphology, molecular analysis since 1992 has suggested that hagfish are most closely related to lampreys, and so also are vertebrates in a monophyletic sense. Others consider them a group of vertebrates in the common taxon of craniata. The word origin of vertebrate derives from the Latin word vertebratus, the Proto-Indo-European language origins are still unclear. Vertebrate is derived from the vertebra, which refers to any of the bones or segments of the spinal column. All vertebrates are built along the basic body plan, a stiff rod running through the length of the animal, with a hollow tube of nervous tissue above it. In all vertebrates, the mouth is found at, or right below, the remaining part of the body continuing after the anus forms a tail with vertebrae and spinal cord, but no gut. However, a few vertebrates have secondarily lost this anatomy, retaining the notochord into adulthood, such as the sturgeon, jawed vertebrates are typified by paired appendages, but this trait is not required in order for an animal to be a vertebrate. All basal vertebrates breathe with gills, the gills are carried right behind the head, bordering the posterior margins of a series of openings from the pharynx to the exterior. Each gill is supported by a cartilagenous or bony gill arch, the bony fish have three pairs of arches, cartilaginous fish have five to seven pairs, while the primitive jawless fish have seven. The vertebrate ancestor no doubt had more arches than this, as some of their relatives have more than 50 pairs of gills. In amphibians and some primitive fishes, the larvae bear external gills. These are reduced in adulthood, their function taken over by the gills proper in fishes, some amphibians retain the external larval gills in adulthood, the complex internal gill system as seen in fish apparently being irrevocably lost very early in the evolution of tetrapods
16.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
17.
Thrombin
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Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the clotting process, thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872, thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X. The activity of factor Xa is greatly enhanced by binding to activated Factor V, prothrombin is produced in the liver and is co-translationally modified in a vitamin K-dependent reaction that converts ten glutamic acids on prothrombin to gamma-carboxyglutamic acid. In the presence of calcium, the Gla residues promote the binding of prothrombin to phospholipid bilayers, deficiency of vitamin K or administration of the anticoagulant warfarin inhibits the production of gamma-carboxyglutamic acid residues, slowing the activation of the coagulation cascade. In human adults, the blood level of antithrombin activity has been measured to be around 1.1 units/mL. Newborn levels of thrombin steadily increase after birth to normal adult levels, from a level of around 0.5 units/mL1 day after birth. In the blood coagulation pathway, thrombin acts to convert factor XI to XIa, VIII to VIIIa, V to Va, fibrinogen to fibrin, Factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between lysine and glutamine residues in fibrin. The covalent bonds increase the stability of the fibrin clot, as part of its activity in the coagulation cascade, thrombin also promotes platelet activation and aggregation via activation of protease-activated receptors on the cell membrane of the platelet. Thrombin bound to thrombomodulin activates protein C, an inhibitor of the coagulation cascade, the activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin, an integral membrane protein expressed by endothelial cells. Activated protein C inactivates factors Va and VIIIa, binding of activated protein C to protein S leads to a modest increase in its activity. Thrombin is also inactivated by antithrombin, a protease inhibitor. The molecular weight of prothrombin is approximately 72,000 Da, the catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36,000 Da. Structurally, it is a member of the large PA clan of proteases, prothrombin is composed of four domains, an N-terminal Gla domain, two kringle domains and a C-terminal trypsin-like serine protease domain. Factor Xa with factor V as a cofactor leads to cleavage of the Gla, as is the case for all serine proteases, prothrombin is converted to active thrombin by proteolysis of an internal peptide bond, exposing a new N-terminal Ile-NH3. However, binding of the fragment of thrombomodulin appears to allosterically promote the active conformation of thrombin by inserting this N-terminal region. The thrombin gene is located on the eleventh chromosome, prothrombin G20210A is not usually accompanied by other factor mutations. The gene may be inherited heterozygous, or much more rarely, homozygous, homozygous mutations increase the risk of thrombosis more than heterozygous mutations, but the relative increased risk is not well documented
18.
Platelet
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Platelets, also called thrombocytes, are a component of blood whose function is to stop bleeding by clumping and clotting blood vessel injuries. Platelets have no nucleus, they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow. These unactivated platelets are biconvex discoid structures, 2–3 µm in greatest diameter, platelets are found only in mammals, whereas in other animals thrombocytes circulate as intact mononuclear cells. On a stained blood smear, platelets appear as purple spots. The smear is used to examine platelets for size, shape, qualitative number, the ratio of platelets to red blood cells in a healthy adult is 1,10 to 1,20. The main function of platelets is to contribute to hemostasis, the process of stopping bleeding at the site of interrupted endothelium and they gather at the site and unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium, adhesion, second, they change shape, turn on receptors and secrete chemical messengers, activation. Third, they connect to each other through receptor bridges, aggregation, formation of this platelet plug is associated with activation of the coagulation cascade with resultant fibrin deposition and linking. These processes may overlap, the spectrum is from a predominantly platelet plug, or white clot to a predominantly fibrin clot, the final result is the clot. Some would add the subsequent clot retraction and platelet inhibition as fourth and fifth steps to the completion of the process, low platelet concentration is thrombocytopenia and is due to either decreased production or increased destruction. Elevated platelet concentration is thrombocytosis and is either congenital, reactive, or due to unregulated production, a disorder of platelet function is a thrombocytopathy. An arterial thrombus may partially obstruct blood flow, causing downstream ischemia, or may completely obstruct it, george Gulliver in 1841 drew pictures of platelets using the twin lens microscope invented in 1830 by Joseph Jackson Lister. This microscope improved resolution sufficiently to make it possible to see platelets for the first time, william Addison in 1842 drew pictures of a platelet-fibrin clot. Lionel Beale in 1864 was the first to publish a drawing showing platelets, max Schultze in 1865 described what he called spherules, which he noted were much smaller than red blood cells, occasionally clumped, and were sometimes found in collections of fibrin material. Queens College, Birmingham physician Dr Richard Hill Norris was the first to describe the action of platelets in 1880, giulio Bizzozero in 1882 studied the blood of amphibians microscopically in vivo. He named Schultzs spherules piastrine, little plates, william Osler observed them and, in published lectures in 1886, called them a third corpuscle and a blood plaque and described them as a colorless protoplasmic disc. Thrombocytes are cells found in the blood of non-mammalian vertebrates and they are the functional equivalents of platelets, but circulate as intact mononuclear cells, and are not simply cytoplasmic fragments of bone marrow megakaryocytes. In some contexts, the thrombus is used interchangeably with the word clot
19.
Endothelium
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It is a thin layer of simple squamous cells called endothelial cells. Endothelial cells in contact with blood are called vascular endothelial cells. Vascular endothelial cells line the entire system, from the heart to the smallest capillaries. These cells have unique functions in vascular biology and these functions include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the surfaces of the heart chambers is called endocardium. Both blood and lymphatic capillaries are composed of a layer of endothelial cells called a monolayer. In straight sections of a vessel, vascular endothelial cells typically align. Many considered the endothelium a specialized epithelial tissue, excessive or prolonged increases in permeability of the endothelial monolayer, as in cases of chronic inflammation, may lead to tissue edema/swelling. The most prevailing mechanism of endothelial dysfunction is an increase in reactive oxygen species, the signalling protein ERK5 is essential for maintaining normal endothelial cell function
20.
Fibroblast
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A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals, fibroblasts and fibrocytes are two states of the same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to both forms fibroblasts. The suffix -blast is used in biology to denote a stem cell or a cell in an activated state of metabolism. Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and this remarkable behavior may lead to discomfort in the rare event that they stagnate there excessively. The main function of fibroblasts is to maintain the integrity of connective tissues by continuously secreting precursors of the extracellular matrix. Fibroblasts secrete the precursors of all the components of the matrix, primarily the ground substance. The composition of the extracellular matrix determines the properties of connective tissues. Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme, thus they express the intermediate filament protein vimentin, a feature used as a marker to distinguish their mesodermal origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time, in certain situations epithelial cells can give rise to fibroblasts, a process called epithelial-mesenchymal transition. This process is seen in many situations, as well as in wound healing. Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli, active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibrocytes are smaller, spindle shaped, and have a reduced rough endoplasmic reticulum, although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Fibroblasts make collagens, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in the extracellular matrix, growing individuals fibroblasts are dividing and synthesizing ground substance. Tissue damage stimulates fibrocytes and induces the mitosis of fibroblasts, fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. While epithelial cells form the lining of body structures, it is fibroblasts, the life span of a fibroblast, as measured in chick embryos, is 57 ±3 days. Besides their commonly known role as components, fibroblasts play a critical role in an immune response to a tissue injury. They are early players in initiating inflammation in the presence of invading microorganisms and they induce chemokine synthesis through the presentation of receptors on their surface
21.
Capillary action
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Capillary action is the ability of a liquid to flow in narrow spaces without the assistance of, or even in opposition to, external forces like gravity. It occurs because of forces between the liquid and surrounding solid surfaces. If the diameter of the tube is sufficiently small, then the combination of surface tension, the first recorded observation of capillary action was by Leonardo da Vinci. A former student of Galileo, Niccolò Aggiunti, was said to have investigated capillary action, boyle then reported an experiment in which he dipped a capillary tube into red wine and then subjected the tube to a partial vacuum. Some thought that liquids rose in capillaries because air couldnt enter capillaries as easily as liquids, others thought that the particles of liquid were attracted to each other and to the walls of the capillary. They derived the Young–Laplace equation of capillary action, by 1830, the German mathematician Carl Friedrich Gauss had determined the boundary conditions governing capillary action. In 1871, the British physicist William Thomson determined the effect of the meniscus on a liquids vapor pressure—a relation known as the Kelvin equation, German physicist Franz Ernst Neumann subsequently determined the interaction between two immiscible liquids. Albert Einsteins first paper, which was submitted to Annalen der Physik in 1900, was on capillarity, a common apparatus used to demonstrate the first phenomenon is the capillary tube. When the lower end of a glass tube is placed in a liquid, such as water. Adhesion occurs between the fluid and the inner wall pulling the liquid column up until there is a sufficient mass of liquid for gravitational forces to overcome these intermolecular forces. So, a tube will draw a liquid column higher than a wider tube will. Capillary action is essential for the drainage of constantly produced tear fluid from the eye, wicking is the absorption of a liquid by a material in the manner of a candle wick. Paper towels absorb liquid through capillary action, allowing a fluid to be transferred from a surface to the towel, the small pores of a sponge act as small capillaries, causing it to absorb a large amount of fluid. Some textile fabrics are said to use capillary action to wick sweat away from the skin and these are often referred to as wicking fabrics, after the capillary properties of candle and lamp wicks. Capillary action is observed in thin layer chromatography, in which a solvent moves vertically up a plate via capillary action, in this case the pores are gaps between very small particles. Capillary action draws ink to the tips of fountain pen nibs from a reservoir or cartridge inside the pen, in hydrology, capillary action describes the attraction of water molecules to soil particles. Capillary action is responsible for moving groundwater from wet areas of the soil to dry areas, differences in soil potential drive capillary action in soil. Thus the thinner the space in which the water can travel, for a water-filled glass tube in air at standard laboratory conditions, γ =0.0728 N/m at 20 °C, ρ =1000 kg/m3, and g =9.81 m/s2
22.
Angiogenesis
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Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. The first vessels in the embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a step in the transition of tumors from a benign state to a malignant one. Sprouting angiogenesis was the first identified form of angiogenesis and it occurs in several well-characterized stages. First, biological signals known as growth factors activate receptors on endothelial cells present in pre-existing blood vessels. Second, the endothelial cells begin to release enzymes called proteases that degrade the basement membrane to allow endothelial cells to escape from the original vessel walls. The endothelial cells then proliferate into the matrix and form solid sprouts connecting neighboring vessels. As sprouts extend toward the source of the stimulus, endothelial cells migrate in tandem. These sprouts then form loops to become a full-fledged vessel lumen as cells migrate to the site of angiogenesis, sprouting occurs at a rate of several millimeters per day, and enables new vessels to grow across gaps in the vasculature. It is markedly different from splitting angiogenesis because it forms new vessels as opposed to splitting existing vessels. By intussusception, also known as splitting angiogenesis, a new vessel is created by splitting of an existing blood vessel in two. Intussusception was first observed in neonatal rats, in this type of vessel formation, the capillary wall extends into the lumen to split a single vessel in two. There are four phases of intussusceptive angiogenesis, first, the two opposing capillary walls establish a zone of contact. Second, the endothelial cell junctions are reorganized and the vessel bilayer is perforated to allow growth factors, third, a core is formed between the 2 new vessels at the zone of contact that is filled with pericytes and myofibroblasts. These cells begin laying collagen fibers into the core to provide a matrix for growth of the vessel lumen. Finally, the core is fleshed out with no alterations to the basic structure, intussusception is important because it is a reorganization of existing cells. It allows a vast increase in the number of capillaries without an increase in the number of endothelial cells
23.
Tissue engineering
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Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological tissues. Tissue engineering involves the use of a scaffold for the formation of new viable tissue for a medical purpose, while it was once categorized as a sub-field of biomaterials, having grown in scope and importance it can be considered as a field in its own. While most definitions of tissue engineering cover a range of applications. Often, the tissues involved require certain mechanical and structural properties for proper functioning, the term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system. Tissue engineering has also defined as understanding the principles of tissue growth. Powerful developments in the field of tissue engineering have yielded a novel set of tissue replacement parts. In 2003, the NSF published a report entitled The Emergence of Tissue Engineering as a Research Field, bioartificial windpipe, The first procedure of regenerative medicine of an implantation of a bioartificial organ. In vitro meat, Edible artificial animal muscle tissue cultured in vitro, bioartificial liver device, several research efforts have produced hepatic assist devices utilizing living hepatocytes. Artificial pancreas, research involves using islet cells to produce and regulate insulin, Artificial bladders, Anthony Atala has successfully implanted artificially grown bladders into seven out of approximately 20 human test subjects as part of a long-term experiment. Cartilage, lab-grown tissue was used to repair knee cartilage. Scaffold-free cartilage, Cartilage generated without the use of exogenous scaffold material, in this methodology, all material in the construct is cellular or material produced directly by the cells themselves. Artificial bone marrow Artificial bone Laboratory-grown penis Oral mucosa tissue engineering Foreskin Tissue engineering utilizes living cells as engineering materials, examples include using living fibroblasts in skin replacement or repair, cartilage repaired with living chondrocytes, or other types of cells used in other ways. Cells became available as engineering materials when scientists at Geron Corp. discovered how to extend telomeres in 1998, before this, laboratory cultures of healthy, noncancerous mammalian cells would only divide a fixed number of times, up to the Hayflick limit, before dying. From fluid tissues such as blood, cells are extracted by bulk methods, from solid tissues, extraction is more difficult. Usually the tissue is minced, and then digested with the enzymes trypsin or collagenase to remove the matrix that holds the cells. After that, the cells are free floating, and extracted using centrifugation or apheresis, digestion with trypsin is very dependent on temperature. Higher temperatures digest the matrix faster, but create more damage, collagenase is less temperature dependent, and damages fewer cells, but takes longer and is a more expensive reagent. Cells are often categorized by their source Autologous cells are obtained from the individual to which they will be reimplanted
24.
Acute-phase protein
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Acute-phase proteins are a class of proteins whose plasma concentrations increase or decrease in response to inflammation. This response is called the acute-phase reaction, in response to injury, local inflammatory cells secrete a number of cytokines into the bloodstream, most notable of which are the interleukins IL1, IL6 and IL8, and TNFα. The liver responds by producing a number of acute-phase reactants. At the same time, the production of a number of proteins is reduced. Increased acute phase proteins from the liver may also contribute to the promotion of sepsis, positive acute-phase proteins serve different physiological functions for the immune system. Some act to destroy or inhibit growth of microbes, e. g. C-reactive protein, mannose-binding protein, complement factors, ferritin, ceruloplasmin, serum amyloid A, others give negative feedback on the inflammatory response, e. g. serpins. Alpha 2-macroglobulin and coagulation factors affect coagulation, mainly stimulating it and this pro-coagulant effect may limit infection by trapping pathogens in local blood clots. Also, some products of the system can contribute to the innate immune system by their ability to increase vascular permeability. Negative acute-phase proteins decrease in inflammation, examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as markers of inflammation, the physiological role of decreased synthesis of such proteins is generally to save amino acids for producing positive acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptors, measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation in both medical and veterinary clinical pathology. It correlates with the erythrocyte sedimentation rate, however not always directly and this is due to the ESR being largely dependent on elevation of fibrinogen, an acute phase reactant with a half-life of approximately one week. This protein will therefore remain higher for longer despite removal of the inflammatory stimuli, in contrast, C-reactive protein rises rapidly and can quickly return to within the normal range if treatment is employed. For example, in active systemic lupus erythematosus, one may find a raised ESR and they may also indicate liver failure. Wikipedia, MeSH D12. 776#MeSH D12.776.124.050 --- acute-phase proteins Acute-Phase Proteins at the US National Library of Medicine Medical Subject Headings
25.
Inflammation
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The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity. Too little inflammation could lead to tissue destruction by the harmful stimulus. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, Inflammation is therefore normally closely regulated by the body. Inflammation can be classified as acute or chronic. Acute inflammation is the response of the body to harmful stimuli and is achieved by the increased movement of plasma. A series of biochemical events propagates and matures the inflammatory response, involving the vascular system, the immune system. Inflammation is not a synonym for infection, Inflammation on the other hand describes purely the bodys immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix -itis are sometimes described as referring to infection. There are also situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis. Acute inflammation is a process, usually appearing within a few minutes or hours. It involves a coordinated and systemic mobilisation response locally of various immune, endocrine, in a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. It is characterized by five signs, An acronym that may be used to remember the key symptoms is PRISH, for pain, redness, immobility, swelling. Loss of function has multiple causes, Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings. PAMPs are compounds that are associated with pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage, at the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness and increased heat, increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling. Some of the released mediators such as increase the sensitivity to pain
26.
Hepatocyte
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A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 70-85% of the livers mass, the typical volume of a hepatocyte is 3.4 x 10−9 cm3. Smooth endoplasmic reticulum is abundant in hepatocytes, whereas most cells in the body have only small amounts, hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, and basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes. Brown lipofuscin granules are observed together with irregular unstained areas of cytoplasm. The average life span of the hepatocyte is 5 months, they are able to regenerate, hepatocyte nuclei are round with dispersed chromatin and prominent nucleoli. Anisokaryosis is common and often reflects tetraploidy and other degrees of polyploidy, hepatocytes are organised into plates separated by vascular channels, an arrangement supported by a reticulin network. The hepatocyte plates are one cell thick in mammals and two cells thick in the chicken, sinusoids display a discontinuous, fenestrated endothelial cell lining. The endothelial cells have no basement membrane and are separated from the hepatocytes by the space of Disse, kupffer cells are scattered between endothelial cells, they are part of the reticuloendothelial system and phagocytose spent erythrocytes. Stellate cells store vitamin A and produce extracellular matrix and collagen, the hepatocyte is a cell in the body that manufactures serum albumin, fibrinogen, and the prothrombin group of clotting factors. It is the site for the synthesis of lipoproteins, ceruloplasmin, transferrin, complement. Hepatocytes manufacture their own proteins and intracellular enzymes. Synthesis of proteins is by the endoplasmic reticulum, and both the rough and smooth endoplasmic reticulum are involved in secretion of the proteins formed. The endoplasmic reticulum is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and glycerol. Hepatocytes also synthesize apoproteins with which they then assemble and export lipoproteins, the liver is also the main site in the body for gluconeogenesis, the formation of carbohydrates from precursors such as alanine, glycerol, and oxaloacetate. The liver receives many lipids from the circulation and metabolizes chylomicron remnants. It also synthesizes cholesterol from acetate and further synthesizes bile salts, the liver is the sole site of bile salts formation. Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs, and insecticides, the drainage of the intestinal venous blood into the liver requires efficient detoxification of miscellaneous absorbed substances to maintain homeostasis and protect the body against ingested toxins. One of the functions of hepatocytes is to modify ammonia into urea for excretion
27.
Megakaryocyte
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A megakaryocyte is a large bone marrow cell with a lobulated nucleus responsible for the production of blood thrombocytes, which are necessary for normal blood clotting. Megakaryocytes normally account for 1 out of 10,000 bone marrow cells, owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte. In general, megakaryocytes are 10 to 15 times larger than a red blood cell. During its maturation, the megakaryocyte grows in size and replicates its DNA without cytokinesis in a process called endomitosis. As a result, the nucleus of the megakaryocyte can become large and lobulated. In some cases, the nucleus may contain up to 64N DNA, the cytoplasm, just as the platelets that bud off from it, contains α-granula and Dense bodies. Megakaryocytes are derived from stem cell precursor cells in the bone marrow. They are produced primarily by the liver, kidney, spleen and these multipotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. The primary signal for megakaryocyte production is thrombopoietin or TPO, TPO is sufficient but not absolutely necessary for inducing differentiation of progenitor cells in the bone marrow towards a final megakaryocyte phenotype. Other molecular signals for megakaryocyte differentiation include GM-CSF, IL-3, IL-6, IL-11, chemokines. the megakaryocyte develops through the following lineage, CFU-Me -> megakaryoblast -> promegakaryocyte -> megakaryocyte. The cell eventually reaches megakaryocyte stage and loses its ability to divide, however, it is still able to replicate its DNA and continue development, becoming polyploid. The cytoplasm continues to expand and the DNA complement can increase up to 64N in human, once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets. The maturation process occurs via endomitotic synchronous replication whereby the cytoplasmic volume enlarges as the number of chromosomes multiplies without cellular division, the cell ceases its growth at 4N, 8N or 16N, becomes granular, and begins to produce platelets. Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes, platelets are held within these internal membranes within the cytoplasm of megakaryocytes. There are two proposed mechanisms for platelet release, in one scenario, these proto-platelet processes break up explosively to become platelets. Alternatively, the cell may form platelet ribbons into blood vessels, the ribbons are formed via pseudopodia and they are able to continuously emit platelets into circulation. In either scenario, each of these processes can give rise to 2000-5000 new platelets upon breakup. Overall, 2/3 of these newly produced platelets will remain in circulation while 1/3 will be sequestered by the spleen, after budding off platelets, what remains is mainly the cell nucleus
28.
Protein trimer
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In biochemistry, a trimer is a macromolecular complex formed by three, usually non-covalently bound, macromolecules like proteins or nucleic acids. A homo-trimer would be formed by three identical molecules, a hetero-trimer would be formed by three different macromolecules. Collagen is an example of homo-trimeric protein, porins usually arrange themselves in membranes as trimers
29.
Polypeptide chains
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Peptides are biologically occurring short chains of amino acid monomers linked by peptide bonds. The covalent chemical bonds are formed when the group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a peptide bond, followed by tripeptides, tetrapeptides. A polypeptide is a long, continuous, and unbranched peptide chain, hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc. Peptides are distinguished from proteins on the basis of size, all peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide. Ribosomal peptides Ribosomal peptides are synthesized by translation of mRNA and they are often subjected to proteolysis to generate the mature form. These function, typically in higher organisms, as hormones and signaling molecules, some organisms produce peptides as antibiotics, such as microcins. Since they are translated, the amino acid residues involved are restricted to those utilized by the ribosome, however, these peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are linear, although lariat structures have been observed, more exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom. Nonribosomal peptides Nonribosomal peptides are assembled by enzymes that are specific to each peptide, the most common non-ribosomal peptide is glutathione, which is a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in organisms, plants. These complexes are often out in a similar fashion. These peptides are often cyclic and can have highly complex cyclic structures, since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion, Peptones See also Tryptone Peptones are derived from animal milk or meat digested by proteolysis. In addition to containing small peptides, the material includes fats, metals, salts, vitamins. Peptones are used in nutrient media for growing bacteria and fungi, Peptide fragments Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Peptides received prominence in molecular biology for several reasons, the first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest and these will then be used to make antibodies in a rabbit or mouse against the protein
30.
Alternative splicing
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Alternative splicing, or differential splicing, is a regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions. Notably, alternative splicing allows the human genome to direct the synthesis of many more proteins than would be expected from its 20,000 protein-coding genes, there are numerous modes of alternative splicing observed, of which the most common is exon skipping. In this mode, an exon may be included in mRNAs under some conditions or in particular tissues. The production of alternatively spliced mRNAs is regulated by a system of trans-acting proteins that bind to cis-acting sites on the transcript itself. Such proteins include splicing activators that promote the usage of a splice site. Mechanisms of alternative splicing are highly variable, and new examples are constantly being found, abnormal variations in splicing are also implicated in disease, a large proportion of human genetic disorders result from splicing variants. Abnormal splicing variants are thought to contribute to the development of cancer. Alternative splicing was first observed in 1977, the Adenovirus produces five primary transcripts early in its infectious cycle, prior to viral DNA replication, and an additional one later, after DNA replication begins. The early primary transcripts continue to be produced after DNA replication begins, the additional primary transcript produced late in infection is large and comes from 5/6 of the 32kb adenovirus genome. This is much larger than any of the individual adenovirus mRNAs present in infected cells, researchers found that the primary RNA transcript produced by adenovirus type 2 in the late phase was spliced in many different ways, resulting in mRNAs encoding different viral proteins. In addition, the primary transcript contained multiple polyadenylation sites, giving different 3’ ends for the processed mRNAs, in 1981, the first example of alternative splicing in a transcript from a normal, endogenous gene was characterized. The gene encoding the thyroid hormone calcitonin was found to be spliced in mammalian cells. The primary transcript from this gene contains 6 exons, the calcitonin mRNA contains exons 1–4, another mRNA is produced from this pre-mRNA by skipping exon 4, and includes exons 1–3,5, and 6. It encodes a protein known as CGRP, examples of alternative splicing in immunoglobin gene transcripts in mammals were also observed in the early 1980s. Since then, alternative splicing has been found to be ubiquitous in eukaryotes, the record-holder for alternative splicing is a D. melanogaster gene called Dscam, which could potentially have 38,016 splice variants. Five basic modes of alternative splicing are generally recognized, exon skipping or cassette exon, in this case, an exon may be spliced out of the primary transcript or retained. This is the most common mode in mammalian pre-mRNAs, mutually exclusive exons, One of two exons is retained in mRNAs after splicing, but not both
31.
Transcription (biology)
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Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language, during transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the general steps, RNA polymerase, together with one or more general transcription factors. RNA polymerase creates a bubble, which separates the two strands of the DNA helix. This is done by breaking the bonds between complementary DNA nucleotides. RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand, hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand. If the cell has a nucleus, the RNA may be further processed and this may include polyadenylation, capping, and splicing. The RNA may remain in the nucleus or exit to the cytoplasm through the pore complex. The stretch of DNA transcribed into an RNA molecule is called a transcription unit, if the gene encodes a protein, the transcription produces messenger RNA, the mRNA, in turn, serves as a template for the proteins synthesis through translation. Alternatively, the gene may encode for either non-coding RNA, ribosomal RNA, transfer RNA. Overall, RNA helps synthesize, regulate, and process proteins, in virology, the term may also be used when referring to mRNA synthesis from an RNA molecule. For instance, the genome of a negative-sense single-stranded RNA virus may be template for a positive-sense single-stranded RNA and this is because the positive-sense strand contains the information needed to translate the viral proteins for viral replication afterwards. This process is catalyzed by a viral RNA replicase, the regulatory sequence before the coding sequence is called the five prime untranslated region, the sequence after the coding sequence is called the three prime untranslated region. As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil in all instances where thymine would have occurred in a DNA complement, only one of the two DNA strands serve as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3 end to the 5 end during transcription. The complementary RNA is created in the direction, in the 5 →3 direction. This directionality is because RNA polymerase can only add nucleotides to the 3 end of the growing mRNA chain and this use of only the 3 →5 DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This also removes the need for an RNA primer to initiate RNA synthesis, the non-template strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript
32.
Translation (biology)
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In molecular biology and genetics, translation is the process in which ribosomes in a cells cytoplasm create proteins, following transcription of DNA to RNA in the cells nucleus. The entire process is a part of gene expression, in translation, messenger RNA is decoded by a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide. The polypeptide later folds into a protein and performs its functions in the cell. The ribosome facilitates decoding by inducing the binding of complementary tRNA anticodon sequences to mRNA codons, the tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is read by the ribosome. Translation proceeds in three phases, Initiation, The ribosome assembles around the target mRNA, the first tRNA is attached at the start codon. Elongation, The tRNA transfers an amino acid to the corresponding to the next codon. The ribosome then moves to the next mRNA codon to continue the process, termination, When a stop codon is reached, the ribosome releases the polypeptide. In bacteria, translation occurs in the cytoplasm, where the large, in eukaryotes, translation occurs in the cytosol or across the membrane of the endoplasmic reticulum in a process called vectorial synthesis. Many types of transcribed RNA, such as transfer RNA, ribosomal RNA, a number of antibiotics act by inhibiting translation. These include anisomycin, cycloheximide, chloramphenicol, tetracycline, streptomycin, erythromycin, prokaryotic ribosomes have a different structure from that of eukaryotic ribosomes, and thus antibiotics can specifically target bacterial infections without any harm to a eukaryotic hosts cells. The basic process of production is addition of one amino acid at a time to the end of a protein. This operation is performed by a ribosome, a ribosome is made up of two subunits, a small subunit and a large subunit. These subunits come together before translation of mRNA into a protein to provide a location for translation to be carried out, the choice of amino acid type to add is determined by an mRNA molecule. Each amino acid added is matched to a three nucleotide subsequence of the mRNA, for each such triplet possible, the corresponding amino acid is accepted. The successive amino acids added to the chain are matched to successive nucleotide triplets in the mRNA, in this way the sequence of nucleotides in the template mRNA chain determines the sequence of amino acids in the generated amino acid chain. Addition of an amino acid occurs at the C-terminus of the peptide, the mRNA carries genetic information encoded as a ribonucleotide sequence from the chromosomes to the ribosomes. The ribonucleotides are read by translational machinery in a sequence of nucleotide triplets called codons, each of those triplets codes for a specific amino acid. The ribosome molecules translate this code to a sequence of amino acids
33.
Interleukin 6
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Interleukin 6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene, interleukin 6 is secreted by T cells and macrophages to stimulate immune response, e. g. during infection and after trauma, especially burns or other tissue damage leading to inflammation. IL-6 also plays a role in fighting infection, as IL-6 has been shown in mice to be required for resistance against bacterium Streptococcus pneumoniae, in addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6s role as an anti-inflammatory cytokine is mediated through its effects on TNF-alpha and IL-1. IL-6 is an important mediator of fever and of the phase response. It is capable of crossing the barrier and initiating synthesis of PGE2 in the hypothalamus. In muscle and fatty tissue, IL-6 stimulates energy mobilization that leads to increased body temperature, IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns. These PAMPs bind to an important group of molecules of the innate immune system, called pattern recognition receptors. These are present on the surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production. IL-6 is also essential for growth and is found in many supplemental cloning media such as briclone. Inhibitors of IL-6 are used to treat postmenopausal osteoporosis, IL-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP. Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories, IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow. It supports the growth of B cells and is antagonistic to regulatory T cells, when psychologically stressed, the human body produces stress hormones like cortisol, which are able to trigger interleukin-6 release into the circulation. Interleukin-6s antagonistic position to T-Cells, seems to be at least partly mediated by the effect of PGE2 on the signaling function of T-Cells. Therefore IL-6 seems to play a role in the process of acute or chronic stress suppressing the immune system. High levels of IL-6 in cancer-patients or in children with encephalitis could therefore be explained by the levels of psychological stress these diseases trigger in the patients minds. IL-6 is also considered a myokine, a cytokine produced from muscle and it is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation
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Translation
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Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. While interpreting—the facilitating of oral or sign-language communication between users of different languages—antedates writing, translation began only after the appearance of written literature, there exist partial translations of the Sumerian Epic of Gilgamesh into Southwest Asian languages of the second millennium BCE. Translators always risk inappropriate spill-over of source-language idiom and usage into the target-language translation, on the other hand, spill-overs have imported useful source-language calques and loanwords that have enriched the target languages. Indeed, translators have helped substantially to shape the languages into which they have translated, because of the laboriousness of translation, since the 1940s engineers have sought to automate translation or to mechanically aid the human translator. The rise of the Internet has fostered a world-wide market for services and has facilitated language localization. Translation studies systematically study the theory and practice of translation, the English word translation derives from the Latin word translatio, which comes from trans, across + ferre, to carry or to bring. Thus translatio is a carrying across or a bringing across, in this case, the Germanic languages and some Slavic languages have calqued their words for the concept of translation on translatio. The Romance languages and the remaining Slavic languages have derived their words for the concept of translation from an alternative Latin word, traductio, the Ancient Greek term for translation, μετάφρασις, has supplied English with metaphrase — as contrasted with paraphrase. Metaphrase corresponds, in one of the more recent terminologies, to formal equivalence, nevertheless, metaphrase and paraphrase may be useful as ideal concepts that mark the extremes in the spectrum of possible approaches to translation. Discussions of the theory and practice of translation reach back into antiquity, the ancient Greeks distinguished between metaphrase and paraphrase. Literally graceful, it were an injury to the author that they should be changed, Dryden cautioned, however, against the license of imitation, i. e. of adapted translation, When a painter copies from the life. He has no privilege to alter features and lineaments, despite occasional theoretical diversity, the actual practice of translation has hardly changed since antiquity. The grammatical differences between languages and free-word-order languages have been no impediment in this regard. The particular syntax characteristics of a source language are adjusted to the syntactic requirements of the target language. When a target language has lacked terms that are found in a language, translators have borrowed those terms. However, due to shifts in ecological niches of words, an etymology is sometimes misleading as a guide to current meaning in one or the other language. For example, the English actual should not be confused with the cognate French actuel, the Polish aktualny, the Swedish aktuell, the translators role as a bridge for carrying across values between cultures has been discussed at least since Terence, the 2nd-century-BCE Roman adapter of Greek comedies. The translators role is, however, by no means a passive, mechanical one, the main ground seems to be the concept of parallel creation found in critics such as Cicero
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Endoplasmic reticulum
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The endoplasmic reticulum is a type of organelle in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the nuclear membrane. The endoplasmic reticulum occurs in most types of cells, including Giardia. There are two types of endoplasmic reticulum, rough and smooth, the outer face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is especially prominent in such as hepatocytes. The smooth endoplasmic reticulum lacks ribosomes and functions in lipid manufacture and metabolism, the production of steroid hormones, the smooth ER is especially abundant in mammalian liver and gonad cells. The lacy membranes of the endoplasmic reticulum were first seen in 1945 using electron microscopy, the lacy membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Brody Meskers and Ernest F. Fullam, using electron microscopy. The word reticulum, which network, was applied to describe this fabric of membranes. The general structure of the reticulum is a network of membranes called cisternae. These sac-like structures are held together by the cytoskeleton, the phospholipid membrane encloses the cisternal space, which is continuous with the perinuclear space but separate from the cytosol. The functions of the reticulum can be summarized as the synthesis and export of proteins and membrane lipids. The quantity of both rough and smooth endoplasmic reticulum in a cell can slowly interchange from one type to the other, transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes, the surface of the rough endoplasmic reticulum is studded with protein-manufacturing ribosomes giving it a rough appearance. The binding site of the ribosome on the endoplasmic reticulum is the translocon. However, the ribosomes are not a part of this organelles structure as they are constantly being bound. A ribosome only binds to the RER once a specific protein-nucleic acid complex forms in the cytosol and this special complex forms when a free ribosome begins translating the mRNA of a protein destined for the secretory pathway. The first 5-30 amino acids polymerized encode a signal peptide, a message that is recognized. Translation pauses and the complex binds to the RER translocon where translation continues with the nascent protein forming into the RER lumen and/or membrane
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Disulfide
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In chemistry, a disulfide refers to a functional group with the structure R–S–S–R. The linkage is called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. The connection is a persulfide, in analogy to its congener, peroxide, in inorganic chemistry disulfide usually refers to the corresponding anion S2−2, for example in disulfur dichloride. The disulfide bonds are strong, with a bond dissociation energy of 60 kcal/mol. However, being about 40% weaker than C–C and C–H bonds, rotation about the S–S axis is subject to a low barrier. Disulfides show a preference for dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant, disulfides where the two R groups are the same are called symmetric, examples being diphenyl disulfide and dimethyl disulfide. When the two R groups are not identical, the compound is said to be an asymmetric or mixed disulfide, by comparison, the standard reduction potential for ferrodoxins is about −430 mV. Disulfide bonds are formed from the oxidation of sulfhydryl groups. The transformation is depicted as follows,2 RSH ⇌ RS–SR +2 H+ +2 e− A variety of oxidants promote this reaction including air, such reactions are thought to proceed via sulfenic acid intermediates. In the laboratory, iodine in the presence of base is employed to oxidize thiols to disulfides. Several metals, such as copper and iron complexes affect this reaction, the alkylation of alkali metal di- and polysulfides gives disulfides. Thiokol polymers arise when sodium polysulfide is treated with an alkyl dihalide, in the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides. These reactions are often unselective but can be optimized for specific applications, many specialized methods have been developed for forming disulfides, usually for applications in organic synthesis. A variety of reductants can be used, furthermore, it is often not needed to remove TCEP before modification of protein thiols. In organic synthesis, hydride agents are employed for scission of disulfides. The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, meanwhile, a new disulfide bond forms between the attacking thiolate and the original sulfur atom. Thiolates, not thiols, attack disulfide bonds, hence, thiol–disulfide exchange is inhibited at low pH where the protonated thiol form is favored relative to the deprotonated thiolate form
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Golgi apparatus
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The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. It was identified in 1897 by the Italian scientist Camillo Golgi, part of the cellular endomembrane system, the Golgi apparatus packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. The Golgi apparatus resides at the intersection of the secretory, lysosomal, owing to its large size and distinctive structure, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system, after first observing it under his microscope, he termed the structure the internal reticular apparatus. Some doubted the discovery at first, arguing that the appearance of the structure was merely an illusion created by the observation technique used by Golgi. With the development of modern microscopes in the 20th century, the discovery was confirmed, early references to the Golgi referred to it by various names including the Golgi–Holmgren apparatus, Golgi–Holmgren ducts, and Golgi–Kopsch apparatus. The term Golgi apparatus was used in 1910 and first appeared in the literature in 1913. Among eukaryotes, the localization of the Golgi apparatus differs. In mammals, a single Golgi apparatus complex is located near the cell nucleus. Tubular connections are responsible for linking the stacks together, localization and tubular connections of the Golgi apparatus are dependent on microtubules. If microtubules are experimentally depolymerized, then the Golgi apparatus loses connections, in yeast, multiple Golgi apparatuses are scattered throughout the cytoplasm. In plants, Golgi stacks are not concentrated at the centrosomal region, organization of the plant Golgi depends on actin cables and not microtubules. The common feature among Golgi is that they are adjacent to endoplasmic reticulum exit sites, in most eukaryotes, the Golgi apparatus is made up of a series of compartments consisting of two main networks, the cis Golgi network and the trans Golgi network. The CGN is a collection of fused, flattened membrane-enclosed disks known as cisternae, a mammalian cell typically contains 40 to 100 stacks. Between four and eight cisternae are usually present in a stack, however and this collection of cisternae is broken down into cis, medial, and trans compartments. The TGN is the final structure, from which proteins are packaged into vesicles destined to lysosomes, secretory vesicles. The TGN is usually positioned adjacent to the stacks of the Golgi apparatus, the TGN may act as an early endosome in yeast and plants. There are structural and organizational differences in the Golgi apparatus among eukaryotes, in some yeasts, Golgi stacking is not observed
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N-linked glycosylation
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N-linked glycosylation, is the attachment of the sugar molecule oligosaccharide known as glycan to a nitrogen atom, in a process called N-glycosylation, studied in biochemistry. This type of linkage is important for both the structure and function of some eukaryotic proteins, the N-linked glycosylation process occurs in eukaryotes and widely in archaea, but very rarely in bacteria. The nature of N-linked glycans attached to a glycoprotein is determined by the protein, different species synthesize different types of N-linked glycan. There are two types of bonds involved in a glycoprotein, bonds between the residues in the glycan and the linkage between the glycan chain and the protein molecule. The sugar moieties are linked to one another in the chain via glycosidic bonds. These bonds are formed between carbon 1 and 4 of the sugar molecules. The formation of glycosidic bond is energetically unfavourable, therefore the reaction is coupled to the hydrolysis of two ATP molecules, on the other hand, the attachment of a glycan residue to a protein requires the recognition of a consensus sequence. N-linked glycans are almost always attached to the atom of an asparagine side chain that is present as a part of Asn-X-Ser/Thr consensus sequence. In animal cells, the attached to the asparagine is almost inevitably N-acetylglucosamine. This β-linkage is similar to glycosidic bond between the sugar moieties in the structure as described above. Instead of being attached to a hydroxyl group, the anomeric carbon atom is attached to an amide nitrogen. The energy required for this comes from the hydrolysis of a pyrophosphate molecule. Subsequent processing and modification of the chain is carried out in the Golgi apparatus. The synthesis of glycoproteins is thus spatially separated in different cellular compartments, therefore, the type of N-glycan synthesised, depends on its accessibility to the different enzymes present within these cellular compartments. However, in spite of the diversity, all N-glycans are synthesised through a pathway with a common core glycan structure. The core glycan structure is made up of two N-acetyl glucosamine and three mannose residues. This core glycan is then elaborated and modified further, resulting in a range of N-glycan structures. The process of N-linked glycosylation starts with the formation of dolichol-linked GlcNAc sugar, dolichol is a lipid molecule composed of repeating isoprene units
. PMID 13630928. Retrieved 24 May 2014.
