1.
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
2.
GeneCards
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GeneCards is a database of human genes that provides genomic, proteomic, transcriptomic, genetic and functional information on all known and predicted human genes. It is being developed and maintained by the Crown Human Genome Center at the Weizmann Institute of Science and this database aims at providing a quick overview of the current available biomedical information about the searched gene, including the human genes, the encoded proteins, and the relevant diseases. The GeneCards database provides access to free Web resources about more than 7000 all known human genes that integrated from >90 data resources, such as HGNC, Ensembl, the core gene list is based on approved gene symbols published by the HUGO Gene Nomenclature Committee. The information are carefully gathered and selected from these databases by the powerful, over time, the GeneCards database has developed a suite of tools that has more specialised capability. Since 1998, the GeneCards database has been used by bioinformatics, genomics. Since the 1980s, sequence information has become abundant, many laboratories realized this. However, the information provided by the sequence databases focus on different aspect. To gather these scattered data, The Weizmann Institute of Science Crown Human Genome Centre developed a database called ‘GeneCards’ in 1997 and this database mainly deals with the human genome information, human genes, the encoded proteins’ functions, and the related diseases. At first, it includes two main features, the function to get integrated biomedical information about certain gene in ‘card’ format. Currently, the version 3 gather information from more than 90 database resources based on a consolidated gene list and it has developed a set of GeneCards suit, which are focus one more specific purposes. Nearly every 3 years life cycle, a new planning phase for subsequent revision will start, including implementation, development and semi-automated quality assurance, and deployment. Technologies used include Eclipse, Apache, Perl, XML, PHP, Propel, Java, R and MySQL. genecards. org/, annotation combinatory, Using GeneDecks, one can get a set of similar genes for a particular gene with a selected combinatorial annotation. The summary table result in ranking the different level of similarity between the genes and the probe gene. Annotation unification, Different data source often offer annotations with heterogeneous naming system, annotation unification of GeneDecks is based on the similarity in GeneCards gene-content space detection algorithms. Partner hunting, In GeneDecks’s Partner Hunter, users give a query gene, Set distillation, In Set distiller, users give a set of genes, and the system ranks attributes by their degree of sharing within a given gene set. GeneALaCart is a gene-set-orientated batch-querying engine based on the popular GeneCards database and it allows retrieval of information about multiple genes in a batch query. The GeneLoc suit member presents a human chromosome map, which is very important for designing a custom-made capture chip. GeneLoc includes further links to GeneCards, NCBIs Human Genome Sequencing, UniGene, firstly, enter what you want to search into the blank on the homepages
3.
Chromosome
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A chromosome is a DNA molecule with part or all of the genetic material of an organism. Prokaryotes usually have one single circular chromosome, whereas most eukaryotes are diploid, chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes, a nucleosome is a histone octamer with part of a longer DNA strand attached to and wrapped around it. Chromatin fiber, together with associated proteins is known as chromatin, chromatin is present in most cells, with a few exceptions, for example, red blood cells. Occurring only in the nucleus of cells, chromatin contains the vast majority of DNA, except for a small amount inherited maternally. Chromosomes are normally visible under a microscope only when the cell is undergoing the metaphase of cell division. Before this happens every chromosome is copied once, and the copy is joined to the original by a centromere resulting in an X-shaped structure, the original chromosome and the copy are now called sister chromatids. During metaphase, when a chromosome is in its most condensed state, in this highly condensed form chromosomes are easiest to distinguish and study. In prokaryotic cells, chromatin occurs free-floating in cytoplasm, as these cells lack organelles, the main information-carrying macromolecule is a single piece of coiled double-helix DNA, containing many genes, regulatory elements and other noncoding DNA. The DNA-bound macromolecules are proteins that serve to package the DNA, chromosomes vary widely between different organisms. Some species such as certain bacteria also contain plasmids or other extrachromosomal DNA and these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. Chromosomal recombination during meiosis and subsequent sexual reproduction plays a significant role in genetic diversity. In prokaryotes and viruses, the DNA is often densely packed and organized, in the case of archaea, by homologs to eukaryotic histones, small circular genomes called plasmids are often found in bacteria and also in mitochondria and chloroplasts, reflecting their bacterial origins. Some use the term chromosome in a sense, to refer to the individualized portions of chromatin in cells. However, others use the concept in a sense, to refer to the individualized portions of chromatin during cell division. The word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes, schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now so familiar to everyone as chromosomes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, in a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity. His two principles were the continuity of chromosomes and the individuality of chromosomes and it is the second of these principles that was so original
4.
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
5.
Base pair
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A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the blocks of the DNA double helix. Dictated by specific hydrogen bonding patterns, Watson-Crick base pairs allow the DNA helix to maintain a regular helical structure that is dependent on its nucleotide sequence. The complementary nature of this structure provides a backup copy of all genetic information encoded within double-stranded DNA. Many DNA-binding proteins can recognize specific base pairing patterns that identify particular regulatory regions of genes, intramolecular base pairs can occur within single-stranded nucleic acids. The size of a gene or an organisms entire genome is often measured in base pairs because DNA is usually double-stranded. Hence, the number of base pairs is equal to the number of nucleotides in one of the strands. The haploid human genome is estimated to be about 3.2 billion bases long and to contain 20, a kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the interaction that underlies the base-pairing rules described above. Appropriate geometrical correspondence of hydrogen donors and acceptors allows only the right pairs to form stably. Purine-pyrimidine base pairing of AT or GC or UA results in proper duplex structure, the only other purine-pyrimidine pairings would be AC and GT and UG, these pairings are mismatches because the patterns of hydrogen donors and acceptors do not correspond. The GU pairing, with two bonds, does occur fairly often in RNA. Higher GC content results in higher melting temperatures, it is, therefore, on the converse, regions of a genome that need to separate frequently — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must also be taken into account when designing primers for PCR reactions, the following DNA sequences illustrate pair double-stranded patterns. By convention, the top strand is written from the 5 end to the 3 end, thus and this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine, most intercalators are large polyaromatic compounds and are known or suspected carcinogens. Examples include ethidium bromide and acridine, an unnatural base pair is a designed subunit of DNA which is created in a laboratory and does not occur in nature
6.
Gene expression
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Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are proteins, but in non-protein coding genes such as transfer RNA or small nuclear RNA genes. The process of gene expression is used by all known life—eukaryotes, prokaryotes, several steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for differentiation, morphogenesis. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, the genetic code stored in DNA is interpreted by gene expression, and the properties of the expression give rise to the organisms phenotype. Such phenotypes are expressed by the synthesis of proteins that control the organisms shape. Regulation of gene expression is critical to an organisms development. A gene is a stretch of DNA that encodes information, genomic DNA consists of two antiparallel and reverse complementary strands, each having 5 and 3 ends. This RNA is complementary to the template 3 →5 DNA strand, therefore, the resulting 5 →3 RNA strand is identical to the coding DNA strand with the exception that thymines are replaced with uracils in the RNA. A coding DNA strand reading ATG is indirectly transcribed through the non-coding strand as AUG in RNA, in prokaryotes, transcription is carried out by a single type of RNA polymerase, which needs a DNA sequence called a Pribnow box as well as a sigma factor to start transcription. RNA polymerase I is responsible for transcription of ribosomal RNA genes, RNA polymerase II transcribes all protein-coding genes but also some non-coding RNAs. Pol II includes a C-terminal domain that is rich in serine residues, when these residues are phosphorylated, the CTD binds to various protein factors that promote transcript maturation and modification. RNA polymerase III transcribes 5S rRNA, transfer RNA genes, transcription ends when the polymerase encounters a sequence called the terminator. These include 5 capping, which is set of reactions that add 7-methylguanosine to the 5 end of pre-mRNA. The m7G cap is then bound by cap binding complex heterodimer, another modification is 3 cleavage and polyadenylation. They occur if polyadenylation signal sequence is present in pre-mRNA, which is usually between protein-coding sequence and terminator, the pre-mRNA is first cleaved and then a series of ~200 adenines are added to form poly tail, which protects the RNA from degradation. Poly tail is bound by multiple poly-binding proteins necessary for mRNA export, a very important modification of eukaryotic pre-mRNA is RNA splicing. The majority of eukaryotic pre-mRNAs consist of alternating segments called exons and introns, in certain cases, some introns or exons can be either removed or retained in mature mRNA
7.
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
8.
Ensembl genome database project
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Ensembl is one of several well known genome browsers for the retrieval of genomic information. Similar databases and browsers are found at NCBI and the University of California, the human genome consists of three billion base pairs, which code for approximately 20, 000–25,000 genes. However the genome alone is of use, unless the locations. One option is manual annotation, whereby a team of scientists tries to locate genes using experimental data from scientific journals, however this is a slow, painstaking task. The alternative, known as automated annotation, is to use the power of computers to do the complex pattern-matching of protein to DNA. In the Ensembl project, sequence data are fed into the gene annotation system which creates a set of predicted gene locations and saves them in a MySQL database for subsequent analysis, Ensembl makes these data freely accessible to the world research community. All the data and code produced by the Ensembl project is available to download, in addition, the Ensembl website provides computer-generated visual displays of much of the data. Over time the project has expanded to additional species as well as a wider range of genomic data, including genetic variations. Central to the Ensembl concept is the ability to automatically generate graphical views of the alignment of genes and these are shown as data tracks, and individual tracks can be turned on and off, allowing the user to customise the display to suit their research interests. The interface also enables the user to zoom in to a region or move along the genome in either direction, the graphics are complemented by tabular displays, and in many cases data can be exported directly from the page in a variety of standard file formats such as FASTA. Externally produced data can also be added to the display, either via a DAS server on the internet, or by uploading a file in one of the supported formats, such as BAM, BED. Graphics are generated using a suite of custom Perl modules based on GD, in addition to its website, Ensembl provides a Perl API that models biological objects such as genes and proteins, allowing simple scripts to be written to retrieve data of interest. The same API is used internally by the web interface to display the data and it is divided in sections like the core API, the compara API, the variation API, and the functional genomics API. The Ensembl website provides information on how to install and use the API. This software can be used to access the public MySQL database, the users could even choose to retrieve data from the MySQL with direct SQL queries, but this requires an extensive knowledge of the current database schema. Large datasets can be retrieved using the BioMart data-mining tool and it provides a web interface for downloading datasets using complex queries. Last, there is an FTP server which can be used to download entire MySQL databases as some selected data sets in other formats. The annotated genomes include most fully sequenced vertebrates and selected model organisms, all of them are eukaryotes, there are no prokaryotes
9.
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
10.
PubMed
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
11.
Wikidata
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Wikidata is a collaboratively edited knowledge base operated by the Wikimedia Foundation. It is intended to provide a source of data which can be used by Wikimedia projects such as Wikipedia. This is similar to the way Wikimedia Commons provides storage for files and access to those files for all Wikimedia projects. Wikidata is powered by the software Wikibase, Wikidata is a document-oriented database, focused on items. Each item represents a topic and is identified by a number, prefixed with the letter Q—for example. This enables the basic information required to identify the topic the item covers to be translated without favouring any language, information is added to items by creating statements. Statements take the form of pairs, with each statement consisting of a property. The creation of the project was funded by donations from the Allen Institute for Artificial Intelligence, the Gordon and Betty Moore Foundation, at this time, only the first phase was available. Historically, a Wikipedia article would include a list of links, being links to articles on the same topic in other editions of Wikipedia. Initially, Wikidata was a repository of interlanguage links. No Wikipedia language editions were able to access Wikidata, so they needed to continue to maintain their own lists of interlanguage links, on 14 January 2013, the Hungarian Wikipedia became the first to enable the provision of interlanguage links via Wikidata. This functionality was extended to the Hebrew and Italian Wikipedias on 30 January, to the English Wikipedia on 13 February, on 23 September 2013, phase 1 went live on Wikimedia Commons. The first aspects of the second phase were deployed on 4 February 2013, the values were initially limited to two data types, with more data types to follow later. The first new type, string, was deployed on 6 March, the ability of the various language editions of Wikipedia to access data added to Wikidata as part of phase two was rolled out progressively between 27 March and 25 April 2013. On 16 September 2015, Wikidata began allowing so-called arbitrary access, for example, in the past the article about Berlin you could not access data about Germany, but with arbitrary access it could. On 27 April 2016 arbitrary access was activated on Wikimedia Commons, phase 3 will involve database querying and the creation of lists based on data stored on Wikidata. As of October 2016 two tools for querying Wikidata were available, AutoList and PetScan, additionally to a public SPARQL endpoint, there is concern that the project is being influenced by lobbying companies, PR professionals and search engine optimizers. As of December 2015, according to Wikimedia statistics, half of the information in Wikidata is unsourced, another 30% is labeled as having come from Wikipedia, but with no indication as to which article
12.
BRENDA
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BRENDA is an information system representing one of the most comprehensive enzyme repositories. It is a resource that comprises molecular and biochemical information on enzymes that have been classified by the IUBMB. Every classified enzyme is characterized with respect to its catalyzed biochemical reaction, kinetic properties of the corresponding reactants are described in detail. BRENDA contains enzyme-specific data manually extracted from scientific literature and additional data derived from automatic information retrieval methods such as text mining. It provides a user interface that allows a convenient and sophisticated access to the data. BRENDA was founded in 1987 at the former German National Research Centre for Biotechnology in Braunschweig and was published as a series of books. Its name was originally an acronym for the Braunschweig Enzyme Database, from 1996 to 2007, BRENDA was located at the University of Cologne. There, BRENDA developed into a publicly accessible enzyme information system, in 2007, BRENDA returned to Braunschweig. Currently, BRENDA is maintained and further developed at the Department of Bioinformatics, a major update of the data in BRENDA is performed twice a year. Besides the upgrade of its content, improvements of the interface are also incorporated into the BRENDA database. The latest update was performed in January 2015, Database, The database contains more than 40 data fields with enzyme-specific information on more than 7000 EC numbers that are classified according to the IUBMB. Currently, BRENDA contains manually annotated data from over 140,000 different scientific articles, each enzyme entry is clearly linked to at least one literature reference, to its source organism, and, where available, to the protein sequence of the enzyme. An important part of BRENDA represent the more than 110,000 enzyme ligands, the term ligand is used in this context to all low molecular weight compounds which interact with enzymes. These include not only metabolites of primary metabolism, co-substrates or cofactors, the origin of these molecules ranges from naturally occurring antibiotics to synthetic compounds that have been synthesized for the development of drugs or pesticides. Furthermore, cross-references to external resources such as sequence and 3D-structure databases. Extensions, Since 2006, the data in BRENDA is supplemented with information extracted from the literature by a co-occurrence based text mining approach. For this purpose, four text-mining repositories FRENDA, AMENDA, DRENDA and KENDA were introduced and these text-mining results were derived from the titles and abstracts of all articles in the literature database PubMed. Data access, There are several tools to access to the data in BRENDA
13.
MetaCyc
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The MetaCyc database contains extensive information on metabolic pathways and enzymes from many organisms. MetaCyc is also used in engineering and metabolomics research. MetaCyc contains extensive data on individual enzymes, describing their subunit structure, cofactors, activators and inhibitors, substrate specificity, MetaCyc data on reactions includes predicted atom mappings that describe the correspondence between atoms in the reactant compounds and the product compounds. It also provides enzyme mini-reviews and literature references, MetaCyc data on metabolites includes chemical structures, predicted Gibbs free energies of formation, and links to external databases
14.
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
15.
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
16.
Phosphorylation
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Phosphorylation is the addition of a phosphoryl group − to a molecule. In biology, phosphorylation and its counterpart, dephosphorylation, are critical for cellular processes. A large fraction of proteins are at least temporarily phosphorylated, as are many sugars, lipids, Phosphorylation is especially important for protein function as this modification activates many enzymes, thereby regulating their function. Protein phosphorylation is one type of post-translational modification, the prominent role of protein phosphorylation in biochemistry is illustrated by the huge body of studies published on the subject. Phosphorylation of sugars is often the first stage of their catabolism and it allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism because many sugars are first converted to glucose before they are metabolized further. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by D-glucose + ATP -> D-glucose-6-phosphate + ADP ΔG° = -16.7 kJ/mol, the two enzymes have been identified as a specific glucokinase and non-specific hexokinase. Hepatic cell is freely permeable to glucose, and the rate of phosphorylation of glucose is the rate-limiting step in glucose metabolism by the liver. The role of glucose 6-phosphate in glycogen synthase, High blood glucose concentration causes an increase in levels of glucose 6 phosphate in liver, skeletal muscle. In liver, synthesis of glycogen is directly correlated by blood glucose concentration and in muscle and adipocytes. High blood glucose releases insulin, stimulating the trans location of specific glucose transporters to the cell membrane, the hexokinase enzyme has a low Km, indicating a high affinity for glucose, so this initial phosphorylation can proceed even when glucose levels at nanoscopic scale within the blood. The phosphorylation of glucose can be enhanced by the binding of Fructose-6-phosphate, fructose consumed in the diet is converted to F1P in the liver. This negates the action of F6P on glucokinase, which favors the forward reaction. The capacity of cells to phosphorylate fructose exceeds capacity of metabolize fructose-1-phosphate. Consuming excess fructose ultimately results in an imbalance in liver metabolism, Phosphorylation of glucose is imperative in processes within the body. For example, phosphorylating glucose is necessary for insulin-dependent mechanistic target of rapamycin pathway activity within the heart and this further suggests a link between intermediary metabolism and cardiac growth. Reversible phosphorylation of proteins is an important regulatory mechanism occurs in both prokaryotic and eukaryotic organisms. Kinases phosphorylate proteins and phosphatases dephosphorylate proteins, many enzymes and receptors are switched on or off by phosphorylation and dephosphorylation
17.
Cell (biology)
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The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life that can replicate independently, the study of cells is called cell biology. Cells consist of cytoplasm enclosed within a membrane, which contains many such as proteins. Organisms can be classified as unicellular or multicellular, while the number of cells in plants and animals varies from species to species, humans contain more than 10 trillion cells. Most plant and animal cells are only under a microscope. The cell was discovered by Robert Hooke in 1665, who named the unit for its resemblance to cells inhabited by Christian monks in a monastery. Cells emerged on Earth at least 3.5 billion years ago, Cells are of two types, eukaryotic, which contain a nucleus, and prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular, prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling and being self-sustaining. They are simpler and smaller than eukaryotic cells, and lack membrane-bound organelles such as the nucleus, prokaryotes include two of the domains of life, bacteria and archaea. The DNA of a prokaryotic cell consists of a chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid, most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. Though most prokaryotes have both a cell membrane and a wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, the cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment, some eukaryotic cells also have a cell wall. Inside the cell is the region that contains the genome, ribosomes. The genetic material is found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular, linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid, plasmids encode additional genes, such as antibiotic resistance genes
18.
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
19.
Carbohydrate
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A carbohydrate is a biological molecule consisting of carbon, hydrogen and oxygen atoms, usually with a hydrogen–oxygen atom ratio of 2,1, in other words, with the empirical formula Cmn. This formula holds true for monosaccharides, some exceptions exist, for example, deoxyribose, a sugar component of DNA, has the empirical formula C5H10O4. Carbohydrates are technically hydrates of carbon, structurally it is accurate to view them as polyhydroxy aldehydes and ketones. The term is most common in biochemistry, where it is a synonym of saccharide, a group that includes sugars, starch, the saccharides are divided into four chemical groups, monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Monosaccharides and disaccharides, the smallest carbohydrates, are referred to as sugars. The word saccharide comes from the Greek word σάκχαρον, meaning sugar, while the scientific nomenclature of carbohydrates is complex, the names of the monosaccharides and disaccharides very often end in the suffix -ose. For example, grape sugar is the glucose, cane sugar is the disaccharide sucrose. Carbohydrates perform numerous roles in living organisms, polysaccharides serve for the storage of energy and as structural components. The 5-carbon monosaccharide ribose is an important component of coenzymes and the backbone of the genetic molecule known as RNA, the related deoxyribose is a component of DNA. Saccharides and their derivatives include many other important biomolecules that play key roles in the system, fertilization, preventing pathogenesis, blood clotting. In food science and in informal contexts, the term carbohydrate often means any food that is particularly rich in the complex carbohydrate starch or simple carbohydrates. Often in lists of information, such as the USDA National Nutrient Database, the term carbohydrate is used for everything other than water, protein, fat, ash. This will include chemical compounds such as acetic or lactic acid, carbohydrates are found in wide variety of foods. The important sources are cereals, potatoes, sugarcane, fruits, table sugar, bread, milk, starch and sugar are the important carbohydrates in our diet. Starch is abundant in potatoes, maize, rice and other cereals, sugar appears in our diet mainly as sucrose which is added to drinks and many prepared foods such as jam, biscuits and cakes. Glucose and fructose are found naturally in fruits and some vegetables. Glycogen is carbohydrate found in the liver and muscles, cellulose in the cell wall of all plant tissue is a carbohydrate. It is important in our diet as fibre which helps to maintain a healthy digestive system, formerly the name carbohydrate was used in chemistry for any compound with the formula Cm n
20.
Metabolism
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Metabolism is the set of life-sustaining chemical transformations within the cells of living organisms. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, usually, breaking down releases energy and building up consumes energy. The chemical reactions of metabolism are organized into metabolic pathways, in one chemical is transformed through a series of steps into another chemical. Enzymes act as catalysts that allow the reactions to proceed more rapidly, enzymes also allow the regulation of metabolic pathways in response to changes in the cells environment or to signals from other cells. The metabolic system of a particular organism determines which substances it will find nutritious, for example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The speed of metabolism, the rate, influences how much food an organism will require. A striking feature of metabolism is the similarity of the metabolic pathways. These striking similarities in metabolic pathways are likely due to their appearance in evolutionary history. Most of the structures that make up animals, plants and microbes are made from three classes of molecule, amino acids, carbohydrates and lipids. These biochemicals can be joined together to make such as DNA and proteins. Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds, many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle. Lipids are the most diverse group of biochemicals and their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy. Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform, the fats are a large group of compounds that contain fatty acids and glycerol, a glycerol molecule attached to three fatty acid esters is called a triacylglyceride. Several variations on this structure exist, including alternate backbones such as sphingosine in the sphingolipids. Steroids such as cholesterol are another class of lipids. Carbohydrates are aldehydes or ketones, with hydroxyl groups attached. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy, the basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose
21.
Sensor
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A sensor is always used with other electronics, whether as simple as a light or as complex as a computer. Moreover, analog sensors such as potentiometers and force-sensing resistors are still widely used, applications include manufacturing and machinery, airplanes and aerospace, cars, medicine, robotics and many other aspects of our day-to-day life. A sensors sensitivity indicates how much the output changes when the input quantity being measured changes. For instance, if the mercury in a thermometer moves 1 cm when the changes by 1 °C. Some sensors can also affect what they measure, for instance, Sensors are usually designed to have a small effect on what is measured, making the sensor smaller often improves this and may introduce other advantages. Technological progress allows more and more sensors to be manufactured on a scale as microsensors using MEMS technology. In most cases, a microsensor reaches a higher speed. Most sensors have a transfer function. The sensitivity is defined as the ratio between the output signal and measured property. For example, if a sensor measures temperature and has a voltage output, the sensitivity is the slope of the transfer function. Converting the sensors electrical output to the measured units requires dividing the output by the slope. In addition, an offset is added or subtracted. For example -40 must be added to the output if 0 V output corresponds to -40 C input, for an analog sensor signal to be processed, or used in digital equipment, it needs to be converted to a digital signal, using an analog-to-digital converter. The full scale range defines the maximum and minimum values of the measured property, the sensitivity may in practice differ from the value specified. This is called a sensitivity error and this is an error in the slope of a linear transfer function. If the output differs from the correct value by a constant. This is an error in the y-intercept of a transfer function. Nonlinearity is deviation of a transfer function from a straight line transfer function
22.
Fasting
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Fasting is a willing abstinence or reduction from some or all food, drink, or both, for a period of time. An absolute fast is normally defined as abstinence from all food and liquid for a period, usually a period of 24 hours. Water fasting allows drinking water but nothing else, other fasts may be partially restrictive, limiting only particular foods or substances. A fast may also be intermittent in nature, Fasting practices may preclude intercourse and other activities as well as food. In a physiological context, fasting may refer to the status of a person who has not eaten overnight. Several metabolic adjustments occur during fasting, and some tests are used to determine a fasting state. For example, a person is assumed to be fasting after 8–12 hours from their last meal, metabolic changes toward the fasting state begin after absorption of a meal, post-absorptive state is synonymous with this usage, in contrast to the postprandial state of ongoing digestion. A diagnostic fast refers to prolonged fasting conducted under observation for investigation of a problem, many people may also fast as part of a medical procedure or check-up such as a colonoscopy. Fasting is also a part of religious observances. Fasting is often practiced prior to surgery or other procedures that require general anesthetics because of the risk of aspiration of gastric contents after induction of anesthesia. Additionally, certain tests, such as cholesterol testing or certain blood glucose measurements require fasting for several hours so that a baseline can be established. In the case of a panel, failure to fast for a full 12 hours will guarantee an elevated triglyceride measurement. Fasting is of no help in preventing or treating cancer. Fasting can help alleviate symptoms of depression. However the psychological effects may include anxiety and depression. Fasting will lead to weight loss, using fasting for weight loss is considered dangerous. It has been argued that fasting makes one better appreciate food, Fasting is often used as a tool to make a political statement, to protest, or to bring awareness to a cause. A hunger strike is a method of non-violent resistance in which participants fast as an act of political protest, or to provoke feelings of guilt, a spiritual fast incorporates personal spiritual beliefs with the desire to express personal principles, sometimes in the context of a social injustice
23.
Mutagen
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In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer, mutagens are also likely to be carcinogens. Some chemicals only become mutagenic through cellular processes, not all mutations are caused by mutagens, so-called spontaneous mutations occur due to spontaneous hydrolysis, errors in DNA replication, repair and recombination. The first mutagens to be identified were carcinogens, substances that were shown to be linked to cancer. Tumors were described more than 2,000 years before the discovery of chromosomes and DNA, in 500 B. C. the Greek physician Hippocrates named tumors resembling a crab karkinos, meaning crab. In 1775, Sir Percivall Pott wrote a paper on the incidence of scrotal cancer in chimney sweeps. In 1915, Yamagawa and Ichikawa showed that repeated application of coal tar to rabbits ears produced malignant cancer, subsequently, in the 1930s the carcinogen component in coal tar was identified as a polyaromatic hydrocarbon, benzopyrene. Polyaromatic hydrocarbons are also present in soot, which was suggested to be an agent of cancer over 150 years earlier. His collaborator Edgar Altenburg also demonstrated the effect of UV radiation in 1928. Muller went on to use x-rays to create Drosophila mutants that he used in his studies of genetics and he also found that X-rays not only mutate genes in fruit flies but also have effects on the genetic makeup of humans. Similar work by Lewis Stadler also showed the effect of X-ray on barley in 1928. The effect of sunlight had previously noted in the nineteenth century where rural outdoor workers and sailors were found to be more prone to skin cancer. Chemical mutagens were not demonstrated to cause mutation until the 1940s, early studies by Ames showed around 90% of known carcinogens can be identified in Ames test as mutagenic, and ~80% of the mutagens identified through Ames test may also be carcinogens. Mutagens are not necessarily carcinogens, and vice versa, sodium azide for example may be mutagenic, but it has not been shown to be carcinogenic. Mutagens can cause changes to the DNA and are therefore genotoxic and they can affect the transcription and replication of the DNA, which in severe cases can lead to cell death. The mutagen produces mutations in the DNA, and deleterious mutation can result in aberrant, impaired or loss of function for a particular gene, mutagens may therefore be also carcinogens. Different mutagens act on the DNA differently, powerful mutagens may result in chromosomal instability, causing chromosomal breakages and rearrangement of the chromosomes such as translocation, deletion, and inversion. Some mutagens can cause aneuploidy and change the number of chromosomes in the cell, in Ames test, where the varying concentrations of the chemical are used in the test, the dose response curve obtained is nearly always linear, suggesting that there is no threshold for mutagenesis
24.
Gene
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A gene is a locus of DNA which is made up of nucleotides and is the molecular unit of heredity. The transmission of genes to an offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes, genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions, genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits, usage of the term having a gene typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection or survival of the fittest of the alleles, the concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. The existence of discrete inheritable units was first suggested by Gregor Mendel, from 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas, although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype and phenotype, charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction, de Vries called these units pangenes, after Darwins 1868 pangenesis theory. In 1909 the Danish botanist Wilhelm Johannsen shortened the name to gene, advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the repository of genetic information by experiments in the 1940s to 1950s. In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination, collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics, in 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene, the gene for Bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing, an automated version of the Sanger method was used in early phases of the Human Genome Project. The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the evolutionary synthesis
25.
Hexokinase
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A hexokinase is an enzyme that phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate of hexokinases, scientists have discovered and demonstrated that Hexokinase posses the ability to transfer a inorganic phosphate group from ATP to a substrate. Hexokinases should not be confused with glucokinase, which is an isoform of hexokinase. While other hexokinases are capable of phosphorylating several hexoses, glucokinase acts with a 50-fold lower substrate affinity and its only hexose substrate is glucose. Genes that encode hexokinase have been discovered in every domain of life, and exist among a variety of species range from bacteria, yeast. They are categorized as actin fold proteins, sharing a common ATP binding site core that is surrounded by more variable sequences which determine substrate affinities, several hexokinase isoforms or isozymes that provide different functions can occur in a single species. Phosphorylation of a such as glucose often limits it to a number of intracellular metabolic processes. This is because phosphorylated hexoses are charged, and thus difficult to transport out of a cell. Most bacterial hexokinases are approximately 50 kD in size, multicellular organisms including plants and animals often have more than one hexokinase isoform. Most are about 100 kD in size and consist of two halves, which share much sequence homology and this suggests an evolutionary origin by duplication and fusion of a 50kD ancestral hexokinase similar to those of bacteria. There are four important mammalian hexokinase isozymes that vary in subcellular locations and kinetics with respect to different substrates and conditions, and physiological function. They are designated hexokinases I, II, III, and IV or hexokinases A, B, C, and D. Hexokinases I, II, Hexokinases I and II follow Michaelis-Menten kinetics at physiologic concentrations of substrates. All three are strongly inhibited by their product, glucose-6-phosphate, molecular weights are around 100 kD. Each consists of two similar 50kD halves, but only in hexokinase II do both halves have functional active sites, Hexokinase I/A is found in all mammalian tissues, and is considered a housekeeping enzyme, unaffected by most physiological, hormonal, and metabolic changes. Hexokinase II/B constitutes the principal regulated isoform in many types and is increased in many cancers. It is the hexokinase found in muscle and heart, Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP. Hexokinase III/C is substrate-inhibited by glucose at physiologic concentrations, little is known about the regulatory characteristics of this isoform. Mammalian hexokinase IV, also referred to as glucokinase, differs from other hexokinases in kinetics, the location of the phosphorylation on a subcellular level occurs when glucokinase translocates between the cytoplasm and nucleus of liver cells
26.
Isozyme
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Isozymes are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters, or different regulatory properties, the existence of isozymes permits the fine-tuning of metabolism to meet the particular needs of a given tissue or developmental stage. In biochemistry, isozymes are isoforms of enzymes, in many cases, they are coded for by homologous genes that have diverged over time. Isozymes were first described by R. L, hunter and Clement Markert who defined them as different variants of the same enzyme having identical functions and present in the same individual. This definition encompasses enzyme variants that are the product of different genes and thus represent different loci, isozymes are usually the result of gene duplication, but can also arise from polyploidisation or nucleic acid hybridization. Over evolutionary time, if the function of the new variant remains identical to the original, then it is likely one or the other will be lost as mutation accumulate. For example, they may be expressed at different stages of development or in different tissues, allozymes may result from point mutations or from insertion-deletion events that affect the DNA coding sequence of the gene. Alternatively, if the acid residue that is changed is in a relatively unimportant part of the enzyme, then the mutation may be selectively neutral. An example of an isozyme is glucokinase, a variant of hexokinase which is not inhibited by glucose 6-phosphate, both of these processes must only occur when glucose is abundant, or problems occur. Unless they are identical in terms of their properties, for example their substrates and enzyme kinetics. However, such differences are usually subtle and this subtlety is to be expected, because two enzymes that differ significantly in their function are unlikely to have been identified as isozymes. Whilst isozymes may be almost identical in function, they may differ in other ways, historically, this has usually been done using gels made from potato starch, but acrylamide gels provide better resolution. All the proteins from the tissue are present in the gel and this assay method requires that the enzymes are still functional after separation, and provides the greatest challenge to using isozymes as a laboratory technique. The cytochrome P450 isozymes play important roles in metabolism and steroidogenesis, the multiple forms of phosphodiesterase also play major roles in various biological processes. Although more than one form of enzymes have been found in individual cells. From the clinical standpoint they have found to be selectively activated and inhibited. Histochemical demonstration of enzymes separated by electrophoresis in starch gels. Science 125, 1294-1295 Weiss, B. and Hait, W. N, selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents
27.
Homology (biology)
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In biology, homology is the existence of shared ancestry between a pair of structures, or genes, in different taxa. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor, examples include the legs of a centipede, the maxillary palp and labial palp of an insect, and the spinous processes of successive vertebrae in a vertebral column. Sequence homology between protein or DNA sequences is defined in terms of shared ancestry. Two segments of DNA can have shared ancestry because of either an event or a duplication event. Homology among proteins or DNA is inferred from their sequence similarity, significant similarity is strong evidence that two sequences are related by divergent evolution from a common ancestor. Alignments of multiple sequences are used to discover the homologous regions, the word homology, coined in about 1656, derives from the Greek ὁμόλογος homologos from ὁμός homos same and λόγος logos relation. Homology is the relationship between biological structures or sequences that are derived from a common ancestor, for example, many insects possess two pairs of flying wings. In beetles, the first pair of wings has evolved into a pair of hard wing covers, the same major forearm bones are found in fossils of lobe-finned fish such as Eusthenopteron. The opposite of homologous organs are analogous organs which do similar jobs in two taxa that were not present in their last common ancestor but rather evolved separately. For example, the wings of insects and birds evolved independently in widely separated groups, similarly, the wings of a sycamore maple seed and the wings of a bird are analogous but not homologous, as they develop from quite different structures. A structure can be homologous at one level, but only analogous at another, for example, in the pterosaurs, the wing involves both the forelimb and the hindlimb. Analogy is called homoplasy in cladistics, and convergent or parallel evolution in evolutionary biology, specialised terms are used in taxonomic research. Primary homology is that initially conjectured by a researcher based on similar structure or anatomical connections, secondary homology is implied by parsimony analysis, where a character that only occurs once on a tree is taken to be homologous. As implied in this definition, many cladists consider homology to be synonymous with synapomorphy, homologies provide the fundamental basis for all biological classification, although some may be highly counter-intuitive. The homologies between these have been discovered by comparing genes in evolutionary developmental biology, among insects, the stinger of the female honey bee is a modified ovipositor, homologous with ovipositors in other insects such as the Orthoptera, Hemiptera, and those Hymenoptera without stingers. The three small bones in the ear of mammals including humans, the malleus, incus. The malleus and incus develop in the embryo from structures that form jaw bones in lizards, both lines of evidence show that these bones are homologous, sharing a common ancestor. Among the many homologies in mammal reproductive systems, ovaries and testicles are homologous, in many plants, defensive or storage structures are made by modifications of the development of primary leaves, stems, and roots
28.
Glycogen
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Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in humans, animals, and fungi. The polysaccharide structure represents the main form of glucose in the body. In humans, glycogen is made and stored primarily in the cells of the liver, glycogen functions as the secondary long-term energy storage, with the primary energy stores being fats held in adipose tissue. Muscle glycogen is converted into glucose by muscle cells, and liver glycogen converts to glucose for use throughout the body including the nervous system. Glycogen is the analogue of starch, a polymer that functions as energy storage in plants. It has a similar to amylopectin, but is more extensively branched. Both are white powders in their dry state, glycogen is found in the form of granules in the cytosol/cytoplasm in many cell types, and plays an important role in the glucose cycle. Glycogen forms a reserve that can be quickly mobilized to meet a sudden need for glucose. In the liver, glycogen can make up from 5–6% of the fresh weight. Only the glycogen stored in the liver can be accessible to other organs. In the muscles, glycogen is found in a low concentration, the amount of glycogen stored in the body—especially within the muscles, liver, and red blood cells—mostly depends on physical training, basal metabolic rate, and eating habits. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain cells in the brain. The uterus also stores glycogen during pregnancy to nourish the embryo, glycogen is a branched biopolymer consisting of linear chains of glucose residues with further chains branching off every 8 to 12 glucoses or so. Glucoses are linked together linearly by α glycosidic bonds from one glucose to the next, branches are linked to the chains from which they are branching off by α glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain. Due to the way glycogen is synthesised, every glycogen granule has at its core a glycogenin protein. Glycogen in muscle, liver, and fat cells is stored in a hydrated form, as a meal containing carbohydrates or protein is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Blood glucose from the vein enters liver cells. Insulin acts on the hepatocytes to stimulate the action of several enzymes, glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful
29.
Glycolysis
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Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP, glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis, for example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful, for example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it not use molecular oxygen for any of its reactions. However the products of glycolysis are sometimes metabolized using atmospheric oxygen, when molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic. Thus, glycolysis occurs, with variations, in all organisms. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways, glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the cytosol of the cell, the most common type of glycolysis is the Embden–Meyerhof–Parnas, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway, however, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The overall reaction of glycolysis is, The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. In the cellular environment, all three groups of ADP dissociate into −O− and H+, giving ADP3−, and this ion tends to exist in an ionic bond with Mg2+. ATP behaves identically except that it has four groups, giving ATPMg2−. When these differences along with the charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP, most cells will then carry out further reactions to repay the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+, cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis. These further aerobic reactions use pyruvate and NADH + H+ from glycolysis, the pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many experiments were required in order to understand the pathway as a whole
30.
Genetic code
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The genetic code is the set of rules by which information encoded within genetic material is translated into proteins by living cells. Translation is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA molecules to carry amino acids, the genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries. The code defines how sequences of nucleotide triplets, called codons, with some exceptions, a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of genes are encoded with a single scheme and that scheme is often referred to as the canonical or standard genetic code, or simply the genetic code, though variant codes exist. While the genetic code determines a proteins amino acid sequence, other genomic regions determine when, efforts to understand how proteins are encoded began after DNAs structure was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins, the Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases. Marshall Nirenberg and Heinrich J. Matthaei were the first to reveal the nature of a codon in 1961 and they used a cell-free system to translate a poly-uracil RNA sequence and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced that the codon UUU specified the amino acid phenylalanine, therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using various copolymers most of the remaining codons were then determined, subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA and this work was based upon Ochoas earlier studies, yielding the latter the Nobel Prize in Physiology or Medicine in 1959 for work on the enzymology of RNA synthesis. Extending this work, Nirenberg and Philip Leder revealed the triplet nature. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments, Khorana, Holley and Nirenberg received the 1968 Nobel for their work. The three stop codons were named by discoverers Richard Epstein and Charles Steinberg, amber was named after their friend Harris Bernstein, whose last name means amber in German. The other two stop codons were named ochre and opal in order to keep the color names theme, H. Murakami and M. Sisido extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th codon, in 2016 the first stable semisynthetic organism was created. It was a bacterium with two synthetic bases, in 2017 a mouse engineered with an extended genetic code that can produce proteins with unnatural amino acids was reported. A codon is defined by the initial nucleotide from which starts and sets the frame for a run of successive triplets
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Enzyme kinetics
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Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the rate is measured and the effects of varying the conditions of the reaction are investigated. Enzymes are usually protein molecules that manipulate other molecules — the enzymes substrates, kinetic studies on enzymes that only bind one substrate, such as triosephosphate isomerase, aim to measure the affinity with which the enzyme binds this substrate and the turnover rate. Some other examples of enzymes are phosphofructokinase and hexokinase, both of which are important for cellular respiration, when enzymes bind multiple substrates, such as dihydrofolate reductase, enzyme kinetics can also show the sequence in which these substrates bind and the sequence in which products are released. An example of enzymes that bind a single substrate and release multiple products are proteases, others join two substrates together, such as DNA polymerase linking a nucleotide to DNA. Although these mechanisms are often a series of steps, there is typically one rate-determining step that determines the overall kinetics. This rate-determining step may be a reaction or a conformational change of the enzyme or substrates. Knowledge of the structure is helpful in interpreting kinetic data. For example, the structure can suggest how substrates and products bind during catalysis, what changes occur during the reaction, not all biological catalysts are protein enzymes, RNA-based catalysts such as ribozymes and ribosomes are essential to many cellular functions, such as RNA splicing and translation. The main difference between ribozymes and enzymes is that RNA catalysts are composed of nucleotides, whereas enzymes are composed of amino acids, ribozymes also perform a more limited set of reactions, although their reaction mechanisms and kinetics can be analysed and classified by the same methods. The reaction catalysed by an enzyme uses exactly the same reactants, like other catalysts, enzymes do not alter the position of equilibrium between substrates and products. However, unlike uncatalysed chemical reactions, enzyme-catalysed reactions display saturation kinetics, the substrate concentration midway between these two limiting cases is denoted by KM. The two most important kinetic properties of an enzyme are how quickly the enzyme becomes saturated with a substrate. Knowing these properties suggests what an enzyme might do in the cell, Enzyme assays are laboratory procedures that measure the rate of enzyme reactions. Because enzymes are not consumed by the reactions they catalyse, enzyme assays usually follow changes in the concentration of substrates or products to measure the rate of reaction. There are many methods of measurement, spectrophotometric assays are most convenient since they allow the rate of the reaction to be measured continuously. Although radiometric assays require the removal and counting of samples they are extremely sensitive. An analogous approach is to use mass spectrometry to monitor the incorporation or release of stable isotopes as substrate is converted into product, the most sensitive enzyme assays use lasers focused through a microscope to observe changes in single enzyme molecules as they catalyse their reactions
. PMID 18726182.
