1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
Chromosome 7 (human)
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Chromosome 7 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, chromosome 7 spans about 159 million base pairs and represents between 5 and 5.5 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 10%, with one estimate giving 2,774 genes, and the other estimate giving 2,500 genes. The deleted region, which is located at position 11.23, is designated as the Williams syndrome critical region. This region includes more than 20 genes, and researchers believe that the features of Williams syndrome are probably related to the loss of multiple genes in this region. These changes include a copy of part of chromosome 7 in each cell or a missing segment of the chromosome in each cell. In some cases, several DNA building blocks are deleted or duplicated in part of chromosome 7, a circular structure called ring chromosome 7 is also possible. A ring chromosome occurs when both ends of a chromosome are reunited. Chromosome 7 - NCBI Map Viewer
9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
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
17.
HUGO Gene Nomenclature Committee
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The HUGO Gene Nomenclature Committee is a committee of the Human Genome Organisation that sets the standards for human gene nomenclature. The HGNC approves a unique and meaningful name for every known human gene, in addition to the name, which is usually 1 to 10 words long, the HGNC also assigns a symbol to every gene. As with an SI symbol, a symbol is like an abbreviation but is more than that. It may not necessarily stand for the initials of the name, especially gene abbreviations/symbols but also full gene names are often not specific for a single gene. A marked example is CAP which can refer to any of 6 different genes, the HGNC short gene names, or gene symbols, unlike previously used or published symbols, are specifically assigned to one gene only. This can result in less common abbreviations being selected but reduces confusion as to which gene is referred to. e, h/h for human The full description of HGNCs nomenclature guidelines can be found on their web site. HGNC advocates the appendices _v1, _v2. to distinguish between different splice variants and _pr1, _pr2. for promoter variants of a single gene. HGNC also states that gene nomenclature should evolve with new technology rather than be restrictive as sometimes occurs when historical, HGNC also coordinates with the related Mouse and Rat Genomic Nomenclature Committees, other database curators, and experts for given specific gene families or sets of genes. For this reason the HGNC aims to change a name only if agreement for that change can be reached among a majority of researchers working on that gene. Human Genome Organisation Human Genome Project Human genome Gene Gene nomenclature HGNC homepage HUGO homepage
18.
Cholinesterase
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In biochemistry, a cholinesterase or choline esterase is an esterase that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and these reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. The main type for that purpose is acetylcholinesterase, it is mainly in chemical synapses. The other type is butyrylcholinesterase, it is mainly in the blood plasma. The two types of cholinesterase are acetylcholinesterase and butyrylcholinesterase, the difference between the two types has to do with their respective preferences for substrates, the former hydrolyses acetylcholine more quickly, the latter hydrolyses butyrylcholine more quickly. But such usage is now outdated, the current, unambiguous HGNC names, acetylcholinesterase exists in multiple molecular forms. In the mammalian brain the majority of AChE occurs as a tetrameric, the butyl and butyryl syllables both refer to butane with one of its terminal methyl groups substituted. The half-life of BCHE is approximately 10 to 14 days, BCHE levels may be reduced in patients with advanced liver disease. The decrease must be greater than 75% before significant prolongation of neuromuscular blockade occurs with succinylcholine, in 1968, Walo Leuzinger et al. successfully purified and crystallized acetylcholinesterase from electric eels at Columbia University, NY. The 3D structure of acetylcholinesterase was first determined in 1991 by Joel Sussman et al. using protein from the Pacific electric ray, clinically useful quantities of butyrylcholinesterase were synthesized in 2007 by PharmAthene, through the use of genetically modified goats. An absence or mutation of the BCHE enzyme leads to a condition known as pseudocholinesterase deficiency. This is a silent condition that manifests itself only when people that have the deficiency receive the muscle relaxants succinylcholine or mivacurium during a surgery, pseudocholinesterase deficiency may also affect local anaesthetic selection in dental procedures. The selection of a solution is recommended in such patients. Elevation of plasma BCHE levels was observed in 90. 5% cases of myocardial infarction. The presence of ACHE in the fluid may be tested in early pregnancy. A sample of fluid is removed by amniocentesis, and presence of ACHE can confirm several common types of birth defect, including abdominal wall defects. BCHE can be used as an agent against nerve gas. A cholinesterase inhibitor suppresses the action of the enzyme, the enzyme acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax
19.
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
20.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
21.
Acetylcholine
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Its name is derived from its chemical structure, it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic, substances that interfere with acetylcholine activity are called anticholinergics. Acetylcholine is the used at the neuromuscular junction—in other words. This property means that drugs that affect cholinergic systems can have dangerous effects ranging from paralysis to convulsions. In the brain, acetylcholine functions as a neurotransmitter and as a neuromodulator, the brain contains a number of cholinergic areas, each with distinct functions. They play an important role in arousal, attention, memory, scopolamine, which acts mainly on muscarinic receptors in the brain, can cause delirium and amnesia. The addictive qualities of nicotine derive from its effects on nicotinic receptors in the brain. Acetylcholine has functions both in the nervous system and in the central nervous system. In the peripheral nervous system, acetylcholine activates muscles, and is a major neurotransmitter in the nervous system. In the CNS, cholinergic projections from the basal forebrain to the cerebral cortex, like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two classes of acetylcholine receptor, nicotinic and muscarinic. Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium, potassium, in other words, they are ion channels embedded in cell membranes, capable of switching from a closed to open state when acetylcholine binds to them, in the open state they allow ions to pass through. Nicotinic receptors come in two types, known as muscle-type and neuronal-type. The muscle-type can be blocked by curare, the neuronal-type by hexamethonium. The main location of muscle-type receptors is on muscle cells, as described in detail below. Neuronal-type receptors are located in autonomic ganglia, and in the nervous system. Muscarinic acetylcholine receptors have a complex mechanism, and affect target cells over a longer time frame. In mammals, five subtypes of muscarinic receptors have been identified, labeled M1 through M5, all of them function as G protein-coupled receptors, meaning that they exert their effects via a second messenger system
22.
Choline
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Choline is a water-soluble vitamin-like essential nutrient. The term cholines refers to the class of quaternary ammonium salts containing the N, N, the cation appears in the head groups of phosphatidylcholine and sphingomyelin, two classes of phospholipid that are abundant in cell membranes. Choline is the molecule for the neurotransmitter acetylcholine, which is involved in many functions including memory. Some animals cannot produce choline, but must consume it through their diet to remain healthy, humans make choline in the liver. Whether dietary or supplemental choline is beneficial or harmful to humans is undefined, possible dangers include increased risk of cardiovascular disease and cancer, while possible benefits include reducing the risk of neural tube defects and fatty liver disease. According to the US Institute of Medicine, there is not enough evidence to establish a Recommended Daily Intake for choline. The Australian and New Zealand national nutrition bodies note that while deficiency has been seen during experiments, all three have published an Adequate Intake value, discussed below. The European Unions food safety authority says there are no Recommended Daily Intakes in the EU, methionine and folate are known to interact with choline while homocysteine is undergoing methylation to produce methionine. Recent studies have shown that choline deficiency may have effects, even when sufficient amounts of methionine. Choline was first isolated by Adolph Strecker from pig and ox bile in 1862, when it was first chemically synthesized by Oscar Liebreich in 1865, it was known as neurine until 1898 when it was shown to be chemically identical to choline. In 1998, choline was classified as an essential nutrient by the Food, Choline is a quaternary ammonium salt with the chemical formula 3N+2OHX−, where X− is a counterion such as chloride, hydroxide or tartrate. Choline chloride can form a deep eutectic solvent mixture with urea with unusual properties. The salicylate salt is used topically for pain relief of aphthous ulcers, Choline hydroxide is one of the class of phase transfer catalysts that are used to carry the hydroxide ion into organic systems, and, therefore, is considered a strong base. It is the phase transfer catalyst, and is used as an effective method of stripping photoresists in circuit boards. Choline hydroxide is not completely stable, and it breaks down into trimethylamine. Choline is a precursor to trimethylamine, which some persons are not able to break due to a genetic disorder called trimethylaminuria. Persons suffering from this disorder may suffer from a strong fishy or otherwise unpleasant body odor, a body odor will occur even on a normal diet – i. e. one that is not particularly high in choline. Persons with trimethylaminuria are advised to restrict the intake of foods high in choline, the following are choline values for a selection of foods in quantities that people may consume in a day
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Neurotransmitter
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Neurotransmitters, also known as chemical messengers, are endogenous chemicals that enable neurotransmission. They transmit signals across a synapse, such as a neuromuscular junction, from one neuron to another target neuron, muscle cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 100 chemical messengers have been uniquely identified, neurotransmitters are stored in a synapse in synaptic vesicles, clustered beneath the membrane in the axon terminal located at the presynaptic side of the synapse. Neurotransmitters are released into and diffused across the cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse. Most neurotransmitters are about the size of an amino acid, however. Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission, in response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level baseline release also occurs without electrical stimulation, the released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way and this neuron may be connected to many more neurons, and if the total of excitatory influences are greater than those of inhibitory influences, the neuron will also fire. Ultimately it will create a new action potential at its axon hillock to release neurotransmitters, until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter, some neurons do, however, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four criteria for identifying neurotransmitters, The chemical must be synthesized in the neuron or otherwise be present in it. When the neuron is active, the chemical must be released, the same response must be obtained when the chemical is experimentally placed on the target. A mechanism must exist for removing the chemical from its site of activation after its work is done, have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending messages that affect the release or reuptake of transmitters. Various techniques and experiments such as staining, stimulating, and collecting can be used to identify throughout the central nervous system. There are many different ways to classify neurotransmitters, dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes
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Neuromuscular junction
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A neuromuscular junction is a chemical synapse formed by the contact between a motor neuron and a muscle fiber. It is at the junction that a motor neuron is able to transmit a signal to the muscle fiber. Muscles require innervation to function—and even just to muscle tone. Calcium ions bind to sensor proteins on synaptic vesicles, triggering vesicle fusion with the cell membrane, nAChRs are ionotropic receptors, meaning they serve as ligand-gated ion channels. The binding of ACh to the receptor can depolarize the muscle fiber, neuromuscular junction diseases can be of genetic and autoimmune origin. The neuromuscular junction differs from chemical synapses between neurons, presynaptic motor axons stop 30 nanometers from the sarcolemma, the cell membrane of a muscle cell. This 30-nanometer space forms the synaptic cleft through which signalling molecules are released, the sarcolemma has invaginations called postjunctional folds, which increase the surface area of the membrane exposed to the synaptic cleft. These postjunctional folds form what is referred to as the motor endplate, the presynaptic axons form bulges called terminal boutons that project into the postjunctional folds of the sarcolemma. The presynaptic terminals have active zones that contain vesicles, also called quanta and these vesicles can fuse with the presynaptic membrane and release ACh molecules into the synaptic cleft via exocytosis after depolarization. AChRs are localized opposite the presynaptic terminals by protein scaffolds at the postjunctional folds of the sarcolemma, dystrophin, a structural protein, connects the sarcomere, sarcolemma, and extracellular matrix components. Rapsyn is another protein that docks AChRs and structural proteins to the cytoskeleton, also present is the receptor tyrosine kinase protein MuSK, a signaling protein involved in the development of the neuromuscular junction, which is also held in place by rapsyn. The neuromuscular junction is where a neuron activates a muscle to contract and this influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neurons cell membrane through SNARE proteins. Fusion of the membrane with the presynaptic cell membrane results in the emptying of the vesicles contents into the synaptic cleft. Acetylcholine diffuses into the cleft and can bind to the nicotinic acetylcholine receptors on the motor endplate. Acetylcholine is a neurotransmitter synthesized from choline and acetyl-CoA, and is involved in the stimulation of muscle tissue in vertebrates as well as in some invertebrate animals. In vertebrate animals, the receptor subtype that is found at the neuromuscular junction of skeletal muscles is the nicotinic acetylcholine receptor. Each subunit of this receptor has a characteristic “cys-loop, ” which is composed of a cysteine residue followed by 13 amino acid residues, the two cysteine residues form a disulfide linkage which results in the “cys-loop” receptor that is capable of binding acetylcholine and other ligands. These cys-loop receptors are only in eukaryotes, but prokaryotes possess ACh receptors with similar properties
25.
Chemical synapse
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Chemical synapses are biological junctions through which neurons signals can be exchanged to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the nervous system. They are crucial to the computations that underlie perception and thought. They allow the system to connect to and control other systems of the body. At a chemical synapse, one neuron releases neurotransmitter molecules into a space that is adjacent to another neuron. The neurotransmitters are kept within small sacs called vesicles, and are released into the synaptic cleft by exocytosis and these molecules then bind to receptors on the postsynaptic cells side of the synaptic cleft. The adult human brain is estimated to contain from 1014 to 5 ×1014 synapses, every cubic millimeter of cerebral cortex contains roughly a billion of them. The word synapse comes from synaptein, which Sir Charles Scott Sherrington and colleagues coined from the Greek syn-, chemical synapses are not the only type of biological synapse, electrical and immunological synapses also exist. Without a qualifier, however, synapse commonly means chemical synapse, synapses are functional connections between neurons, or between neurons and other types of cells. A typical neuron gives rise to several thousand synapses, although there are types that make far fewer. Most synapses connect axons to dendrites, but there are other types of connections, including axon-to-cell-body, axon-to-axon. Chemical synapses pass information directionally from a cell to a postsynaptic cell and are therefore asymmetric in structure. Synaptic vesicles are docked at the plasma membrane at regions called active zones. Immediately opposite is a region of the cell containing neurotransmitter receptors. Immediately behind the postsynaptic membrane is a complex of interlinked proteins called the postsynaptic density. Proteins in the PSD are involved in anchoring and trafficking neurotransmitter receptors, the receptors and PSDs are often found in specialized protrusions from the main dendritic shaft called dendritic spines. Synapses may be described as symmetric or asymmetric, when examined under an electron microscope, asymmetric synapses are characterized by rounded vesicles in the presynaptic cell, and a prominent postsynaptic density. Symmetric synapses in contrast have flattened or elongated vesicles, and do not contain a prominent postsynaptic density, the synaptic cleft is a gap between the pre- and postsynaptic cells that is about 20 nm wide
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Cholinergic
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In general, the word choline refers to the various quaternary ammonium salts containing the N, N, N-trimethylethanolammonium cation. Found in most animal tissues, choline is a component of the neurotransmitter acetylcholine. It prevents fat deposits in the liver and facilitates the movement of fats into the cells, the richest sources of choline are liver, kidney, brain, wheat germ, brewers yeast, and egg yolk. Neurologically, cholinergic is the term referring to acetylcholine. The parasympathetic nervous system, which uses acetylcholine almost exclusively to send its messages, is said to be almost entirely cholinergic, neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, the basal forebrain, and brain stem complexes are also cholinergic. In addition, the receptor for the sweat glands are also cholinergic. Such mimics are called parasympathomimetic drugs or cholinomimetic drugs, a receptor is cholinergic if it uses acetylcholine as its neurotransmitter. A synapse is cholinergic if it uses acetylcholine as its neurotransmitter, a molecule must possess a nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt. For maximum potency, the size of the alkyl groups substituted on the nitrogen should not exceed the size of a methyl group, the molecule should have an oxygen atom, preferably an ester-like oxygen capable of participating in a hydrogen bond. The hypothesis states that a cause of AD is the reduced synthesis of acetylcholine. Many current drug therapies for AD are centered on the cholinergic hypothesis, studies performed in the 1980s demonstrated significant impairment of cholinergic markers in Alzheimer’s patients. Scopolamine, a drug, was used to block cholinergic activity in young adults. The memory impairments were reversed when treated with physostigmine, a cholinergic agonist, however, reversing memory impairments in AD patients may not be this easy due to permanent changes in brain structure. When young adults perform memory and attention tasks, brain activation patterns are balanced between the frontal and occipital lobes, creating a balance between bottom-up and top-down processing. Normal cognitive aging may affect long term and working memory, though the cholinergic system, adults with AD presenting with dysfunction of the cholinergic system are not able to compensate for long-term and working memory deficits. AD is currently treated by increasing acetylcholine concentration by using acetylcholinesterase inhibitors to inhibit acetylcholinesterase from breaking down acetylcholine, current acetylcholinesterase inhibitors approved in the United States by the FDA to treat Alzheimer’s include donepezil, rivastigmine, and galantamine. These drugs work to increase the levels of acetylcholine and subsequently increase the function of neural cells, however, not all treatments based upon the cholinergic hypothesis have been successful in treating the symptoms or slowing the progression of AD. Therefore, a disruption to the system has been proposed as a consequence of AD rather than a direct cause
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Neurotransmission
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Neurotransmission is essential for the process of communication between two neurons. In response to an action potential or graded electrical potential. The released neurotransmitter may then move across the synapse to be detected by, binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way. Neurons form elaborate networks through which nerve impulses travel, each neuron has as many as 15,000 connections with other neurons. Neurons do not touch each other, instead, neurons interact at close contact points called synapses, a neuron transports its information by way of an action potential. When the nerve impulse arrives at the synapse, it may cause the release of neurotransmitters, the postsynaptic neuron may receive inputs from many additional neurons, both excitatory and inhibitory. Excitatory inputs bring a neuron closer to threshold, while inhibitory inputs bring the neuron farther from threshold, an action potential is an all-or-none event, neurons whose membranes have not reached threshold will not fire, while those that do must fire. Once the action potential is initiated, it will propagate along the axon and this can take place in the cell body, in the axon, or in the axon terminal. Storage of the neurotransmitter in storage granules or vesicles in the axon terminal, calcium enters the axon terminal during an action potential, causing release of the neurotransmitter into the synaptic cleft. After its release, the transmitter binds to and activates a receptor in the postsynaptic membrane, the neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed. Neurotransmitters are spontaneously packed in vesicles and released in individual quanta-packets independently of presynaptic action potentials and this slow release is detectable and produces micro-inhibitory or micro-excitatory effects on the postsynaptic neuron. An action potential briefly amplifies this process, neurotransmitter containing vesicles cluster around active sites, and after they have been released may be recycled by one of three proposed mechanism. The first proposed mechanism involves partial opening and then re-closing of the vesicle, the second two involve the full fusion of the vesicle with the membrane, followed by recycling, or recycling into the endosome. The vesicle exocytosis is through to be driven by a complex called SNARE. Once released, a neurotransmitter enters the synapse and encounters receptors, neurotransmitters receptors can either be inotropic or g protein coupled. Inotropic receptors allow for ions to pass through when agonized by a ligand, the main model involves a receptor composed of multiple subunits that allow for coordination of ion preference. G protein coupled receptors, also called metabotropic receptors, when bound to by a ligand undergo conformational changes yielding in intracellular response, termination of neurotransmitter activity is usually done by a transporter, however enzymatic deactivation is also plausible. Each neuron connects with other neurons, receiving numerous impulses from them
28.
Carboxylesterase family
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Carboxylesterase, type B is a family of evolutionarily related proteins. Higher eukaryotes have many distinct esterases, the different types include those that act on carboxylic esters. Carboxyl-esterases have been classified into three categories on the basis of differential patterns of inhibition by organophosphates, the sequence of a number of type-B carboxylesterases indicates that the majority are evolutionarily related. As is the case for lipases and serine proteases, the apparatus of esterases involves three residues, a serine, a glutamate or aspartate and a histidine. This family belongs to the superfamily of proteins with the Alpha/beta hydrolase fold
29.
Organophosphorus compound
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Organophosphorus compounds are organic compounds containing phosphorus. They are used primarily in pest control as an alternative to chlorinated hydrocarbons that persist in the environment, organophosphorus chemistry is the corresponding science of the properties and reactivity of organophosphorus compounds. Phosphorus, like nitrogen, is in group 15 of the periodic table and these compounds are highly effective insecticides, though some are also lethal to humans at minuscule doses and include some of the most toxic substances ever created by man. The definition of organophosphorus compounds is variable, which can lead to confusion, in industrial and environmental chemistry, an organophosphorus compound need contain only an organic substituent, but need not have a direct phosphorus-carbon bond. Thus a large proportion of pesticides, are included in this class of compounds. In a descriptive but only intermittently used nomenclature, phosphorus compounds are identified by their coordination number δ, in this system, a phosphine is a δ3λ3 compound. Phosphate esters have the general structure P3 feature P, such species are of technological importance as flame retardant agents, and plasticizers. Lacking a P−C bond, these compounds are in the technical sense not organophosphorus compounds, many derivatives are found in nature, such as phosphatidylcholine. Phosphate ester are synthesized by alcoholysis of phosphorus oxychloride, a variety of mixed amido-alkoxo derivatives are known, one medically significant example being the anti-cancer drug cyclophosphamide. Also derivatives containing the group include the pesticide malathion. The organophosphates prepared on the largest scale are the zinc dithiophosphates, several million kilograms of this coordination complex are produced annually by the reaction of phosphorus pentasulfide with alcohols. In the environment, these compounds break down via hydrolysis to eventually afford phosphate, phosphonates are esters of phosphonic acid and have the general formula RP2. Phosphonates have many applications, a well-known member being glyphosate. With the formula 2PCH2NHCH2CO2H, this derivative of glycine is one of the most widely used herbicides, bisphosphonates are a class of drugs to treat osteoporosis. The nerve gas agent sarin, containing both C–P and F–P bonds, is a phosphonate, phosphinates feature two P–C bonds, with the general formula R2P. A commercially significant member is the herbicide Glufosinate, similar to glyphosate mentioned above, it has the structure CH3PCH2CH2CHCO2H. The Michaelis–Arbuzov reaction is the method for the synthesis of these compounds. For example, dimethylmethylphosphonate arises from the rearrangement of trimethylphosphite, which is catalyzed by methyl iodide, in the Horner–Wadsworth–Emmons reaction and the Seyferth–Gilbert homologation, phosphonates are used in reactions with carbonyl compounds
30.
Nerve agent
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Nerve agents are a class of phosphorus-containing organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by blocking acetylcholinesterase, an enzyme that catalyzes the breakdown of acetylcholine, some nerve agents are readily vaporized or aerosolized, and the primary portal of entry into the body is the respiratory system. Nerve agents can also be absorbed through the skin, requiring that those likely to be subjected to such agents wear a body suit in addition to a respirator. As their name suggests, nerve agents attack the system of the human body. All such agents function the way, by inhibiting the enzyme acetylcholinesterase. ACh gives the signal for muscles to contract, thus, if it cannot be broken down, initial symptoms following exposure to nerve agents are a runny nose, tightness in the chest, and constriction of the pupils. Soon after, the victim will then have difficulty breathing and will experience nausea, as the victim continues to lose control of their bodily functions, they will involuntarily salivate, lacrimate, urinate, defecate, and experience gastrointestinal pain and vomiting. Blisters and burning of the eyes and/or lungs may also occur and this phase is followed by initially myoclonic jerks followed by status epilepticus. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the junction of the diaphragm. The effects of agents are long lasting and increase with continued exposure. Survivors of nerve agent poisoning almost invariably suffer chronic neurological damage and this neurological damage can also lead to continuing psychiatric effects. When a normally functioning motor nerve is stimulated, it releases the neurotransmitter acetylcholine, once the impulse is sent, the enzyme acetylcholinesterase immediately breaks down the acetylcholine in order to allow the muscle or organ to relax. Nerve agents disrupt the system by inhibiting the function of the enzyme acetylcholinesterase by forming a covalent bond where acetylcholine would break down. Acetylcholine thus builds up and continues to act so that any nerve impulses are continually transmitted and this same action also occurs at the gland and organ levels, resulting in uncontrolled drooling, tearing of the eyes and excess production of mucus from the nose. The structures of the complexes of soman with acetylcholinesterase from Torpedo californica have been solved by X-Ray crystallography, the mechanism of action of soman could be seen on example of 2wfz. Atropine and related anticholinergic drugs act as antidotes to nerve agent poisoning because they block acetylcholine receptors, while these drugs will save the life of a person affected with nerve agents, that person may be incapacitated briefly or for an extended period, depending on the amount of exposure. The endpoint of atropine administration is the clearing of bronchial secretions, atropine for field use by military personnel is often loaded in an autoinjector, for ease of use in stressful conditions. Pralidoxime chloride, also known as 2-PAM chloride, is used as an antidote
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Pesticide
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Pesticides are substances that are meant to control pests or weeds. The most common of these are herbicides which account for approximately 80% of all pesticide use, most pesticides are intended to serve as plant protection products, which in general, protect plants from weeds, fungi, or insects. In general, a pesticide is a chemical or biological agent that deters, incapacitates, kills, or otherwise discourages pests. Target pests can include insects, plant pathogens, weeds, mollusks, birds, mammals, fish, nematodes, although pesticides have benefits, some also have drawbacks, such as potential toxicity to humans and other species. According to the Stockholm Convention on Persistent Organic Pollutants,9 of the 12 most dangerous, the term includes substances intended for use as a plant growth regulator, defoliant, desiccant, or agent for thinning fruit or preventing the premature fall of fruit. Also used as substances applied to either before or after harvest to protect the commodity from deterioration during storage. Pesticides can be classified by target organism, chemical structure, biopesticides include microbial pesticides and biochemical pesticides. Plant-derived pesticides, or botanicals, have been developing quickly and these include the pyrethroids, rotenoids, nicotinoids, and a fourth group that includes strychnine and scilliroside. Many pesticides can be grouped into chemical families, prominent insecticide families include organochlorines, organophosphates, and carbamates. Organochlorine hydrocarbons could be separated into dichlorodiphenylethanes, cyclodiene compounds, and they operate by disrupting the sodium/potassium balance of the nerve fiber, forcing the nerve to transmit continuously. Their toxicities vary greatly, but they have phased out because of their persistence. Organophosphate and carbamates largely replaced organochlorines, both operate through inhibiting the enzyme acetylcholinesterase, allowing acetylcholine to transfer nerve impulses indefinitely and causing a variety of symptoms such as weakness or paralysis. Organophosphates are quite toxic to vertebrates, and have in some cases replaced by less toxic carbamates. Thiocarbamate and dithiocarbamates are subclasses of carbamates, prominent families of herbicides include phenoxy and benzoic acid herbicides, triazines, ureas, and Chloroacetanilides. Phenoxy compounds tend to selectively kill broad-leaf weeds rather than grasses, the phenoxy and benzoic acid herbicides function similar to plant growth hormones, and grow cells without normal cell division, crushing the plants nutrient transport system. Many commonly used pesticides are not included in these families, including glyphosate, Pesticides can be classified based upon their biological mechanism function or application method. Most pesticides work by poisoning pests, a systemic pesticide moves inside a plant following absorption by the plant. With insecticides and most fungicides, this movement is usually upward and outward, increased efficiency may be a result
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Hydrolysis
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Hydrolysis usually means the cleavage of chemical bonds by the addition of water. When a carbohydrate is broken into its component sugar molecules by hydrolysis, generally, hydrolysis or saccharification is a step in the degradation of a substance. Hydrolysis can be the reverse of a reaction in which two molecules join together into a larger one and eject a water molecule. Thus hydrolysis adds water to break down, whereas condensation builds up by removing water, usually hydrolysis is a chemical process in which a molecule of water is added to a substance. Sometimes this addition causes both substance and water molecule to split into two parts, in such reactions, one fragment of the target molecule gains a hydrogen ion. A common kind of hydrolysis occurs when a salt of an acid or weak base is dissolved in water. Water spontaneously ionizes into hydroxide anions and hydronium cations, the salt also dissociates into its constituent anions and cations. For example, sodium acetate dissociates in water into sodium and acetate ions, sodium ions react very little with the hydroxide ions whereas the acetate ions combine with hydronium ions to produce acetic acid. In this case the net result is an excess of hydroxide ions. For example, dissolving sulfuric acid in water is accompanied by hydrolysis to give hydronium and bisulfate, for a more technical discussion of what occurs during such a hydrolysis, see Brønsted–Lowry acid–base theory. Acid–base-catalysed hydrolyses are very common, one example is the hydrolysis of amides or esters and their hydrolysis occurs when the nucleophile attacks the carbon of the carbonyl group of the ester or amide. In an aqueous base, hydroxyl ions are better nucleophiles than polar molecules such as water, in acids, the carbonyl group becomes protonated, and this leads to a much easier nucleophilic attack. The products for both hydrolyses are compounds with carboxylic acid groups, perhaps the oldest commercially practiced example of ester hydrolysis is saponification. It is the hydrolysis of a triglyceride with a base such as sodium hydroxide. During the process, glycerol is formed, and the fatty acids react with the base and these salts are called soaps, commonly used in households. In addition, in living systems, most biochemical reactions take place during the catalysis of enzymes, the catalytic action of enzymes allows the hydrolysis of proteins, fats, oils, and carbohydrates. As an example, one may consider proteases and they catalyse the hydrolysis of interior peptide bonds in peptide chains, as opposed to exopeptidases. However, proteases do not catalyse the hydrolysis of all kinds of proteins and their action is stereo-selective, Only proteins with a certain tertiary structure are targeted as some kind of orienting force is needed to place the amide group in the proper position for catalysis
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Diffusion
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Diffusion is the net movement of molecules or atoms from a region of high concentration to a region of low concentration. This is also referred to as the movement of a substance down a concentration gradient, a gradient is the change in the value of a quantity with the change in another variable. The word diffusion derives from the Latin word, diffundere, which means to spread out, a distinguishing feature of diffusion is that it results in mixing or mass transport, without requiring bulk motion. Thus, diffusion should not be confused with convection, or advection, an example of a situation in which bulk flow and diffusion can be differentiated is the mechanism by which oxygen enters the body during external respiration. The lungs are located in the cavity, which expands as the first step in external respiration. This expansion leads to an increase in volume of the alveoli in the lungs and this creates a pressure gradient between the air outside the body and the alveoli. The air moves down the gradient through the airways of the lungs and into the alveoli until the pressure of the air. The air arriving in the alveoli has a concentration of oxygen than the “stale” air in the alveoli. The increase in oxygen concentration creates a concentration gradient for oxygen between the air in the alveoli and the blood in the capillaries that surround the alveoli, oxygen then moves by diffusion, down the concentration gradient, into the blood. The other consequence of the air arriving in alveoli is that the concentration of carbon dioxide in the alveoli decreases and this creates a concentration gradient for carbon dioxide to diffuse from the blood into the alveoli. The pumping action of the heart then transports the blood around the body, as the left ventricle of the heart contracts, the volume decreases, which increases the pressure in the ventricle. This creates a gradient between the heart and the capillaries, and blood moves through blood vessels by bulk flow. The concept of diffusion is widely used in, physics, chemistry, biology, sociology, economics, however, in each case, the object that is undergoing diffusion is “spreading out” from a point or location at which there is a higher concentration of that object. In the phenomenological approach, diffusion is the movement of a substance from a region of high concentration to a region of low concentration without bulk motion, according to Ficks laws, the diffusion flux is proportional to the negative gradient of concentrations. It goes from regions of higher concentration to regions of lower concentration, some time later, various generalizations of Ficks laws were developed in the frame of thermodynamics and non-equilibrium thermodynamics. From the atomistic point of view, diffusion is considered as a result of the walk of the diffusing particles. In molecular diffusion, the molecules are self-propelled by thermal energy. Random walk of small particles in suspension in a fluid was discovered in 1827 by Robert Brown, the theory of the Brownian motion and the atomistic backgrounds of diffusion were developed by Albert Einstein
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Active site
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In biology, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of residues that form bonds with the substrate. The active site is usually a groove or pocket of the enzyme which can be located in a tunnel within the enzyme. An active site can catalyse a reaction repeatedly as its residues are not altered at the end of the reaction, usually, an enzyme molecule has only one active site, and the active site fits with one specific type of substrate. An active site contains a site that binds the substrate. Residues in the site form hydrogen bonds, hydrophobic interactions. In order to function, the site needs to be in a specific conformation. A tighter fit between a site and the substrate molecule is believed to increase efficiency of a reaction. Most enzymes have deeply buried active sites, which can be accessed by a substrate via access channels, there are two proposed models of how enzymes fit to their specific substrate, the lock and key model and the induced fit model. Emil Fischers lock and key model assumes that the site is a perfect fit for a specific substrate. Daniel Koshlands theory of enzyme-substrate binding is that the active site, the induced fit model is a development of the lock-and-key model and assumes that an active site is flexible and it changes shape until the substrate is completely bound. The substrate is thought to induce a change in the shape of the active site, the hypothesis also predicts that the presence of certain residues in the active site will encourage the enzyme to locate the correct substrate. Conformational changes may occur as the substrate is bound. After the products of the move away from the enzyme. Once the substrate is bound and oriented in the active site, the residues of the catalytic site are typically very close to the binding site, and some residues can have dual-roles in both binding and catalysis. Catalytic residues of the site interact with the substrate to lower the energy of a reaction. They do this by a number of different mechanisms, firstly, they can act as donors or acceptors of protons or other groups on the substrate to facilitate the reaction. They can also form electrostatic interactions to stabilise charge buildup on the state or leaving group
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Amine
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In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group, important amines include amino acids, biogenic amines, trimethylamine, and aniline, see Category, Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine, see Category, compounds with a nitrogen atom attached to a carbonyl group, thus having the structure R–CO–NR′R″, are called amides and have different chemical properties from amines. An aliphatic amine has no aromatic ring attached directly to the nitrogen atom, aromatic amines have the nitrogen atom connected to an aromatic ring as in the various anilines. The aromatic ring decreases the alkalinity of the amine, depending on its substituents, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. Amines are organized into four subcategories, Primary amines — Primary amines arise when one of three atoms in ammonia is replaced by an alkyl or aromatic. Important primary alkyl amines include, methylamine, most amino acids, Secondary amines — Secondary amines have two organic substituents bound to the nitrogen together with one hydrogen. Important representatives include dimethylamine, while an example of an aromatic amine would be diphenylamine, tertiary amines — In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a fishy smell. Cyclic amines — Cyclic amines are either secondary or tertiary amines, examples of cyclic amines include the 3-membered ring aziridine and the six-membered ring piperidine. N-methylpiperidine and N-phenylpiperidine are examples of tertiary amines. It is also possible to have four organic substituents on the nitrogen and these species are not amines but are quaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds of anions, Amines are named in several ways. Typically, the compound is given the prefix amino- or the suffix, the prefix N- shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine, systematic names for some common amines, Hydrogen bonding significantly influences the properties of primary and secondary amines. Thus the melting point and boiling point of amines is higher than those of the corresponding phosphines, for example, methyl and ethyl amines are gases under standard conditions, whereas the corresponding methyl and ethyl alcohols are liquids. Amines possess a characteristic smell, liquid amines have a distinctive fishy smell. The nitrogen atom features a lone pair that can bind H+ to form an ammonium ion R3NH+
. PMID 9742217. 
