P450scc
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P450scc
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones. P450scc is a member of the cytochrome P450 superfamily of enzymes (family 11, subfamily A, polypeptide 1) and is encoded by the gene. Nomenclature The systematic name of this enzyme class is cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving). Other names include: * C27-side-chain cleavage enzyme * cholesterol 20-22-desmolase * cholesterol C20-22 desmolase * cholesterol desmolase * cholesterol side-chain cleavage enzyme * cholesterol side-chain-cleaving enzyme * cytochrome P-450scc * desmolase, steroid 20-22 * enzymes, cholesterol side-chain-cleaving * steroid 20-22 desmolas ...
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Adrenodoxin Reductase
Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in steroid hormone biosynthesis. Examination of complete genome sequences revealed that adrenodoxin reductase gene is present in most metazoans and prokaryotes. Nomenclature The name of the enzyme was coined based on its function to reduce a Fe-2S(2 iron, 2 sulfur) electron-transfer protein that was named adrenodoxin. Later, in some studies, the enzyme was also referred to as a "ferredoxin reductase", as adrenodoxin is a ferredoxin. In the human gene nomenclature, the standard name is ferredoxin reductase and the symbol is FDXR, with ADXR specified as a synonym. The assignment of the name "ferredoxin reductase" has been criticized as a misnomer because determination of the structure of adrenodoxin reductase revealed that it is completely ...
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Adrenodoxin
Adrenal ferredoxin (also adrenodoxin (ADX), adrenodoxin, mitochondrial, hepatoredoxin, ferredoxin-1 (FDX1)) is a protein that in humans is encoded by the ''FDX1'' gene. In addition to the expressed gene at this chromosomal locus (11q22), there are pseudogenes located on chromosomes 20 and 21. Function Adrenodoxin is a small iron-sulfur protein that can accept and carry a single electron. Adrenodoxin functions as an electron transfer protein in the mitochondrial cytochrome P450 systems. The first enzyme in this system is adrenodoxin reductase that carries an FAD. FAD can be reduced by two electrons donated from coenzyme NADPH. These two electrons are transferred one a time to adrenodoxin. Adrenodoxin in return reduces mitochondrial cytochrome P450. This particular oxidation/reduction system is involved in the synthesis of steroid hormones in steroidogenic tissues. In addition, similar systems also function in vitamin D and bile acid Bile acids are steroid acids found predomina ...
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Steroidogenic Factor 1
The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered. Structure The ''NR5A1'' gene encodes a 461-amino acid protein that shares several conserved domains consistent with members of the nuclear receptor subfamily. The N-terminal domain includes two zinc fingers and is responsible for DNA binding via specific recognition of target sequences. Variations of AGGTCA DNA motifs allows SF-1 to interact with the major groove of the DNA helix and monomerically bind. Following binding, trans-activation of target genes depends on recru ...
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Corticotropin
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a Peptide, polypeptide tropic hormone produced by and secreted by the Anterior pituitary, anterior pituitary gland. It is also used as a Adrenocorticotropic hormone (medication), medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol by the Adrenal cortex, cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is an indicator of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing ...
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Pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocorticoids. In addition, pregnenolone is biologically active in its own right, acting as a neurosteroid. In addition to its role as a natural hormone, pregnenolone has been used as a medication and supplement; for information on pregnenolone as a medication or supplement, see the pregnenolone (medication) article. Biological function Pregnenolone and its 3β-sulfate, pregnenolone sulfate, like DHEA, DHEA sulfate, and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization. Pregnenolone and its sulfate ester may improve cognitive and memory function. In additi ...
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Corticotropin
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a Peptide, polypeptide tropic hormone produced by and secreted by the Anterior pituitary, anterior pituitary gland. It is also used as a Adrenocorticotropic hormone (medication), medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol by the Adrenal cortex, cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is an indicator of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing ...
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Steroidogenic Acute Regulatory Protein
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is primarily present in steroid-producing cells, including theca cells and luteal cells in the ovary, Leydig cells in the testis and cell types in the adrenal cortex. Function Cholesterol needs to be transferred from the outer mitochondrial membrane to the inner membrane where cytochrome P450scc enzyme (CYP11A1) cleaves the cholesterol side chain, which is the first enzymatic step in all steroid synthesis. The aqueous phase between these two membranes cannot be crossed by the lipophilic cholesterol, unless certain proteins assist in this process. A number of proteins have historically been proposed to facilitate this transfer including: sterol carrier protein 2 (SCP2), steroidogenic activator polypeptide (SAP), peripheral benzodiazepine recep ...
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Cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance (pharmacology), clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Ronald W. Estabrook, Estabrook, David Y. Cooper, Cooper, and Otto Rosenthal, Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of secondary metabolite, defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdom (biology), kingdoms of life: animals, plants, fungus, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins ...
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Ternary Complex
A ternary complex is a protein complex containing three different molecules that are bound together. In structural biology, ''ternary complex'' can also be used to describe a crystal containing a protein with two small molecules bound, for example cofactor and substrate; or a complex formed between two proteins and a single substrate. In Immunology, ''ternary complex'' can refer to the MHC–peptide–T-cell-receptor complex formed when T cells recognize epitopes of an antigen. Some other example can be taken like ternary complex while eukaryotic translation, in which ternary complex is composed of eIF-3 & eIF-2 + Ribosome 40s subunit+ tRNAi. A ternary complex can be a complex formed between two substrate molecules and an enzyme. This is seen in multi-substrate enzyme-catalyzed reactions where two substrates and two products can be formed. The ternary complex is an intermediate between the product formation in this type of enzyme-catalyzed reactions. An example for a ternary compl ...
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Gene Expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication. The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, '' ...
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Transcription Factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA ...
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Side Chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a larger hydrocarbon backbone. It is one factor in determining a molecule's properties and reactivity. A side chain is also known as a pendant chain, but a pendant group (side group) has a different definition. Conventions The placeholder R is often used as a generic placeholder for alkyl (saturated hydrocarbon) group side chains in chemical structure diagrams. To indicate other non-carbon groups in structure diagrams, X, Y, or Z are often used. History The ''R'' symbol was introduced by 19th-century French chemist Charles Frédéric Gerhardt, who advocated its adoption on the grounds that it would be widely recognizable and intelligible given its correspondence in multiple European languages to the initial letter of "root" or "residue": ...
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