CYP7B1

Last updated
CYP7B1
Identifiers
Aliases CYP7B1 , CBAS3, CP7B, SPG5A, cytochrome P450 family 7 subfamily B member 1
External IDs OMIM: 603711 MGI: 104978 HomoloGene: 3544 GeneCards: CYP7B1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004820
NM_001324112

NM_007825

RefSeq (protein)

NP_001311041
NP_004811

NP_031851

Location (UCSC) Chr 8: 64.59 – 64.8 Mb Chr 3: 18.13 – 18.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1 gene. [5] [6] [7] This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

Contents

Function

This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. [7]

CYP7B was discovered by Stapleton [8] in a screen for transcripts expressed differentially in rat hippocampus versus the remainder of the brain. The encoded polypeptide, initially designated hct-1 (hippocampus transcript 1), had significant homology with CYP7A1. [8] The protein was designated CYP7B1 by the P450 Nomenclature Committee. Expression of the recombinant protein demonstrated 7alpha-hydroxylation activity for steroids (DHEA, pregnenolone) and oxysterols including 25-hydroxycholesterol and 27-hydroxycholesterol, [9] [10] [11] confirmed by knockout in mouse that abolished oxysterol hydroxylation in liver [12] and brain and steroid hydroxylation in multiple tissues. [13] Reporter tagging of the Cyp7b1 gene demonstrated that the enzyme is widely expressed, particularly strongly in brain, liver, kidney, heart, and spleen. [13]

Related Research Articles

<span class="mw-page-title-main">Cytochrome P450</span> Class of enzymes

Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and 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 defensive compounds, fatty acids, and hormones.

<span class="mw-page-title-main">Aldosterone synthase</span> Protein-coding gene in the species Homo sapiens

Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.

<span class="mw-page-title-main">CYP27A1</span> Protein-coding gene in the species Homo sapiens

CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.

<span class="mw-page-title-main">Cholesterol side-chain cleavage enzyme</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">Cholesterol 7 alpha-hydroxylase</span> Protein-coding gene in the species Homo sapiens

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

<span class="mw-page-title-main">21-Hydroxylase</span> Human enzyme that hydroxylates steroids

Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.

<span class="mw-page-title-main">Steroid 11β-hydroxylase</span> Protein found in mammals

Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.

In enzymology, a 24-hydroxycholesterol 7alpha-hydroxylase (EC 1.14.13.99) is an enzyme that catalyzes the chemical reaction

In enzymology, a 5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase (EC 1.14.13.96) is an enzyme that catalyzes the chemical reaction

In enzymology, a cholestanetriol 26-monooxygenase (EC 1.14.13.15) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Cholesterol 24-hydroxylase</span> Protein family

Cholesterol 24-hydroxylase, also commonly known as cholesterol 24S-hydroxylase, cholesterol 24-monooxygenase, CYP46, or CYP46A1, is an enzyme that catalyzes the conversion of cholesterol to 24S-hydroxycholesterol. It is responsible for the majority of cholesterol turnover in the human central nervous system. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating).

In enzymology, an unspecific monooxygenase (EC 1.14.14.1) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">CYP2R1</span> Mammalian protein found in Homo sapiens

CYP2R1 is cytochrome P450 2R1, an enzyme which is the principal vitamin D 25-hydroxylase. In humans it is encoded by the CYP2R1 gene located on chromosome 11p15.2. It is expressed in the endoplasmic reticulum in liver, where it performs the first step in the activation of vitamin D by catalyzing the formation of 25-hydroxyvitamin D.

<span class="mw-page-title-main">CYP39A1</span> Protein-coding gene in the species Homo sapiens

CYP39A1 also known as oxysterol 7-α-hydroxylase 2 is a protein that in humans is encoded by the CYP39A1 gene.

<span class="mw-page-title-main">Halloween genes</span> Set of genes that influence embryonic development

The halloween genes are a set of genes identified in Drosophila melanogaster that influence embryonic development. All of the genes code for cytochrome P450 enzymes in the ecdysteroidogenic pathway (biosynthesis of ecdysone from cholesterol). Ecdysteroids such as 20-hydroxyecdysone and ecdysone influence many of the morphological, physiological, biochemical changes that occur during molting in insects.

25-hydroxycholesterol 7alpha-hydroxylase (EC 1.14.13.100, 25-hydroxycholesterol 7alpha-monooxygenase, CYP7B1, CYP7B1 oxysterol 7alpha-hydroxylase) is an enzyme with systematic name cholest-5-ene-3beta,25-diol,NADPH:oxygen oxidoreductase (7alpha-hydroxylating). This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">7α-Hydroxy-DHEA</span> Chemical compound

7α-Hydroxydehydroepiandrosterone, also known as 3β,7α-dihydroxyandrost-5-ene-17-one, is an endogenous, naturally occurring steroid and a major metabolite of dehydroepiandrosterone (DHEA) that is formed by CYP7B1 in tissues such as the prostate gland and by CYP3A4 in the liver. The major metabolic pathway of DHEA outside the liver is via 7-hydroxylation into 7α-OH-DHEA and 7β-OH-DHEA. 7α-OH-DHEA has weak estrogenic activity, selectively activating the estrogen receptor ERβ. In addition, 7α-OH-DHEA may be responsible for the known antiglucocorticoid effects of DHEA.

<span class="mw-page-title-main">Steroidogenic enzyme</span>

Steroidogenic enzymes are enzymes that are involved in steroidogenesis and steroid biosynthesis. They are responsible for the biosynthesis of the steroid hormones, including sex steroids and corticosteroids, as well as neurosteroids, from cholesterol. Steroidogenic enzymes are most highly expressed in classical steroidogenic tissues, such as the testis, ovary, and adrenal cortex, but are also present in other tissues in the body.

24<i>S</i>-Hydroxycholesterol Chemical compound

24S-Hydroxycholesterol (24S-HC), also known as cholest-5-ene-3,24-diol or cerebrosterol, is an endogenous oxysterol produced by neurons in the brain to maintain cholesterol homeostasis. It was discovered in 1953 by Alberto Ercoli, S. Di Frisco, and Pietro de Ruggieri, who first isolated the molecule in the horse brain and then demonstrated its presence in the human brain.

<span class="mw-page-title-main">25-Hydroxycholesterol</span> Chemical compound

25-Hydroxycholesterol is a derivative of cholesterol, which plays a role in various biological processes in humans and other species. It is involved in cholesterol metabolism, antivirus process, inflammatory and immune response, and survival signaling pathway. 25-hydroxycholesterol is biosynthesized from cholesterol by adding a hydroxyl group at the position 25-carbon of a steroid nucleus. This reaction is catalyzed by cholesterol 25-hydroxylase, a family of enzymes that use oxygen and a di-iron cofactor to catalyze hydroxylation reaction.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000172817 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039519 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW (Dec 1998). "Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease". J Clin Invest. 102 (9): 1690–703. doi:10.1172/JCI2962. PMC   509117 . PMID   9802883.
  6. Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH (Feb 2008). "Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration". Am J Hum Genet. 82 (2): 510–5. doi:10.1016/j.ajhg.2007.10.001. PMC   2426914 . PMID   18252231.
  7. 1 2 "Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1".
  8. 1 2 Stapleton G, Steel M, Richardson M, Mason JO, Rose KA, Morris RG, Lathe R (December 1995). "A novel cytochrome P450 expressed primarily in brain". J. Biol. Chem. 270 (50): 29739–45. doi: 10.1074/jbc.270.50.29739 . PMID   8530364.
  9. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Björkhem I, Seckl J, Lathe R (May 1997). "Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 4925–30. Bibcode:1997PNAS...94.4925R. doi: 10.1073/pnas.94.10.4925 . PMC   24607 . PMID   9144166.
  10. Schwarz M, Lund EG, Lathe R, Björkhem I, Russell DW (September 1997). "Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA". J. Biol. Chem. 272 (38): 23995–4001. doi: 10.1074/jbc.272.38.23995 . PMID   9295351.
  11. Martin KO, Reiss AB, Lathe R, Javitt NB (May 1997). "7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis". J. Lipid Res. 38 (5): 1053–8. doi: 10.1016/S0022-2275(20)37229-1 . PMID   9186922.
  12. Li-Hawkins J, Lund EG, Turley SD, Russell DW (June 2000). "Disruption of the oxysterol 7alpha-hydroxylase gene in mice". J. Biol. Chem. 275 (22): 16536–42. doi: 10.1074/jbc.M001811200 . PMID   10748048.
  13. 1 2 Rose K, Allan A, Gauldie S, Stapleton G, Dobbie L, Dott K, Martin C, Wang L, Hedlund E, Seckl JR, Gustafsson JA, Lathe R (June 2001). "Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation". J. Biol. Chem. 276 (26): 23937–44. doi: 10.1074/jbc.M011564200 . PMID   11290741.

Further reading