CYP3A5

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Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.

Tissue distribution

CYP3A5 encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the Cytochrome P450, the CYP3A5 is expressed in the prostate and the liver.[1] It is also expressed in epithelium of the small intestine and large intestine for uptake and in small amounts in the bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level).[1]

Clinical significance

The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. The enzyme metabolizes drugs such as nifedipine and cyclosporine as well as the steroid hormones testosterone, progesterone and androstenedione. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. This cluster includes a pseudogene, CYP3A5P1, which is very similar to CYP3A5. This similarity has caused some difficulty in determining whether cloned sequences represent the gene or the pseudogene.[2]

CYP3A4/3A5 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.[1] Immunoblot analysis of liver microsomes showed that CYP3A5 is expressed as a 52.5-kD protein, whereas CYP3A4 migrates as a 52.0-kD protein.[3] The human CYP3A subfamily, CYP3A4, CYP3A5, CYP3A7 and CYP3A43, is one of the most versatile of the biotransformation systems that facilitate the elimination of drugs (37% of the 200 most frequently prescribed drugs in the U.S.[4]

CYP3A4 and CYP3A5 together account for approximately 30% of hepatic cytochrome P450, and approximately half of medications that are oxidatively metabolized by P450 are CYP3A substrates.[5] Both CYP3A4 and CYP3A5 are expressed in liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues.[5]

Allele distribution

The CYP3A5 gene has several functional variants, which vary depending on ethnicity. The CYP3A5*1 allele is associated with a normal metabolization of medication. It is most common among individuals native to Sub-Equatorial Africa, though the mutation also occurs at low frequencies in other populations. The CYP3A5*3 allele is linked with a poor metabolization of medication. It is near fixation in Europe, and is likewise found at high frequencies in West Asia and Central Asia, as well as among Afro-Asiatic (Hamitic-Semitic) speaking populations in North Africa and the Horn of Africa. Additionally, the mutation occurs at moderate-to-high frequencies in South Asia, Southeast Asia and East Asia, and at low frequencies in Sub-Equatorial Africa.[6][7]

Global distribution of the CYP3A5 alleles:[7]

Population CYP3A5*1 CYP3A5*3 CYP3A5*6 CYP3A5*7
Adygei 12% 88%
Afar 35% 65% 18% 0%
African Americans 63% 37% 12% 21%
Algerians (North) 19% 81% 5% 1%
Amhara 33% 67% 15% 0%
Anatolian Turks 9% 91% 0% 0%
Armenians (South) 5% 95% 0% 0%
Asante 89% 11% 22% 7%
Ashkenazi Jews 3% 97% 0% 0%
Balochi 20% 80%
Bantu (Kenya) 83% 17%
Bantu (South Africa) 74% 26% 18% 10%
Bantu (Uganda) 96% 4% 22% 21%
Basques (French) 4% 96%
Bedouin (Israel) 17% 83%
Berbers (Morocco) 20% 80% 4% 1%
Biaka Pygmies 89% 11%
Brahui 12% 88%
Britons (England and Scotland) 35% 65% 0%
Bulsa 81% 19% 16% 13%
Burusho 22% 78%
Cameroonian (Lake Chad) 76% 24% 32% 7%
Canadian Caucasians 7% 93% 0% 0%
Chagga 74% 26% 14% 9%
Chewa 85% 15% 16% 17%
Chinese 25% 75% 0%
Chinese (Denver, Colorado) 25% 75%
Colombians 15% 85%
Colombians (Medellian) 48% 52% 2%
Congolese (Brazzaville) 80% 20% 12% 9%
Dai 45% 55%
Druze 8% 92%
Daur 15% 85%
East Asian 31% 69% 0% 0%
European 2% 98% 0% 0%
Finns 45% 55% 0%
French 8%-9% 91%-92% 0% 0%
Gabonese 79% 21% 19% 19%
Gambians 79% 21% 20% 12%
Germans 7% 93%
Gujarati (Houston, Texas) 25% 75%
Han 25% 75%
Han (Beijing) 28% 72% 0%
Han (Southern) 47% 53% 0%
Hazara 25% 75%
Hezhen 15% 85%
Hispanic 25% 75% 0% 0%
Iberians 39% 61% 0%
Igbo 87% 13% 18% 9%
Indians 41% 59% 0%
Italians (Bergamo) 18% 82%
Italians (Sardinia) 5% 95%
Italians (Tuscany) 5%-6% 94%-95% 0.5%
Japanese 23% 77% 0%
Japanese (Tokyo) 26% 74% 0.004%
Kalash 24% 76%
Karitiana 23% 77%
Kasena 78% 22% 17% 13%
Khmer 27% 73%
Koreans 19% 81% 0%
Kotoko 73% 27% 23% 5%
Lahu 25% 75%
Lemba 87% 13% 25% 15%
Lomwe 83% 17% 22% 11%
Luhya (Webuye, Kenya) 86% 14% 26%
Maale 51% 49% 15% 1%
Maasai (Kinyawa, Kenya) 51% 49% 14%
Makrani 14% 86%
Malay 39% 61% 0%
Malawians 79% 21% 14% 14%
Mandenka 69% 31%
Manjak 79% 21% 23% 7%
Maya 29% 71%
Mayo Darle 73% 27% 25% 6%
Mbuti Pygmies 93% 7%
Melanesians 18% 82%
Mestizo (El Salvador and Nicaragua) 24% 76%
Mestizo (Ecuador) 12% 88%
Mexicans (Los Angeles) 25% 75% 2%
Miaozu 35% 65%
Mongola 35% 65%
Mozabite 16% 84%
Naxi 28% 72%
Ngoni 89% 11% 33% 6%
North American Caucasians 9% 90%
Orogen 10% 90%
Orcadians 16% 84%
Oromo 35% 65% 14% 0%
Papuans 21% 79%
Palestinians 18% 82%
Pathan 12% 88%
Pima 54% 46%
Puerto Ricans 56% 44% 5%
Russians 8% 92%
San (Namibia) 93% 7%
Sena 84% 16% 23% 16%
Sephardi Jews 11% 89% 0% 0%
She 45% 55%
Shewa Arabs 60% 40% 22% 7%
Shona 22% 78% 22% 10%
Sindhi 18% 82%
Somie (Cameroonian Grassfields) 77% 23% 18% 10%
Southern Sudanese 76% 24% 33% 3%
Spaniard 9% 91%
Sudanese (Northern) 40% 60% 11% 0%
Sudanese (Kordofan) 55% 45% 20% 2%
Surui 17% 83%
Swedes 7% 93% 0% 0%
Tanzanians 81% 19% 19% 12%
Tu 10% 90%
Tujia 35% 65%
Tunisian 19% 81% 1% 0%
Uygur 5% 95%
Wolof 73% 27% 18% 9%
Xibo 22% 78%
Yao 82% 18% 13% 9%
Yakuts 10% 90%
Yemeni (Hadramaut) 15% 85% 3% 1%
Yemeni (Sena and Msila) 42% 58% 12% 3%
Yizu 20% 80%
Yoruba 83%-94% 6%-17% 17%-75% 0%
Zimbabweans (Mposi) 84% 16% 16% 19%

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|{{{bSize}}}px|alt=Irinotecan Pathway edit]]
  1. The interactive pathway map can be edited at WikiPathways: Lua error in package.lua at line 80: module 'strict' not found.

See also

References

  1. 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
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  5. 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
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  7. 7.0 7.1 Lua error in package.lua at line 80: module 'strict' not found.

External links

Further reading

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