CYP3 family | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

CYP3 family C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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CYP1, 2 and 3 family enzymes are involved in the biotransformation of xenobiotics, including clinically used drugs. CYP3A4 is the major enzyme involved in drug metabolism by the liver.

Enzymes

1339

CYP3A4 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1337

Nomenclature

CYP3A4

Previous and unofficial names

Genes

CYP3A4 (Hs)

Ensembl ID

ENSG00000160868 (Hs)

UniProtKB AC

P08684 (Hs)

EC number

1.14.14.55

1.14.14.56

Substrates

nifedipine [7]

midazolam [10]

Inhibitors

troleandomycin pK_i 7.8 [9]

ketoconazole pK_i 7.0 [4]

ritonavir pK_i >7.0 [8]

Comment

Metabolises a vast range of xenobiotics, including antidepressants, benzodiazepines, calcium channel blockers, and chemotherapeutic agents [11]. The active site is plastic, with both homotropic and heterotropic cooperativity observed with some substrates [9]. CYP3A4 catalyses the 25-hydroxylation of trihydroxycholestane [3].

CYP3A5 C Show summary »« Hide summary

Target Id

1338

Nomenclature

CYP3A5

Previous and unofficial names

cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 5 | cytochrome P450, family 3, subfamily A, polypeptide 5

Genes

CYP3A5 (Hs)

Ensembl ID

ENSG00000106258 (Hs)

UniProtKB AC

P20815 (Hs)

EC number

1.14.14.1

Inhibitors

ritonavir pK_i 6.9 [2]

Comment

CYP3A5 is expressed extrahepatically, including in the small intestine. It has overlapping substrate specificity with CYP3A4 [1,10].

CYP3A7 C Show summary »« Hide summary

Target Id

1339

Nomenclature

CYP3A7

Previous and unofficial names

cytochrome P450, subfamily IIIA, polypeptide 7 | cytochrome P450, family 3, subfamily A, polypeptide 7

Genes

CYP3A7 (Hs)

Ensembl ID

ENSG00000160870 (Hs)

UniProtKB AC

P24462 (Hs)

EC number

1.14.14.1

Comment

Fetal form, rarely expressed in adults. Has overlapping substrate specificity with CYP3A4 [1,10].

CYP3A43 C Show summary »« Hide summary

Target Id

1340

Nomenclature

CYP3A43

Previous and unofficial names

Cytochrome P450 3A43 | cytochrome P450, family 3, subfamily A, polypeptide 43

Genes

CYP3A43 (Hs)

Ensembl ID

ENSG00000021461 (Hs)

UniProtKB AC

Q9HB55 (Hs)

EC number

1.14.14.1

Comment

Fetal expression only and considered an orphan CYP [6]. Testosterone may be a substrate [5].

References

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1. Daly AK. (2006) Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet, 45 (1): 13-31. [PMID:16430309]

2. Fontana E, Dansette PM, Poli SM. (2005) Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab, 6 (5): 413-54. [PMID:16248836]

3. Furster C, Wikvall K. (1999) Identification of CYP3A4 as the major enzyme responsible for 25-hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha-triol in human liver microsomes. Biochim Biophys Acta, 1437 (1): 46-52. [PMID:9931427]

4. Greenblatt DJ, Harmatz JS. (2015) Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies. Br J Clin Pharmacol, 80 (3): 342-50. [PMID:25923589]

5. Groarke DA, Drmota T, Bahia DS, Evans NA, Wilson S, Milligan G. (2001) Analysis of the C-terminal tail of the rat thyrotropin-releasing hormone receptor-1 in interactions and cointernalization with beta-arrestin 1-green fluorescent protein. Mol Pharmacol, 59 (2): 375-85. [PMID:11160875]

6. Guengerich FP, Cheng Q. (2011) Orphans in the human cytochrome P450 superfamily: approaches to discovering functions and relevance in pharmacology. Pharmacol Rev, 63 (3): 684-99. [PMID:21737533]

7. Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, Waxman DJ. (1986) Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem, 261 (11): 5051-60. [PMID:3514607]

8. Kharasch ED, Mitchell D, Coles R, Blanco R. (2008) Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir. Antimicrob Agents Chemother, 52 (5): 1663-9. [PMID:18285471]

9. Sevrioukova IF, Poulos TL. (2015) Current Approaches for Investigating and Predicting Cytochrome P450 3A4-Ligand Interactions. Adv Exp Med Biol, 851: 83-105. [PMID:26002732]

10. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA. (2002) Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos, 30 (8): 883-91. [PMID:12124305]

11. Zhou SF. (2008) Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab, 9 (4): 310-22. [PMID:18473749]

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.