Nutrient-CYP Action: Mechanism for drug-nutrient interactions
Nutrient |
Action |
Enzyme |
Reference |
Vitamin A (Retinol & RA) |
Substrate |
CES 1, CYP 1A1, 2B6, 2C19, UGT 287 |
1,2,3,4,5 |
Inhibitor |
CES 1, CYP 2C8 |
||
Inducer |
CYP 1A1 |
||
|
|
|
|
Vitamin C |
Inducer |
CYP 3A4 |
6 |
|
|
|
|
Vitamin D (Cholecalciferol) |
Substrate |
CYP450, 1A1, 2C19, 2J2, 2R1, |
1,3,4,7-19 |
Inhibitor |
CYP450, 1A1, 2B6, 2C19, 2C9, 2D6, 2J2, 3A4, 11A1, 27A1 |
||
|
|
|
|
Vitamin E (Tocopherol) |
Transporter |
MRP 1 |
20 |
|
|
||
|
|
|
|
Thiamin |
Inducer |
CYP 4B1 |
21 |
|
|
|
|
Vitamin B3 (Niacinamide) |
Inhibitor |
CYP 2D6, 2E1, 3A4 |
3, 22 |
Substrate |
CYP 3A4 |
||
|
|
|
|
Vitamin B6 (Pyridoxine) |
Inhibitor |
CYP 1A1 |
23 |
|
|
|
|
|
|
|
|
Biotin |
Inducer |
CYP 1B1 |
3 |
|
|
|
|
SelenoCysteine Conjugates |
Inhibitor |
CYP 1A1, 1A2, 2C19, 2C9, 2D6, 2E1, 3A4 |
24 |
|
|
||
|
|
|
|
Zinc 2+ |
Inhibitor |
CYP 3A4 |
25 |
|
|
|
|
Copper 2+ |
Inhibitor |
CYP 1A1, 3A4 |
26 |
|
|
|
|
Ginkgo Biloba |
Inhibitor |
CYP 1A2, 3A4 |
27 |
1. Retinyl ester hydrolase: https://www.uniprot.org/uniprot/P23141
2. Schreiber R, Taschler U, Preiss-Landl K, Wongsiriroj N, Zimmermann R, Lass A. Retinyl ester hydrolases and their roles in vitamin A homeostasis. Biochim Biophys Acta. 201 Jan;1821(1):113-23.
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6. van Heeswijk RP, Cooper CL, Foster BC, Chauhan BM, Shirazi F, Seguin I, Phillips EJ, Mills E. Effect of high-dose vitamin C on hepatic cytochrome P450 3A4 activity. Pharmacotherapy. 2005 Dec;25(12):1725-8.
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9. Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7.
10. Ohyama Y, Yamasaki T: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci. 2004 Sep 1;9:3007-18.
11. Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K, Yamada S, Terato H, Ide H, Ohyama Y: Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56. Epub 2006 Jul 13.
12. Gupta RP, He YA, Patrick KS, Halpert JR, Bell NH. CYP3A4 is a vitamin D-24- and 25-hydroxylase: analysis of structure function by site-directed mutagenesis. J Clin Endocrinol Metab. 2005 Feb;90(2):1210-9.
13. Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, Slominski A: Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):213-9.
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15. Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW: A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14754-9.
16. Lehmann B, Tiebel O, Meurer M: Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents--a preliminary study. Arch Dermatol Res. 1999 Sep;291(9):507-10.
17. Sawada N, Sakaki T, Yoneda S, Kusudo T, Shinkyo R, Ohta M, Inouye K: Conversion of vitamin D3 to 1alpha,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem Biophys Res Commun. 2004 Jul 16;320(1):156-64.
18. Sakaki T, Kagawa N, Yamamoto K, Inouye K: Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. Print 2005 Jan 1.
19. Ohyama Y, Yamasaki T: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci. 2004 Sep 1;9:3007-18.
20. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43.
21. Liu S, Stromberg A, Tai HH, Moscow JA: Thiamine transporter gene expression and exogenous thiamine modulate the expression of genes involved in drug and prostaglandin metabolism in breast cancer cells. Mol Cancer Res. 2004 Aug;2(8):477-87.
22. Gaudineau C, Auclair K. Inhibition of human P450 enzymes by nicotinic acid and nicotinamide. Biochem Biophys Res Commun. 2004 May 7;317(3):950-6.
23. Tangjarukij C, Navasumrit P, Zelikoff JT, Ruchirawat M: The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B6C3F1 mice. J Immunotoxicol. 2009 Sep;6(3):147-60.
24. Kim JS, Yun CH. Inhibition of human cytochrome P450 3A4 activity by zinc(II) ion. Toxicol Lett. 2005 Apr 28;156(3):341-50. Epub 2005 Jan 11.
25. Kim JS, Ahn T, Yim SK, Yun CH. Differential effect of copper (II) on the cytochrome P450 enzymes and NADPH-cytochrome P450 reductase: inhibition of cytochrome P450-catalyzed reactions by copper (II) ion. Biochemistry. 2002 Jul 30;41(30):9438-47.
26. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med. 2005 Jun;11(3):433-9.