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Review
. 2015 Jan 20;28(1):38-42.
doi: 10.1021/tx500444e. Epub 2014 Dec 19.

Survey of Human Oxidoreductases and Cytochrome P450 Enzymes Involved in the Metabolism of Xenobiotic and Natural Chemicals

Slobodan Rendic  1 , F Peter Guengerich  2
Affiliations
Review

Survey of Human Oxidoreductases and Cytochrome P450 Enzymes Involved in the Metabolism of Xenobiotic and Natural Chemicals

Slobodan Rendic et al. Chem Res Toxicol. .

Abstract

Analyzing the literature resources used in our previous reports, we calculated the fractions of the oxidoreductase enzymes FMO (microsomal flavin-containing monooxygenase), AKR (aldo-keto reductase), MAO (monoamine oxidase), and cytochrome P450 participating in metabolic reactions. The calculations show that the fractions of P450s involved in the metabolism of all chemicals (general chemicals, natural, and physiological compounds, and drugs) are rather consistent in the findings that >90% of enzymatic reactions are catalyzed by P450s. Regarding drug metabolism, three-fourths of the human P450 reactions can be accounted for by a set of five P450s: 1A2, 2C9, 2C19, 2D6, and 3A4, and the largest fraction of the P450 reactions is catalyzed by P450 3A enzymes. P450 3A4 participation in metabolic reactions of drugs varied from 13% for general chemicals to 27% for drugs.

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Figures

Figure 1
Figure 1
(A) Human oxidoreductases participating in the metabolism of all chemicals. n = 8320 reactions; 1829 compounds used in calculations. (B) Human P450s participating in the metabolism of all chemicals (drugs, physiological compounds, and general chemicals), n = 7906 data reactions; 1829 compounds used in calculations.
Figure 2
Figure 2
(A) Human oxidoreductases participating in metabolism of general chemicals. n = 2437 reactions; 638 compounds used in calculations. (B) Human P450s participating in metabolism of general chemicals. n = 2248 reactions; 638 compounds used in calculations.
Figure 3
Figure 3
(A) Human oxidoreductases participating in the metabolism of drugs (calculation for drugs under development and marketed drugs). n = 4192 reactions; 860 drugs used in calculations. (B) Human P450 enzymes in the metabolism of drugs (data calculated for minor and major reactions, drugs under development, and marketed drugs). n = 4058 reactions; 860 drugs used in calculations.
Figure 4
Figure 4
(A) Human oxidoreductases participating in the metabolism of natural and physiological compounds. n = 1693 reactions; 331 compounds used in calculations. (B) Human P450s participating in the metabolism of natural/physiological compounds. n = 1601 reactions; 331 compounds used in calculations.
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References

    1. Rendic S.; Guengerich F. P. (2012) Contributions of human enzymes in carcinogen metabolism. Chem. Res. Toxicol. 25, 1316–1383. - PMC - PubMed
    1. Rendic S. (2002) Summary of information on human CYP enzymes: Human P450 metabolism data. Drug Metab. Rev. 34, 83–448. - PubMed
    1. Rendic S.; Di Carlo F. J. (1997) Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29, 413–580. - PubMed
    1. ADME Database: WEB Searchable ADME Database of Substrates, Inhibitors, Inducers and Activators of Cytochrome P450, Other Enzymes and Drug Transporters, Fujitsu Kyushu System Ltd., Fukuoka, Japan, http://jp.fujitsu.com/group/kyushu/en/services/admedatabase/.
    1. Williams J. A.; Hyland R.; Jones B. C.; Smith D. A.; Hurst S.; Goosen T. C.; Peterkin V.; Koup J. R.; Ball S. E. (2004) Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab. Dispos. 32, 1201–1208. - PubMed

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