Formation of Reactive Metabolites of Foreign Compounds and their Covalent Binding to Cellular Constituents

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Formation of Reactive Metabolites of Foreign Compounds and their Covalent Binding to Cellular Constituents

James R. Gillette

10.1002/cphy.cp090137

Source: Supplement 26: Handbook of Physiology, Reactions to Environmental Agents

Originally published: 1977

Published online: January 2011

Full Article on Wiley Online Library

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Abstract

The sections in this article are:

1 Theoretical Considerations

2 Examples

2.1 Acetaminophen

2.2 Bromobenzene

2.3 Furosemide

2.4 Isoniazid and Iproniazid

3 Conclusion

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James R. Gillette. Formation of Reactive Metabolites of Foreign Compounds and their Covalent Binding to Cellular Constituents. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 577-589. First published in print 1977. doi: 10.1002/cphy.cp090137

	Figure 1. Mechanisms of toxicity.
	Figure 2. Kinetics of covalent binding of reactive metabolites. In this model, k_fo is the first‐order rate constant for the excretion of the unchanged foreign compound into urine, k_fm is the sum of the first‐order rate constants for the conversion of the foreign compound to inactive metabolites (M_f), and k_fp is the first‐order rate constant for the formation of the proximate metabolite. The comparable first‐order rate constants for the proximate metabolite are k_po, k_pm, and k_pr, and the first‐order rate constants for the reactive metabolite are k_ro, k_rm, and k_rc.
	Figure 3. Pathways of acetaminophen metabolism.
	Figure 4. Pathways of bromobenzene metabolism.
	Figure 5. Possible pathway of furosemide metabolism.
	Figure 6. Major pathways of isoniazid metabolism.

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Article Title:	Formation of Reactive Metabolites of Foreign Compounds and their Covalent Binding to Cellular Constituents
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