Phase I metabolism enzymes

Toluene alone is not a severe immunotoxin. When administered in combination with benzene, a potent immunotoxin, toluene enhances the immunotoxic effects of benzene. It does so by competing with benzene for Phase I metabolizing enzymes, thereby allowing benzene concentrations in the body to remain higher than if benzene were present alone. I23l... 

The catalysis leading to the active principle is hydrolytic (either through general catalysis or through extra-hepatic enzymes) for carrier prodrugs. For bioprecursors, it seems largely restricted to Phase I metabolizing enzymes. 

As inhibitors of certain enzyme reactions and apoptosis related to the development of cancer (Naasani et al, 1998 Yang et al, 2001), specifically by selective induction or modification of phase I and phase II metabolic enzymes so as to increase the formation and excretion of detoxified metabolites of carcinogens. 

Virtually all organisms possess biotransformation or detoxification enzymes that convert lipophilic xenobiotics to water-soluble and excretable metabolites (Yu et al. 1995). In the metabolic process, PAHs are altered by Phase I metabolism into various products such as epoxides, phenols,... 

With respect to drug-metabolizing enzymes, the majority of the CYPs responsible for phase I metabolism are concentrated in liver. The CYPs considered here are all found in the endoplasmic reticulum (isolated as microsomes ). Of the 18 human CYP families known, the bulk of xenobiotic biotransformation processes are carried out by enzymes from the CYP1, CYP2 and CYP3 families. In humans, realistically,... 

Table 11.3 Summary of the Expression Pattern and Activities of Phase I and Phase II Metabolic Enzymes and Various Peptidases/Proteases in Human Peripheral Lung Tissues, Primary Rat AEC Culture and Human Alveolar Epithelial Cell Line, A549.

Age-related changes in phase I metabolism coupled with the use of multiple medications place older patients at increased risk for adverse drug reactions. Adverse drug reactions occur due to either inhibition or induction of CYP enzymes, especially CYP3A, which is believed to be involved in the metabolism of more than one half of the currently prescribed drugs.Clinical outcomes are determined by... 

Phase I metabolic reactions involve oxidation, reduction, or hydrolysis of the parent molecule, resulting in the formation of a more polar compound. Phase 1 reactions are mediated by the cytochrome P450 (GYP) family of enzymes. While metabolism used to be thought of as the body s detoxification process, phase I metabolites may be equally or even more pharmacologically active than the parent compound. Drug metabolism in general, and CYP-based mechanisms in particular, are discussed in detail in Chapter 5. 

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