Liver P450 enzymes

A characteristic of the liver P450 enzymes is their almost total lack of substrate specificity, distinguishing them from the adrenal gland enzymes which are much more specific (B-74MI11003). In addition to hydroxylation of hydrocarbons, which involves the conversion of C—H bonds to C—OH bonds and C=C bonds to epoxide rings, a multitude of other types of reaction are catalyzed. These include (V-oxidation, 5-oxidation, N-, S- and O-dealkylation, peroxidation, deamination, desulfuration and dehalogenation, as well as... 

Ethylene, propene, and octene, all linear olefins, only detectably alkylate pyrrole ring D of the prosthetic heme of the phenobarbital-inducible rat liver P450 enzymes (Figure 7.15), but heme alkylation by the more globular olefins 2-isopropyl-4-pentenamide and 2,2-diethyl-4-pentenamide is less regiospecific ... 

Table 9.1. Hormonal Regulation of Sex-Dependent Rat Liver P450 Enzymes...

Mechanisms of testosterone regulation. The mechanisms by which neonatal testosterone imprints the expression of liver P450 enzymes during adulthood are only partially understood. Testosterone s primary effects on liver P450 profiles are mediated by the hypothalamic-pituitary axis and its control of the sex-dependent pattern of pituitary GH secretion -Consistent with this conclusion, testosterone has only minor effects on liver enzyme profiles in hypophysectomized rats in most but not all instances. As discussed in Section 4.2, pituitary GH secretory patterns play a key role in regulating the expression of the sex-dependent P450 forms. 

Uncontrolled insulin-dependent diabetes is accompanied not only by defective carbohydrate metabolism, which results in hyperglycemia, h3q)erlipidemia, and hyperketonemia, but it is also associated with hormonal perturbation, including a reduction in circulating testosterone, thyroid hormone, and plasma Gtf . As described earlier in this chapter, these hormones regulate many liver P450 enzymes, either directly or indirectly. Accordingly, the diabetic state is... 

A a Eh X 0 a e Eh P) t=L Use with caution in patients over 50 years oid with kidney or liver faiiure. PO/IV/IM. Little plasma protein binding, little metabolism. Cimetidine increases serum concentrations of many drugs (oral anticoagulants, theophylline, lidocaine, phenytoin, benzodiazepines, nifedipine, propranolol) by inhibiting liver P450 enzymes. May inhibit renal tubular secretion of procainamide. ... 

Table 11.1 Hormonal regulation of sex- dependent rat liver P450 enzymes ...

A role for estrogen in the expression of the female-specific liver P450 enzymes is suggested by the effects of ovariectomy at birth, which reduces, but does not abolish, hepatic expression of CYP2C7, CYP2C12, and steroid 5a-reductase in adult female rats [26, 65, 69], and by the res-... 

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