Drug biotransformation hormones

A deficiency or surfeit of certain hormones can influence the activity of the enzymes involved in drug biotransformation. Apart from the sex hormones, those of the adrenal, pancreas, pituitary, and thyroid also exert effects on the regulation of certain enzyme activities. Some hormonal disease states, such as diabetes and hyperthyroidism, could have important implications for drug biotransformation. Alterations in drug biotransformation can occur in pregnancy, and this subject area requires much more study. 

The biotransformation of certain drugs may differ in males and females. Such sex differences are fairly common in the rat, which is probably the most widely utilized laboratory animal in drug safety evaluation, but have been infrequently reported for humans or even for other laboratory animal species. When encountered, these sex differences appear to arise as a result of the regulation of drug biotransformation by hormones such as growth hormone. 

Biotransformation. Steroid hormones and bilirubin, as well as drugs, ethanol, and other xenobiotics are taken up by the liver and inactivated and converted into highly polar metabolites by conversion reactions (see p. 316). 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

MT family of enzymes catalyzes the O-, S-, or N-methylation of drugs, hormones, and neurotransmitters, and utilizes S-adenosyl-L-methionine (SAM) as a methyl donor. Catechol-O-methyltransferase (COMT) is the most extensively investigated drug-metabolizing MT. It plays an important role in the biotransformation of both endogenous and exogenous catechols. COMT has a rather broad substrate specificity for structures that contain catechol moieties and is often involved in the methylation of... 

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