Reductases

The reductive enzymology of drug metabolism is the most poorly characterized, but perhaps most complex, of the common drug metabolism processes. This is due, in part, to the host of enzyme systems that can catalyze this reaction, including, but not limited to, ADH, aldo-keto reductases (AKR), carbonyl reductases, quinone reductases, P450 reductase, and even P450 itself where conditions of low oxygen tension prevail. Moreover, reductase enzyme activity can be found throughout nature and in a variety of subcellular fractions, although NADPH-dependent cytosolic enzymes generally predominate. Another facet of the complexity of reductase enzymology is the reversible nature of many of the reactions, made possible by the redox behavior of the common nicotinamide cofactors, NADH and NADPH. For example, although ADHs can catalyze the (reductive) bioactivation of chloral hydrate to trichloroethanol by transferring a hydride from NADH to the substrate, the enzyme is more commonly associated with its important dehydrogenase (oxidative) function in the NAD+-dependent metabolism of ethanol to acetaldehyde. A common feature of carbonyl (and quinone) reductases is their two-electron reduction mechanism. In contrast, P450 and P450 reductase catalyze one electron reduction processes often associated with xenobiotic toxicity, but also productively in the bioactivation of some anticancer drugs.

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