Drug metabolism amino acid conjugation

AJ Hutt,J Caldwell. Amino Acid Conjugation. In GJ Mulder, ed. Conjugation Reactions in Drug Metabolism An Integrated Approach. London Taylor Francis, 1990, pp 273—306. 

Conjugations. Conjugation reactions are Phase II metabolic reactions that are enzymatically catalyzed and involve the attachment of small polar molecules (glucuronic acid, sulphate, amino acids) to the drug. This, in turn, makes the drug more water soluble and... 

Drug metabolism occurs primarily in the liver and most commonly involves oxidation, reduction, hydrolysis, and conjugation reactions. Quantitatively, the most important hepatic enzymes are the cytochrome P450 enzymes that have been divided into families and subfamilies (e.g., CYP3A4) based on the similarity of their amino acid sequences. These enzymes are responsible for the metabolism of a large number of drugs. 

ABSORPTION, METABOLISM, AND EXCRETION When administered oraUy, methyldopa is absorbed by an active amino acid transporter. Peak plasma concentrations occur after 2-3 hours. The drug is eliminated with a of 2 hours (prolonged to 4-6 hours in patients with renal failure). Methyldopa transport into the CNS apparently is an active process. Methyldopa is excreted in the urine primarily as the sulfate conjugate (50-70%) and as the parent drug (25%). The remainder is excreted as other metabolites, including methyldopamine, methylnorepinephrine, and O-methylated products of these catecholamines. 

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