Drug-metabolizing enzymes, function

Sheweita, S.A. (2000) Drug-metabolizing enzymes mechanisms and functions. Current Drug Metabolism, 1, 107-132. 

Ghersi-Egea JF Minn A, Siest G (1988) A new aspect of the protective functions of the blood-brain barrier Activities of four drug-metabolizing enzymes in isolated brain microvessels. Life Sci 42 2515-2523... 

Passive transcellular transport across the intestinal epithelium involves three discrete steps (1) uptake across the apical membrane, (2) diffusion through the cytoplasm, and (3) efflux across the basolateral membrane. Occasionally, drug molecules without favorable physicochemical properties traverse the intestinal epithelium using endogenous membrane transporters.6-8 In addition, the intestinal mucosa, with its numerous drug-metabolizing enzymes and efflux transporters, such as P-glycoprotein (Pgp), functions as a biochemical barrier.9... 

Most phase one reactions are catalyzed by the drug-metabolizing enzymes (mixed function oxidases, oxygenases) located in the endoplasmic reticulum of liver and, to a lesser extent, in intestine, kidney, and lung. These enzymes have been the subject of intensive research (G7, G8, LI). 

It must be recognized that developmental differences in hepatic drug metabolism occur consequent to reductions in the activity of specific drug-metabolizing enzymes and their respective isoforms. For most enzymes, the greatest reduction of activity is seen in premature infants where immature function may also reflect continued organogenesis. This... 

Unlike renal function, hepatic maturation is generally believed to be a two-stage process with the major development completed at 4 weeks postpartum and tlie second stage completed by about 10 weeks of age. In sheep, for example, tlie activity of a number of hepatic drug-metabolizing enzymes was found to be relatively low in animals aged up to 6 months compared with adult individuals... 

Y. Shitara, Y. Sugiyama, Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions, Pharm. Ther. 112 (2006) 71-105. 

---