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Microsomal Enzyme: Comparison
Please note this is a comparison between Version 1 by Yu Peng and Version 2 by Yu Peng.

Microsomal enzymes are the drug-metabolizing enzymes that remain associated with fragments of the smooth endoplasmic reticulum after liver tissue is homogenized and subjected to differential centrifugation, yielding a membrane-bound vesicle fraction termed microsomes [1]. The microsomal drug-metabolizing system of the liver consists of two protein components—cytochrome P450 and NADPH-cytochrome c reductase—together with the lipid phosphatidylcholine; cytochrome P450 serves as the binding site for oxygen and substrate, the reductase shuttles electrons from NADPH to cytochrome P450, and the phospholipid facilitates electron transfer between them [2]. This system is classified as a mixed-function oxidase or monooxygenase: it requires both NADPH and molecular oxygen, and it incorporates one atom of oxygen into the substrate while reducing the second oxygen atom to water [3]. Microsomal enzymes occupy the principal position in phase I xenobiotic biotransformation, catalyzing aromatic and aliphatic hydroxylation, N-, O-, and S-dealkylation, deamination, dehalogenation, sulfoxidation, N-oxidation, and azo- and nitro-reduction [2][3]. Within the taxonomy of pharmacogenetics and drug metabolism, the term designates this membrane-associated, cytochrome P450–centered enzyme system as the object of studies on substrate specificity, enzyme induction, competitive and mechanism-based inhibition, and interindividual variability in hepatic drug clearance [3]. The microsomal fraction also retains phase II enzymes situated in the endoplasmic reticulum, notably UDP-glucuronosyltransferases, whose activity is influenced by the membrane environment in which the microsomal preparation embeds them [4].

  • Cytochrome P450
  • mixed-function oxidase
  • phase I metabolism
  • human liver microsomes

Pharmacogenetics and Drug Metabolism·Pharmacology·Pharmacology, Toxicology and Pharmaceutics·Life Sciences

References

  1. C. Ioannides; D. V. Parke; The Cytochrome P450 I Gene Family of Microsomal Hemoproteins and Their Role in the Metabolic Activation of Chemicals. Drug Metab. Rev. 1990, 22, 1-85. [CrossRef]
  2. Sharon K. Krueger; David E. Williams; Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol. Ther. 2005, 106, 357-387. [CrossRef]
  3. Palrasu Manikandan; Siddavaram Nagini; Cytochrome P450 Structure, Function and Clinical Significance: A Review. Curr. Drug Targets 2018, 19, 38-54. [CrossRef]
  4. Yuejian Liu; Michael W. H. Coughtrie; Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?. Pharmaceutics 2017, 9, 32. [CrossRef]
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