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One example is the N-glucuronidation of an aromatic amine, 4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver. [ 2 ] The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water - soluble than the non-glucuronic acid-containing substances from which they were ...
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug ...
After phase II reactions, the xenobiotic conjugates may be further metabolised. A common example is the processing of glutathione conjugates to acetylcysteine (mercapturic acid) conjugates. [7] Here, the γ-glutamate and glycine residues in the glutathione molecule are removed by Gamma-glutamyl transpeptidase and dipeptidases.
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First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
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Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most ...
This synthesis can be divided into two main phases: The first phase is the synthesis of the trioses, dihydroxyacetone (DHAP) and glyceraldehyde; the second phase is the subsequent metabolism of these trioses either in the gluconeogenic pathway for glycogen replenishment and/or the complete metabolism in the fructolytic pathway to pyruvate ...