Glucuronic acid metabolism

The status of pathological mucopolysaccharides in amyloid, hyalin, granulation tissue, etc., in relation to D-glucuronic acid metabolism, is beyond the scope of this review. Likewise, the endocrine influence on myxedema fluid, the cock s comb, the sex skin of lower primates, chorionic tissue, etc., cannot be discussed here. 

D-Apiose (31) is synthesized from D-glucuronic acid metabolism in a reaction that involves loss of the carboxyl group and C-3 of D-glucuronic acid. The enzyme which requires NAD" has been isolated (Grisebach, 1980). 

In other species ascorbic acid is not a vitamin, but is an intermediate in glucuronic acid catabolism, and its rate of synthesis bears no relation to physiological requirements for ascorbate. Species for which ascorbate is a vitamin lack the enzyme gulonolactone oxidase (EC 1.11.3.8) and have an alternative pathway for glucuronic acid metabolism. 

Fig. 16.6 Glucuronic acid metabolism in man showing the position of the proposed defect in o-glucaric aciduria and the relationship to the known defect in benign pentosuria.

Uronic acids are biosynthetic intermediates m various metabolic processes ascorbic acid (vitamin C) for example is biosynthesized by way of glucuronic acid Many metabolic waste products are excreted m the urine as their glucuronate salts... 

Phase II metabolism The reaction of a phase I metabolite with an endogenous compound, e.g. glucuronic acid, to form a polar compound that is eliminated from the body. 

Xenobiotics are metabolized in two phases. The major reaction of phase 1 is hydroxylation catalyzed by a variety of monooxygenases, also known as the cytochrome P450s. In phase 2, the hydroxylated species are conjugated with a variety of hydrophihc compounds such as glucuronic acid, sulfate, or glutathione. The combined operation of these two phases renders lipophilic compounds into water-soluble compounds that can be ehminated from the body. 

Isomers of D-apiofuranosyl 1-phosphate have been prepared by treating a mixture of jS-o-apio-D-furanosyl and /3-D-apio-L-furanosyl tetra-acetates with crystalline phosphoric acid. a-o-Apio-o- (59) and a-o-apio-L-furanosyl-1-phosphate (60) and their cyclic phosphates were separated by chromatography and identified by H n.m.r. o-Apiose is metabolized in parsley and Lemna minor with the possible formation of UDP-D-apiose. L. minor will convert UDP-a-glucuronic acid into a-o-apio-D-furanosyl-1,2-cyclic phosphate (61) but no evidence of UDP-o-apiose was found, although it is possible that (61) arose from the rapid hydrolysis of UDP-o-apiose. 

Finally, the fact that anthocyanins can reach the brain represents a beginning of an explanation of the purported neuroprotection effects of anthocyanins. Anthocyanins may be eliminated via urinary and biliary excretion routes. " The extent of elimination of anthocyanins via urine is usually very low (< 0.2% intake) in rats and in humans, indicating either a more pronounced elimination via the bile route or extensive metabolism. As mentioned earlier, in the colon, non-absorbed or biliary excreted anthocyanins can be metabolized by the intestinal microflora into simpler break-down compounds such as phenolic acids that may be (re)absorbed and conjugated with glycine, glucuronic acid, or sulfate and also exhibit some biological... 

Hepatic metabolism No Yes oxidation and hydroxylation induces liver enzymes to increase its metabolism and other drugs Yes oxidation and conjugation Yes oxidation and glucuronide conjugation Yes glucuronic acid conjugation Induces its own metabolism in normal volunteers... 

UDP-glucuronyltransferases catalyze the addition of glucuronic acid onto phenol, hydroxyl and carboxylic acid functions of molecules. They are expressed in many tissues of the body, including the liver and intestine [2-5], Microsomes from human intestines have been shown to metabolize UDP-glucuronyltransferase substrates including p-nitrophenol [6], 1-naphthol, morphine, and ethinylestradiol [4]. The relative rates of metabolism of these substrates in liver and intestinal microsomes are shown in Table 13.1. 

Aromatic amines are initially metabolized by aromatic and A -hydroxylation (oxidation reactions) and Y-acetylation. Following aromatic ring hydroxylation, the ring structure may be further conjugated with glucuronic acid or sulfate (Parkinson 1996). N-hydroxylation results in the potential methemoglobin-generating metabolite,... 

Many investigations of relevant enzymes in transformation of xenobiotics by aquatic species have shown that the similar enzymes observed in metabolism in soil, plant, and mammals play a role, such as esterases and oxidases [10, 159, 160]. Metabolism of pyrethroids has been most extensively studied in fish for cypermethrin (5) and permethrin (15). Aromatic hydroxylation at the 4 -position of the 3-phenoxybenzyl moiety followed by conjugation with glucuronic acid... 

Formation of. glucuronide conjugates is a major metabolic conversion for many lipid-soluble compounds. The product glucuronides are more water soluble and usually more readily excreted. The glucuronic acid donor in this reaction is... 

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