Glucuronate metabolism

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. 

Glucuronate is reduced to L-gulonate in an NADPH-dependent reaction L-gulonate is the direct precursor of ascorbate in those animals capable of synthesizing this vitamin. In humans and other primates as well as guinea pigs, ascorbic acid cannot be synthesized because of the absence of L-g ulonolactone oxidase. L-Gulonate is metabolized ultimately to D-xylulose 5-phosphate, a constituent of the pentose phosphate pathway. 

Bilirubin formed in peripheral tissues is transported to the hver by plasma albumin. The further metabolism of bihtubin occuts primarily in the hver. It can be divided into thtee processes (1) uptake of bilirubin by hver parenchymal cells, (2) conjugation of bilirubin with glucuronate in the endoplasmic reticulum, and (3) secretion of conjugated bilirubin into the bile. Each of these processes will be considered separately. 

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... 

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

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