UDP-galactosamine

The rapid and extensive depletion of UTP is thought to be the basic cause of the toxicity. Galactosamine combines with UDP to form UDP-galactosamine (Fig. 7.62), which sequesters UDP, and therefore does not allow cycling of uridine nucleotides. Consequently, synthesis of RNA and hence protein are depressed, and sugar and mucopolysaccharide metabolism are disrupted. The latter effects may possibly explain the membrane damage that occurs. The toxic effects of galactosamine can be alleviated by the administration of UTP or its precursors. 

A new chemoenzymatic synthesis of UDP-GalNAc consists of a multi-enzyme catalyzed generation of UDP-galactosamine from uridine-5 monophosphate (UMP) and sucrose in a repetitive batch mode, followed by a chemical acetylation step [164],... 

Uridine-5 -diphosphate galactose (UDP-Gal) Uridine-5 -diphosphate glucosamine (UDP-GlcNAc) 1 Uridine-5 -diphosphate galactosamine (UDP-GalNAc) j 4.5-180 18 2, 3 2... 

The genetic basis for the ABO blood groups is well understood. There are three alleles, variants of a gene, that encodes a glycosyltransferase. In A type individuals, this enzyme transfers N-acetyl-galactosamine from a carrier molecule, called UDP... 

Fig. 14. Salvage pathways of nucleotide sugars. L-fucose (11), (3-L-fucose-l-phosphate (12), GDP-p-L-fucose (13), A fucokinase (EC 2.7.1.52), B GDP-Fuc pyrophosphorylase (EC 2.7.7.30). D-galactose (14), a-D-galactose-l-phosphate (15), UDP-a-D-galactose (16), C galactokinase (EC 2.7.1.6), D UDP-Gal pyrophosphorylase. IV-acetyl-D-galactosamine (17), Al-acetyl-a-D-galactosamine-l-phosphate (18), UDP-lV-acetyl-a-D-galactosamine (19), E IV-acetyl-galactosamine kinase (EC 2.7.1. ), F UDP-GalNAc pyrophosphorylase (EC 2.7.7. )...

Tsuruta O, Shinohara G, Yuasa H et al (1997) UDP-N-acetyl-5-thio-galactosamine is a substrate of lactose synthase. Bioorg Med Chem Lett 7 2523-2526... 

Roth J., Wang Y., Eckhardt A.E. and Hill R.L. (1994). Subcellular localization of the UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase-... 

Wragg S, Hagen FK, Tabak LA. Kinetic analysis of a recom- 22. binant UDP-A-acetyl-D-galactosamine polypeptide A-acetylga-lactosaminyltransferase. J. Biol. Chem. 1995 270(28) 16947-16954. 

A novel human UDP-W-acetyl-D-galactosamine polypeptide A-acetylgalactosaminyltransferase, GalNAc-T7, with specificity... 

Chrungoo, V.X, Reen, R.K., Singh, K., Singh, J. Effects of Silymarin on UDP-glucuronic acid and gjucuronidation activity in the rat isolated hepatocytes and liver in relation to D-galactosamine toxicity. Ind. J. Exp. Biol. 1997 35 256-263... 

Tsuruta, O, Shinohara, G, Yuasa, H, Hashimoto, H, UDP-A-acetyl-5-thio-galactosamine is a substrate of lactose S3mthase, Bioorg. Med. Chem. Lett., 1, 2523-2526, 1997. 

Wandall, H H, Hassan, H, Mirgorodskaya, E, Kristensen, A K, Roepstoiff, P, Bennett, E P, Nielsen, P A, Holhngsworth, M A, Burchell, J, Taylor-Papadimitriou, J, Clausen, H, Substrate specificities of three members of the human UDP-A-acetyl-a-D-galactosamine pol3fpeptide A-acetylgalactosami-nyltransferase family, GalNAc-Tl, -T2, and -T3, J. Biol. Chem., 272, 23503-23514, 1997. 

Galactosamine is one of the hepatotoxicants known to have age-dependent hepatotoxicity (carbon tetrachloride-chlordecone combination, chloroform, and thioacetamide are other examples). It has been reported that neonatal (5 days old) and old rats (24 months old) are less susceptible to galactosamine-induced liver damage as compared to adult rats (5 months old) due to increased liver tissue repair. It is also known that primary hepatocytes isolated from old rats exhibited higher basal levels of UTP, UDP, and UMP in the liver, which may play a role in the... 

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