Hexosamine metabolism

Fig. 1. Mammalian hexosamine metabolism. The de novo biosynthesis of UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) from D-glucose (Glc) is shown...

Winterbum and Phelps (1970) have suggested that the L-glutamine-D-fructose-6-phosphate aminotransferase does not display classical feedback kinetic behavior in the presence of UDP-GlcNAc. Furthermore, they suggest that there is a 10-fold excess of enzyme over that necessary for a steady state for hexosamine metabolism. 

Radioactive acetate is a cheaper, readily available precursor for experiments on the labelling of sialic acid in tissues or cells, and it effectively labels the N- and O-acyl groups of sialic acids.228 This method is of great value not only for the preparation of radioactive sialic acids having high specific radioactivity but also for metabolic studies of sialic acids. However, the sialic acids must be isolated before determination of the specific radioactivity, as other aeetylated hexosamines are also labelled. 

Kazel K. and Domenjoz R. 1971. Effects of hexosamine derivatives and uronic acid derivatives on gjycosamin-oglycan metabolism of fibroblast cultures. Pharmacology 5 337-345. 

Acetyl CoA can be converted to fatty acyl CoA by one of two routes. One utilises 3-hydroxyacyl CoA dehydrogenase and the other, which proceeds via malonyl CoA, uses acetyl CoA carboxylase. The former route is considered to be reversible and 3-hydroxyacyl CoA dehydrogenase is therefore an enzyme of fatty acid oxidation also. When formed, fatty acyl CoA can be incorporated into other lipids as shown in Figure 2.11. Palmityl CoA, however, has other important utilisation routes leading to the synthesis of sphingomyelins (phospholipid) or ceramide hexosides. The latter represent an important junction of lipid and hexose metabolism and are precursors of the gangliosides which contain hexose, hexosamine, and A -acetylneuraminic acid (referred to briefly under glycolipid synthesis above). 

Gin is therefore a central intermediate in nitrogen metabolism, providing (by transamidation) the amide nitrogen required in the synthesis of a variety of other compounds (Fig ). It also plays an important role in the kidney, where it is hydrolysed to provide free ammonia, which aids resorption of potassium and sodium ions. Gin is an important nutrient for the brain (see Glutamic acid). Because its amide group is involved in the biosynthesis of hexosamines. Gin promotes the regeneration of mucoproteins and the intestinal epithelium. 

Aminosugars are of extraordinary biological importance in nature. Usually, they are found in the M-acetylated form or as sulfates and not as free bases. The corresponding aminopolysaccharides serve as scaffold substances and intercellular adhesives. Furthermore, they play an important role in the metabolism and are connected with the pathology of many diseases. Hexosamines are constituents of blood group determinants, partial structures of antibiotics, components... 

The widespread distribution of D-giucosamine (I) and n-galactosamine (II) is presumably due to the closeness of the metabolic relationship between these hexosamines (Davidson, 1966) and the ubiquitous, and thermodynamically most stable hexose, n-glucose. While it is possible that some of the other hexosamine structures listed in Table I have yet to be detected as natural components in materials of animal origin, it is unlikely that such sources would match the diversity of hexosamine structures exhibited in compounds from microoi anisms. 

In Table VI are estimates of the metabolic turnover rates of some hexosamine-containing glyeolipids, glycosaminoglycans, and glycoproteins in mammalian systems. While not all the materials listed there behave as single metabolic pools, certain of these results have been interpreted as evidence that component hexosamines are metabolized simultaneously with the associated protein, and the A -acetyl and 0-sulfate residues (Schiller et of., 1656 Gross et al., 1660). 

The fairly convincing evidence (Sandhoff, 1969 Okada and O Brien, 1969 Sandhoff el al., 1968) that in the fatal disorder knowm as Tay-Sachs disease there is a defect in j3-. -acetyI-i)-hexosamiiiidase activity and that this probably leads to the accumulation of hexosamine-containing materials in the tissues should dispel any remaining doubt as to w hether the enzyme has an important jjart to play in normal metabolic processes. This... 

In each of these areas, the anabolism of sialic acid will be emphasized. However, it will also be necessary to discuss the metabolism of other sugars (e.g., hexosamines) in order to place these discussions into an overall biochemical context. 

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