A. Amino sugar synthesis
Amino sugars are essential components of glycoconjugates such as proteoglycans, glycoproteins, and glycolipids. The synthetic pathway of amino sugars (hexosamines) is very active in connective tissues, where as much as 20% of glucose flows through this pathway.
1. N-Acetylglucosamine and N-acetylgalactosamine: The monosaccharide fructose 6-phosphate is the precursor of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc). A hydroxyl group on the fructose is replaced by the amide nitrogen of a glutamine, and the glucosamine 6phosphate product gets acetylated, isomerized, and activated, producing the nucleotide sugar UDP-GlcNAc (Fig. 14.8). UDP-GalNAc is generated by the epimerization of UDP-GlcNAc. It is these nucleotide sugar forms of the amino sugars that are used to elongate the carbohydrate chains.
pyrophosphate.
2. N-Acetylneuraminic acid: NANA, a nine-carbon, acidic monosaccharide (see Fig. 17.15, p. 209), is a member of the family of sialic acids, each of which is acylated at a different site. These compounds are usually found as terminal carbohydrate residues of oligosaccharide side chains of glycoproteins, of glycolipids, or, less frequently, of GAG. N-Acetylmannosamine 6-phosphate (derived from fructose 6-phosphate) and phosphoenolpyruvate (an intermediate in glycolysis; see p. 102) are the immediate sources of the carbons and nitrogens for NANA synthesis (see Fig. 14.8). Before NANA can be added to a growing oligosaccharide, it must be activated to cytidine monophosphate (CMP)NANA by reacting with cytidine triphosphate (CTP). CMP-NANA synthetase catalyzes the reaction. [Note: CMP-NANA is the only nucleotide sugar in human metabolism in which the carrier nucleotide is a monophosphate rather than a diphosphate.]
B. Acidic sugar synthesis
D-Glucuronic acid, whose structure is that of glucose with an oxidized carbon 6 (−CH2OH → −COOH), and its C-5 epimer, L-iduronic acid, are essential components of GAG. Glucuronic acid is also required for the detoxification of lipophilic compounds, such as bilirubin (see p. 282), steroids (see p. 240), and many drugs, including the statins (see p. 224), because conjugation with glucuronate (glucuronidation) increases water solubility. In plants and mammals (other than guinea pigs and primates, including humans), glucuronic acid is a precursor of ascorbic acid (vitamin
C) as shown in Figure 14.9. This uronic acid pathway also provides a mechanism by which dietary D-xylulose can enter the central metabolic pathways.