Regulation of sialic acid metabolism

Vimr, E. R., and Troy, F. A., 1985b, Regulation of sialic acid metabolism in Escherichia coli Role of N-acyIneuraminate pyruvate-lyase, J. Bacterial. 164 854-860. 

Hormonal regulation is on a short or long term basis. The short term influence of hormones causes changes in intermediate levels which in turn can modify the substrate level control of sialic acid metabolism, either as substrates or effectors. Cellular ratios of e.g. ATP (AMP + ADP) or AcCoA CoA and hexose-monophosphate levels due to insulin, glucagon and glucocorticosteroid action... 

An increased rate of metabolic clearance has been observed after removal of sialic acid from human, low-density lipoprotein in vivo.472 Sialic acid controls the receptor-mediated uptake of this lipoprotein by fibroblasts. Removal of sialic acid residues accelerates the rate of internalization of the lipoprotein and, subsequently, the regulation of the metabolism of cellular cholesterol.473... 

Kontou, M., Bauer, C., Reutter, W., Horstkorte, R. (2008). Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells. Glycoconjug. J., 25, 237-244. 

The biosynthesis of sialic acids begins with D-glucose (Glc), the commoDr precursor of all monosaccharides in complex carbohydrate metabolism. The complete pathway provides both N-acetylhexosamines and sialic acids for biosynthesis and can be divided up into two halves with UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) as the central metabolite. The individual steps are presented in the schemes in Figs. 1 and 2, and a summary of the regulation on the complete pathways is shown in Fig. 9. 

Servomechanisms play important roles in the regulation of several other pathways of mammalian metabolism, including the synthesis of purines (Wyngaarden and Kelley, 1978), pyrimidines (Levine et al., 1974), porphyrins (Meyer and Schmid, 1978), and sialic acids (Komfeld et al., 1964). A detailed discussion of each instance is beyond the scope of this chapter. Some examples of feedback control are cited in Table 1. 

Another, more classical, control mechanism exists for the feedback regulation of key enzymes for the synthesis of Gm-6-P04 and for N-acetylmannosamine. Each of these is the first enzyme in the metabolic commitment to hexosamine and sialic acid synthesis. Komfeld et al, (1964) showed that UDP-GlcNAc is an efficient feedback inhibitor for L-glutamine-D-fructose-6-phosphate aminotransferase and that CMP-NAN also inhibits UDP-GlcNAc-2-epimerase, which is responsible for the synthesis of A/ -acetylmannosamine. This is an example of the by now familar endproduct inhibition of the first enzyme of a metabolic pathway (see Figure 6). They were also able to demonstrate that in vivo administration of puromycin to rats, which inhibits de novo protein synthesis and also depresses sialic acid and hexosamine utilization, does not lead to an accumulation of UDP-GlcNAc. Furthermore, the turnover of the UDP-hexosamine pool was shown to be slowed down. These data suggest that impairment of the utilization of UDP-hexosamine leads to decreased synthesis of UDP-hexosamines or their precursors (i.e., classical feedback inhibition). 

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