Galactose, biosynthesis metabolism

Optimizing Gaiactosylation of Recombinant Proteins by Metabolically Engineering Galactose Biosynthesis... 

Overexpression of selected enzymes involved in galactose biosynthesis, either independently or collectively as an entire metabolic pathway, may be a route to increased levels of galactosylation in CHO cells. These include the UDP-glucose-4-epimerase [36], the phosphoglucomutase [43], and the UDP-glucose pyrophosphor-ylase [44] and the UDP-galactose transferase [45]. All of the genes for these enzymes have been isolated from either mammalian or microbial sources. 

Understand the mechanisms for /V-acetylglucosamine biosynthesis and degradation of fructose and galactose, and inborn errors of metabolism associated with these pathways Appreciate the physiologic role of the glucuronate pathway and the inborn errors of metabolism associated with its malfunction ... 

The problem of the D-galactose-D-glucose interconversion was discussed on p. 176 in connection with the biosynthesis of lactose, although, in fact, the mechanism was largely elucidated by studying the metabolism of D-galactose in j/eas[Pg.179]

This reaction is important in glycogen biosynthesis and galactose metabolism. The enzyme is composed of two polypeptide chains, labelled A and B. 

See also UDP-Galactose 4-Epimerase, UTP, Glucose-l-Phosphate, Biosynthesis of Glycoconjugates, De Novo Pyrimidine Nucleotide Metabolism, Biosynthesis of Glycoconjugates... 

Sucrase (also called saccharase and invertase) hydrolyzes sucrose. In contrast to the abundant information available on the yeast invertase, little is known of the mammalian sucrases. The significance of invertase and lactase in absorption is illustrated by inborn errors of metabolism in which these two enzymes are absent in the intestinal secretion. (The fact that lactase deficiency does not interfere with growth indicates that the galactose needed for biosynthesis of brain lipids or lens proteins can be synthesized endogenously in amounts sufficient to fulfill the metabolic requirements.) In that case, there is an intolerance to lactose or sucrose with no increase in blood glucose levels or without an increase in the levels of disaccharides... 

In summary, incomplete sialylation of proteins may be the result of inadequate galactosylation and not just from deficiencies of sialic acid biosynthesis. Ultimately, engineering a metabolic net [7] of several enzymes to elevate both sialic acid and galactose levels may be necessary to prepare a universal production host cell capable of giving complete extension of the oligosaccharide side chains for a variety of recombinant glycoproteins under high productivity conditions with robust protein synthesis. 

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