Galactose is an important component of our diet, because it is one of the sugars in the milk disaccharide, lactose. The pathway of galactose metabolism and its conversion to glucose is fairly complex (see Fig. 25.6). Galactose is first phosphorylated by a specific hepatic kinase, galactokinase, to form galactose-1-phosphate (Gal-1-P). The conversion of Gal-1-P to Glc-1-P involves the nucleoside diphosphate sugar intermediate, UDP-Glc. The enzyme Gal-1-P uridyl transferase catalyzes an exchange between UDP-Glc and Gal-1-P to form UDP-Gal and Glc-1-P - that is, the Glc-1-P part of UDP-Glc is replaced with Gal-1-P, to give UDP-Gal and Glc-1-P. This enzyme is absent in individuals with galactosemia (see box).
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| The Glc-1-P arising from galactose metabolism can be converted to Glc-6-P by phosphoglucomutase, and thus enter glycolysis. UDP-Glc is present at only micromolar concentrations in cells, so that its availability for galactose metabolism would be quickly exhausted were it not for the presence of UDP-Gal 4-epimerase. This enzyme catalyzes the equilibrium between UDP-Glc and UDP-Gal, providing a constant source of UDP-Glc during galactose metabolism. UDP-Gal 4-epimerase is actually a dehydrogenase, a redox enzyme, requiring NAD+ as a coenzyme. In this reaction, UDP-Gal is first oxidized to the achiral intermediate, UDP-4-ketogalactose, with the reduction of NAD+ to NADH. The 4-keto intermediate is then reduced by the enzyme-bound NADH, but with a change in the stereochemistry of the 4-hydroxyl group, producing UDP-Glc and regenerating NAD+.
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