UDP-Galactose epimerase

Elevated in deficiencies of galactokinase, galactose-1-phosphate uridyltransferase (classical galactosemia), UDP galactose-4-epimerase, and Fanconi-Bickel-syn drome, portocaval shunt, and cirrhosis, depending on time after lactose consumption. 

Levels of galactose-1-phosphate are elevated to above 100 mg/100 ml RBC in untreated galactose-1-phosphate uridyltransferase deficiency (classical galactosemia) and, to a lesser degree, in UDP galactose-4-epimerase deficiency. 

UDP-galactose-4-epimerase is deficient in epimerase deficiency (MIM 230 350). This disorder is caused by the impaired pathway step from UDP-galactose to UDP-glucose. 

Mutant strains deficient in UDP-galactose-4-epimerase activity are essentially without activity for TDP-galactose. 

Cultures induced for UDP-galactose-4-epimerase display the same ratio of activity increase when TDP-galactose is used as a substrate. 

Figure 8. Reactions catalyzed by E. coli UDP-galactose 4-epimerase...

Table II. Summary of Isotope Effect Data for TDPG-Oxidoreductase and UDP Galactose-4-Epimerase (40)°...

Several independent lines of experimental evidence have been given (41, 42) to substantiate the proposed reaction mechanism for UDP-galactose-4-epimerase, shown in Figure 9. Recently, Kalckar and coworkers (42) used TDP-glucose-4T as a substrate. The initial attack occurs at carbon 4 and results in conversion to the enzyme-bound-4-ulose intermediate, accompanied by formation of enzyme-NADT. The 4-ulose intermediate serves as hydrogen acceptor to restore enzyme-NAD+ and to release product. 

When this mechanism is compared with the one for TDPG-oxido reductase (Figure 2), several similarities are apparent. The axial hydrogen at carbon 4 is the initial point of attack which leads to the enzyme bound 4-ulose intermediate. Release of product from the enzyme occurs only after reoxidation of enzyme-NADH to enzyme-NAD+. A summary of available data to further substantiate our comparative study of TDPG-oxido reductase and UDP-galactose-4-epimerase is given in Table III. 

Table III. Comparison of TDPG-Oxidoreductase (28, 30, 31, 32) and UDP-Galactose-4-Epimerase (38, 40, 41, 42, 43) from E. Colt B...

Figure 14. Common features of the TDPG-oxidoreductase, UDP-galactose-4-epimerase, and UDP-glucuronic acid carboxylase...

The UDP-galactose is converted back to UDP-glucose by UDP-galactose 4-epimerase. Thus, overall, UDP-glucose is not consumed in the reaction pathway. 

Galactose is isomerized to glucose by UDP-galactose-4-epimerase in what may be the rate-limiting step in galactose metabolism. The reaction, which is freely... 

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