Metabolic inhibition of mammalian uridine diphosphate galactose 4-epimerase in cell cultures and in tumor cells.

The metabolism of galactose compounds, especially that of uridine diphosphate n-galactose, has been studied in intact as well as in broken L cells and HeLa cells. It has been shown that the incorporation of n-galactose l-phosphate into UDP-galactose is rate-limiting in broken cell preparations, whereas the enzymatic 4-epimerization takes place at an appreciable rate. The latter reaction is strongly inhibited by reduced diphosphopyridine nucleotide, especially at a pH close to 7. In intact L cells and HeLa cells, UDP-galactose 4-epimerase is rate-limiting. The intracellular epimerase activity constitutes only about 0.1% of that found under optimal conditions in broken cells. Addition of galactose to these cells brings about a block between the general carbon pool of metabolites and the UDP-hexose pool. This is borne out by the fact that administration to intact L cells or to HeLa cells of W-galactose and 12C-glucose in equimolar amounts brings about incorporation by 14C into UDP-hexose without detectable dilution of nonradioactive glucose. This blockage of the UDP-hexose pool from the general metabolic pool as well as the blockage of UDP-galactose 4-epimerase may have biological implications, some of which are briefly discussed.