Alloxan action on glucose metabolism in cultured fibroblasts. II. Effects on pentose-monophosphate shunt and tricarboxylic acid pathways.

The site of action of alloxan on glucose metabolism has been investigated using cultured human fibroblasts. Analysis of cell extracts after cell monolayers were exposed to D-[U-14C]glucose indicated that the initial stimulation of glucose incorporation by alloxan was observed primarily in the nucleotide fraction (ribose) with inhibition of lactate production. The subsequent inhibition of glucose incorporation was observed in the nucleotide fraction. Assay of 14CO2 production indicated that alloxan enhanced 14CO2 formation from D-[U-14C]glucose for approximately 10 min, followed by inhibition. To probe the site of alloxan action, rates of 14CO2 formation from 1- and 6-position labeled [14C]glucose, and [U-14C]pyruvate were compared. The initial stimulation was observed mainly in D-[1-14C]glucose oxidation, whereas inhibition was measurable with the 6-position tracer and [14C]pyruvate. The results suggest that alloxan initially stimulates the pentose-monophosphate shunt and then subsequently inhibits both the pentose-monophosphate shunt and tricarboxylic acid pathways.