ATP-citrate lyase is another enzyme the histidine phosphorylation of which is inhibited by vanadate

We have recently shown that phosphorylation of histidine residue of the alpha-subunit of the succinyl-CoA synthetase is inhibited by both vanadate and vanadyl. To assess the university of this inhibition, we have estimated the effect of vanadate on the phosphorylation of another enzyme ATP-citrate lyase, prepared from rat liver. This enzyme contains histidine as the only amino acid with an acid-labile (P-N) phosphate bond. The 67% inhibition of endogenous phosphorylation by 1 mM vanadate disappeared after cleavage of the acidic P-N bond of histidine with acidic sample solution. The remaining 33 per cent radioactivity was due to labelling of the acid-stable phosphoamino acids (P-serine and P-threonine), the phosphorylation of which was not affected by vanadate. The dose response curve for vanadate inhibition closely resembles that shown previously for inhibition of phosphorylation of histidine in the succinyl-CoA synthetase. The results suggest that the action of vanadate on histidinyl phosphorylation is a more general effect (like its influence on phosphorylation of the protein-bound tyrosine).