Phosphohistidine

Abstract

The discovery of protein-bound phosphohistidine and its mode of formation from both Pj and ATP in intact mitochondria and in soluble enzyme preparations from mitochondria gives convincing evidence that the phosphorylated imidazole group of a bound histidine is an intermediate in oxidative phosphorylation. The suggestion is warranted on the basis of these findings together with other data that all phosphorylation of oxidative phosphorylation occurs in a mechanistically similar process in which electron transport is coupled to formation of an activated imidazole structure, possibly an acyl imidazole. The activated imidazole structure is cleaved by Pi to form bound phosphohistidine, which can react with ADP to give ATP and bound histidine, in readily reversible reactions. The activated imidazole structure is also considered to serve as a common reactant in various energy-linked reductions in a new means of energy transfer in cells. Many properties of oxidative phosphorylation and its inhibition correlate well with the suggestions made, except that the magnitude of phosphorus-oxygen ratios may need further consideration (37).