Metabolism of Inorganic Pyrophosphate. I. Microsomal Inorganic Pyrophosphate Phosphotransferase of Rat Liver.

The formation of large amounts of inorganic pyrophosphate as a by-product of numerous synthetic reactions in nearly all living tissues makes the metabolic reactions of this compound of interest. Rapid hydrolysis to orthophosphate is presumed to be the fate of most inorganic pyrophosphate but the possibility of the conservation and utilization of some of the energy of this compound has been a subject of speculation (1, 2). Whereas a yeast pyrophosphatase has been isolated, crystallized, and extensively studied (3, 4), knowledge of mammalian enzymes acting upon PPi is in a much less satisfactory state. At least four inorganic pyrophosphatases, differing in their pH optima, have been reported to occur in rat liver (5, 6). The properties of a pyrophosphatase occurring in mouse liver particles have been studied (7) and the wide distribution of activity in subcellular fractions of rat liver homogenates has been noted (8). Two distinct pyrophosphatase activities differing in pH optima and Mg+ requirements have been reported to exist in rat liver mitochondria (9). Of particular interest is the finding of Rafter (10) that mouse liver mitochondrial preparations at pH 5.2 are capable of utilizing PPi for the formation of glucose 6-phosphate. Under his optimal conditions the synthetic function represented only a small fraction of the total PPi which was cleaved, but the two activites were parallel. The present paper reports the results of studies of the occurrence, distribution, and some of the properties of the rat inorganic pyrophosphate phosphotransferase enzyme which catalyzes the synthesis of glucose-6-P. The results indicate that the two reactions,