Synthesis of succinate from propionate and bicarbonate by soluble enzymes from liver mitochondria.

Propionic acid has long been known (1, 2) to be a glycogenic substance in animals, but the pathway by which it is converted to intermediates of carbohydrate metabolism has remained obscure. Lorber et al. (3) demonstrated that the ~1and P-carbon atoms of propionate are randomized completely before incorporation into liver glycogen, while those of lactate are not (4). In liver slices, complete randomization of the (Yand p-carbon atoms of propionate occurs during the formation of lactate (5) and acetate (6). Therefore the postulated direct oxidation by animal tissue of propionate, through acrylate and lactate, to pyruvate (7, 8) does not appear to occur to any appreciable extent in the intact animal or in surviving liver. It has been postulated (3, 5, 6) either that propionate is converted to a symmetrical 4-carbon acid by CO2 fixation or that the pyruvate, which might be produced by direct oxidation, is rapidly equilibrated with an unknown symmetrical intermediate. Succinate is decarboxylated to propionate and COO by Propionibacleria and related bacteria (g-11), and the reverse reaction may account for the incorporation of C1402 into succinate by these organisms (12) and for the photosynthetic production of succinate from propionate and CO* by Chlorobium thiosulphutophilum (13). In the present study, which was undertaken to test what at that time was a logical but hypothetical pathway for propionate metabolism (14), the direct conversion of propionate to succinate by COr fixation has been demonstrated with soluble enzymes from mammalian liver. Certain aspects of the work have been reported elsewhere (14-16), while the following paper (17) describes the occurrence of this reaction in intact mitochondria.