The effect of fumarate on respiration
The recent work of Szent-Gyorgyi and his co-workers (Gozsy and Szent-Gyorgyi, 1934; Annau et al .,1935) on the importance of fumarate in cellular respiration assigns a definite and fundamental function to the di-carboxylic four-carbon-atom acids and to the enzymes which activate them. Essentially their view is as follows: the reversible system, fumarate-oxalacetate, functions catalytically in transporting activated hydrogen from the metabolite dehydrogenation systems to the cytochrome (Warburg-Keilin) system through the medium of an intermediary substance. The oxalacetate formed takes up hydrogen, going either to fumarate, or to succinate by “ over-reduction ”. The succinate thus formed is converted to fumarate by means of succinodehydrogenase, and the catalytic cycle is completed. Malonate is known to inhibit succinodehydrogenase (Quastel and Wooldridge, 1928), and malonate also inhibits respiration. SzentGyorgyi et al . explain this inhibition by the fact that the succinate normally formed is prevented by malonate from being oxidized to fumarate, and respiration fails owing to a lack of fumarate. They further attribute the decrease in respiration of muscle tissue in vitro to a loss of fumarate through diffusion. If, however, this loss is compensated for by the addition of fresh fumarate, respiration proceeds normally. The addition of fumarate therefore “ preserves ” the normal respiration of the tissue.