The effect of fumarate on the respiration of liver and kidney tissue.

THE interesting theory of Szent-Gy6rgyi and co-workers [Annau et al., 1935] that in respiration the system fumarate-oxaloacetate functions catalytically in transporting activated metabolite hydrogen to the cytochrome (WarburgKeilin) system has received support in the experiments of Stare & Baumann [1936]. Using the manometric method with pigeon breast muscle and heart muscle (swine), the latter investigators observed the following: "1. The oxygen uptake of tissues is increased by very small amounts of fumarate and the increase is much greater than can be accounted for by the oxidation of the fumarate itself. 2. Small amounts of added fumarate are detectable after prolonged contact with respiring tissue. 3. The increased respiration is normal, that is, the respiratory quotient is not materially changed by the addition of small amounts of fumarate. 4. Substances which yield fumarate on contact with tissue-succinate, malate, oxaloacetate-show a similar action to fumarate itself." Recently Szent-Gy6rgyi and co-workers [Annau et at., 1936] have applied quantitative methods for the micro-estimation of oxaloacetic, pyruvic, and malic acids and have given additional evidence in support of their theory. They followed chemically the disappearance of oxaloacetic acid added to muscle and observed a simultaneous increase in malic acid, with only a very small increase in pyruvic acid. They are of the opinion that most of this pyruvic acid comes from the oxidation of a triose or triosephosphate and not from the decarboxylation of the added oxaloacetate. They have also shown chemically that oxaloacetate is formed in muscle tissue from added fumarate. These findings are of fundamental importance since they give chemical indication of the mechanism of the catalytic action of fumarate and related compounds in respiration. The writer had the opportunity of spending some time in Prof. SzentGydrgyi's laboratory and of repeating and confirming the basic chemical estimations recently given. It is the object of this paper to report on manometric and chemical experiments which show the applicability of the fumarateoxaloacetate catalytic theory to the respiration of the liver and kidney tissue of the rabbit. Methods.