The formation of citric and α-ketoglutaric acids in the mammalian body

Abstract

FROM experiments reported in a previous paper [Krebs & Johnson, 1937] we concluded that carbohydrate is oxidized in animal tissues through the following series of reactions: Oxaloacetic acid + carbohydrate derivative / \ (pyruvic acid?) l-Malic acid Citric acid t Fumaric acid a-Ketoglutaric acid Succinic acid Greville [1936] and Weil-Malherbe [1937] have recently suggested that succinic dehydrogenase may be protected from malonate in the structurally intact tissue. Our experiments show, however, an inhibition of succinic dehydrogenase in the intact body.Maleic acid causes an increased citric acid excretion in Orten & Smith's and our experiments (Table II). It is probable that maleic acid, too, is an enzyme poison, but we cannot exclude the possibility that it acts as a precursor like fumaric acid. Thunberg [1920] and Laki [1935] reported that maleic acid is metabolized in animal tissues. SUMMARY 1. Citric and a-ketoglutaric acids appear in the urine of rabbits and rats after injection of succinic, fumaric, 1(-)-malic or oxaloacetic acids. This is considered to be evidence in support of the "citric acid cycle".

Response of Citric Acid Levels to Oral Administration of Glucose. Ii. Abnormalities Observed in the Diabetic and Convulsive State 1

“…Addition of malonic acid to tissue in vitro will cause a rise in citric acid (14,15). Injection of malonic acid into normal dogs causes a rise in citric acid serum levels (10).…”

The Tricarboxylic acid cycle (revision number 24)

“…without disintegrating the tissue (although in some cases permeability barriers may prevent the penetration of the inhibitor to the site of the enzymes). Malonate has been found to inhibit the respiration of all animal tissues, and the expected accumulation of succinate is found even when the inhibitor is injected into the intact organism 9,10 . These observations may be taken as independent proof of the participation of succinic dehydrogenase in the respiration of animal tissues.…”

The importance of animal studies in Exercise Science

“…Current knowledge on energy metabolism is owed to Krebs, who described for the first time in 1937 the citric acid cycle (Krebs Cycle). The cycle emerged from studies carried out in the pectoral muscles of pigeons 10 . This discovery remains a hallmark in metabolic biochemistry, and Krebs was granted a Nobel Prize in Medicine in 1953.…”