Metabolism of ketonic acids in animal tissues

Abstract

IN this paper experiments are described which show that ketonic acids can react in animal tissues according to the general scheme R. CO.COOH + R'. CO. COOH + H20-R. COOH + C02 + R'. CH(OH). COOH ...... (1) oa-ketonic a-ketonic carboxylic a-hydroxy-acid acid I acid II acid or R. CO. COOH + R'. CO. CH2. COOH + H20-R. COOH + CO2 + R'. CH(OH) .C0. COOH ....(2). ae-ketonic fl-ketonic acid carboxylic ,-hydroxy-acid acid acid Examples are given in which oc-ketonic acid I as well as a-ketonic acid II in (1) are represented by pyruvic acid. In other cases the oc-ketonic acid in (2) is pyruvic acid or a-ketoglutaric acid and the ,B-ketonic acid in (2) acetoacetic or oxaloacetic acid. The reactions 1 and 2 elucidate a mechanism by which ac-ketonic acids are broken down in the animal body. Although it has long been known, from the work of Embden, that oc-ketonic acids undergo oxidation to the fatty acids which are shorter by one carbon atom, the question of the mechanism of this oxidation remained open. According to (1) and (2) the oxidation of a-ketonic acids is not brought about by molecular oxygen, but by a dismutation, that is to say by an intermolecular oxido-reduction. The oxidizing agent for the ketonic acid is a second molecule of ketonic acid which is reduced to the corresponding hydroxy-acid. The reactions (1) and (2) appear to play a role in the course of the normal oxidative breakdown of carbohydrates, of fats and of the carbon skeleton of amino-acids. This will be discussed in full in subsequent papers. I. GENERAL EXPERIMENTAL METHODS 1. Determination of cx-ketonic acids (a) Carboxylase method. Pyruvic acid was usually determined by the carboxylase method [Warburg et al. 1930; Westerkamp, 1933]. Freshly pressed top yeast obtained from a local brewery was spread over filter-paper and dried at room temperature with the aid of a fan. The dried yeast, treated according to the directions of Westerkamp, yielded a powerful carboxylase. The addition of 1/5 vol. of 90 % glycerol stabilized the enzyme for about one week at 0°[see von Schoenebeck, 1935]. It is essential that the yeast used should be fresh and quickly dried [Wiilfert, 1936]. (b) Ceric sulphate method. An alternative method applicable to other oc-ketonic acids is based on the reaction R. CO. COOH + 2Ce +H20-R. COOH + CO2 + 2Ce" + 2R

The formation of glucose from acetoacetic acid in rat kidney

“…Formation of reducing Annau [1935] for liver, muscle and kidney; Weil-substance (cal. as glucose) Malherbe [1936] for brain; Krebs & Johnson [1937] It is confirmed that no acetol is formed from acetoacetic acid, whereas the reducing substance formed from dihydroxybutyric acid is largely acetol, only a minute fraction being glucose.…”

Respiratory metabolism of illuminated leaves depends on CO 2 and O 2 conditions

“…The inhibition of the PDH-mediated decarboxylation was relatively constant under the CO 2 and O 2 conditions investigated. In contrast, TCA-mediated decarboxylations were much more sensitive to low CO 2 Table 1). This finding indicated that [ 13 C]Glc could be oxidized in the light by glycolysis and that PDH and TCA activities were both at the origin of the respired 13 CO 2 from […”

“…isotope ͉ photosynthesis ͉ regulation ͉ respiration ͉ photorespiration I t has been 70 years since Krebs and Johnson (1,2) proposed the mechanism by which pyruvic acid is oxidized to CO 2 , which is now called the ''Krebs cycle'' or tricarboxylic acid (TCA) cycle. Whereas the basics of the metabolic reactions involved in leaf respiration are known, intense efforts are still currently devoted to elucidating the regulation of the TCA cycle (and, more generally, of day respiration) in illuminated leaves (for a recent review, see ref.…”

Studies on the Metabolism of the Filarial Worm, Litomosoides Carinii

“…CO-COOH + H,O --* CI-Iv CHOH. COOH + CHv COOH + CO2 This dismutation of pyruvate to lactate, acetate, and CO2 has also been demonstrated to occur in brain (28) and in certain bacteria (29,30).…”