Oxalosuccinic acid

Another observation on oxalate formation is that other a-keto acids, such as oxalosuccinic acid (74) and a-ketoglutaric acid (106) do not seem to yield oxalate directly but indirectly (123). This appears to be due to the fact that only oxaloacetic acid can function as an acetate donor. In this connection the intervention of Coenzyme A may be considered, since it is reported to function in the acetylation of sulfanilamide and choline (73) and recently was shown to take part in the enzymatic synthesis of citric acid. This concept may be illustrated as follows ... 

L-ascorbic acid and, 25 751 as chelating agent, 5 731 in cocoa shell from roasted beans, 6 357t Oxalic-acid-catalyzed novolacs, in molding compounds, 75 786 Oxalic acid esterification, 72 652 Oxaloacetic acid, in citric acid cycle, 6 633 Oxalosuccinic acid, in citric acid cycle, 6 633... 

The enzyme isocitrate dehydrogenase is one of the enzymes of the Krebs or citric acid cycle, a major feature in carbohydrate metabolism (see Section 15.3). This enzyme has two functions, the major one being the dehydrogenation (oxidation) of the secondary alcohol group in isocitric acid to a ketone, forming oxalosuccinic acid. This requires the cofactor NAD+ (see Section 11.2). For convenience, we are showing non-ionized acids here, e.g. isocitric acid, rather than anions, e.g. isocitrate. 

The second function, and the one pertinent to this section, is the decarboxylation of oxalosuccinic acid to 2-oxoglutaric acid. This is simply a biochemical example of the ready decarboxylation of a P-ketoacid, involving an intramolecular hydrogen-bonded system. This reaction could occur chemically without an enzyme, but it is known that isocitric acid, the product of the dehydrogenation, is still bound to the enzyme isocitrate dehydrogenase when decarboxylation occurs. 

It is appropriate here to look at the structure of oxaloacetic acid, a critical intermediate in the Krebs cycle, and to discover that it too is a P-ketoacid. In contrast to oxalosuccinic acid, it does not suffer decarboxylation in this enzyme-mediated cycle, but is used as the electrophile for an aldol reaction with acetyl-CoA (see Box 10.4). 

Rat urine Myocardial infarction 25 LC-QTOF-MS Creatine Uridine Glutamate Pantothenic acid Oxalosuccinic acid Nicotinamide mononucleotide Phenylacetylglycine Xanthosine Shexiang Baoxin Pill (14)... 

Ochoa has recently reported a new assimilation reaction involving a-ketoglutarate and CO2 to form oxalosuccinic acid. This provides another pathway by which CO2 may be utilized. The mechanisms involved in this new assimilation reaction are thoroughly discussed by Ochoa. 

Some of the earliest kinetic studies on metal ion-promoted reactions were carried out on metal ion-promoted decarboxylations of j8-oxo acids. The literature on this topic up to about 1974 has been reviewed. Much of the work has centred on oxaloacetic acid (HO2CCOCH2CO2H = H20xac) and its derivatives, a,a-dimethyl oxaloacetic acid and fluorooxaloacetic acid. Studies have also been made with acetonedicarboxylic acid (3-oxoglutaric acid), " dihydroxyfumaric acid, dihydroxytartaric acid, acetosuccinic acid, oxalosuccinic acid and 2-oxalopropionic acid (Figure 6). The decarboxylation of )3-oxo acids is of considerable biological importance, and in a number of cases metalloenzymes are involved. Similarities in the enzymatic and chemical processes stimulated early interest in these reactions as models for the enzymatic systems. 

A variety of metal ions have been found to increase markedly the rate of decarboxylation of several jS-keto acids, but to have no effect on the decarboxylation of ketomonocarboxylic acids such as acetoacetic acid. Moreover, only those fl-keto acids having a second carboxylic acid group adjacent to the /3-keto group are affected by the presence of metal ions, e.g., oxaloacetic or oxalosuccinic acids (90, 116, 166, 170, 190, 191, 208). 

Citric acid is isomerized by aconitase to yield isocitric acid (cw-aconitic acid is an intermediate). The oxidation of isocitrate by isocitrate dehydrogenase to a-oxoglutarate involves the formation of NADH (an NADP linked enzyme is also found) and the oxalosuccinic acid produced is de-carboxylated to yield a-oxoglutarate. 

The oxidation of a jS-hydroxyacid with decarboxylation of the j8-ketonic acid formed has already been described above in the case of the passage of isocitric acid into oxalosuccinic acid and then to a-ketoglutaric acid during the tricarboxylic acid cycle. 

In 1948 Ochoa demonstrated the existence of an enzyme, isocitric dehydrogenase, which catalyzed the oxidation of isocitric acid and required NADP. He was, however, unable to demonstrate the formation of the expected product oxalosuccinic acid (Fig. 1). The existence of this acid as an intermediate in the Krebs cycle had been postulated by Carl Martius. Ochoa was able to prepare the compound by chemical synthesis and showed that cell extracts catalyzed the decarboxylation of this very unstable /S-keto acid to a-ketoglutaric acid. Similar results were simultaneously obtained by Lynen in Germany. 

Thus the enzyme had two functions dehydrogenation of isocitric acid, to oxalosuccinic acid, followed by decarboxylation to a-ketoglutaric acid. The second stage of the process could be studied separately because of its dependence on Mn. Ochoa was able to show the reversibility of the process, namely CO2 fixation by a-ketoglutarate and subsequent reduction of the presumed oxalosuccinic acid intermediate. 

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