Oxalosuccinate

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

Step 3 of Figure 29.12 Oxidation and Decarboxylation (2K,3S)-lsocitrate, a secondary alcohol, is oxidized by NAD+ in step 3 to give the ketone oxalosuccinate, which loses C02 to givea-ketoglutarate. Catalyzed by isocitrate dehydrogenase, the decarboxylation is a typical reaction of a /3-keto acid, just like that in the acetoacetic ester synthesis (Section 22.7). The enzyme requires a divalent cation as cofactor, presumably to polarize the ketone carbonyl group. 

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 ... 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

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). 

In isocitrate, there is a CHOH group that is available for oxidation via the coenzyme NAD+ and the enzyme isocitrate dehydrogenase. NADH will then be reoxidized via oxidative phosphorylation, and lead to ATP synthesis. The oxidation product from isocitrate is oxalosuccinate, a -ketoacid that easily... 

I. 1.1.42], also known as oxalosuccinate decarboxylase, catalyzes the reaction of isocitrate with NADP+ to produce a-ketoglutarate, carbon dioxide, and NADPH. The enzyme is reported to be able to decarboxylate added oxalosuccinate. 

Manganese is an essential element for plants and animals. Its shortage in soil can cause chlorosis or lack of chlorophyll in plants—manifested by the appearance of yellow or grey streaks on the leaves or mottling. It activates certain plant enzymes, such as oxalosuccinic decacarboxylase in the oxidation of carbohydrates. Manganese deficiency can cause deformity of bones in animals. 

The first oxidative conversion of the TCA cycle is catalyzed by isocitrate dehydrogenase. This conversion takes place in two steps oxidation of the secondary alcohol to a ketone (oxalosuccinate), followed by a j8 decarboxylation to produce a-ketoglutarate (fig. 13.9). 

NAD+ is the electron acceptor for the oxidative step, and Mg2+ or Mn2+ is required for the decarboxylation. The oxalosuccinate that is presumably an intermediate does not dissociate from the enzyme. 

The oxidative decarboxylation of isocitrate to a-kctoglutaratc, catalyzed by mitochondrial isocitrate dehydrogenase. The intermediate, oxalosuccinate, is not released from the enzyme. B represents a catalytic side chain from the enzyme. 

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

The intermediate in this reaction, oxalosuccinate, does not dissociate from the enzyme and is not usually classed as a discrete intermediate of the citric acid cycle. 

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