Oxaloacetic acid

Oxidation. Succinic acid reacts with hydrogen peroxide, giving different products that depend on the experimental conditions peroxysuccinic acid [2279-96-1] (CH2COOOH)2, oxosuccinic acid [328-42-7] (oxaloacetic acid) malonic acid [141-82-2] or a mixture of acetaldehyde, malonic acid, and make acid [6915-15-7]. Succinic anhydride in dimethylformamide (DMF) with H2O2 gives monoperoxysuccinic acid [3504-13-0], HOOCCH2CH2COOOH, mp 107°C (70). 

Potassium permanganate oxidizes succinic acid to a mixture of malic and tartaric acid [133-37-9]. 3-Hydroxypropionic acid [503-66-2] is obtained with sodium perchlorate. Cerium(IV) sulfate in sulfuric acid medium oxidizes succinic acid to oxaloacetic acid (71). 

Fig. 2. Kiebs (citiic acid) cycle. Coenzyme A is lepiesented CoA—SH. The cycle begins with the combination of acetyl coenzyme A and oxaloacetic acid to...

Oxoglutaric acid (2-oxopentane-l,5-dioic, a-ketoglutaric acid) [328-50-7] M 146.1, m 114 , 115-117 , (pK ,( see oxaloacetic acid above). Crystd repeatedly from Me2CO/ benzene, EtOAc or ethyl propionate. 

Oxaloacetic acid, an important intermediate in food metabolism, has the formula C4H4O5 and contains three C=0 bonds and two O-H bonds. Propose two possible structures. 

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

This cycle is a series of reactions starting from the reaction of oxaloacetic acid with acetylcoenzyme A and finally regenerates oxaloacetic acid again, forming two moles of carbon dioxide during one cycle. The first step of the decarboxylation is conjugated with the oxidation of isocitric acid (Fig. 3). 

Thalji NK, Crowe WE, Waldrop GL (2009) Kinetic mechanism and structural requirements of the amine-catalyzed decarboxylation of oxaloacetic acid. J Org Chem 74(1) 144—152... 

It was observed that glutamate and aspartate are diverted predominantly to the synthesis of cell substance rather than to the formation of oxalate. It is not inconsistent to see oc-ketoglutarate being formed from glutamate, while no oxaloacetic acid can be detected in the medium containing aspartate, as the oxaloacetic acid is known to be extremely unstable (2), (62), (Hi). The relatively low yields of oxalic acid, derived... 

The formation of oxaloacetic acid by dehydrogenation implies that this acid may be dissimilated by two mechanisms. It is known (62), (114) that oxaloacetic acid is subject to decarboxylation under acid conditions, and that higher pH is favorable to its stability. Thus, alkaline media enable the add to remain unchanged long enough to be split, yielding acetate and oxalate, while acidic media cause decarboxylation. 

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 ... 

Oxalic Acid Oxaloacetic Acid Pyruvic Acid... 

These considerations allow for a cyclic mechanism to occur in the formation of oxalic acid, where oxaloacetic acid yields either oxalate and acetate, which may be reoxidized, or pyruvate, which will then in turn yield acetate. This is illustrated in the following phase sequence of oxalate formation by these organisms ... 

Biotin s biochemical role is becoming clearer. As mentioned, biotin has been implicatfd in C02-fixation. Good examples for this reaction in animals are (a) the combination of pyruvic acid and C02 to form oxaloacetic acid, or aspartic acid (B26, H19) to replace biotin, and (b) the growth stimulation of certain bacteria in the presence of biotin, and bicarbonate (LI). 

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... 

By the beginning of October that year results from Johnson s experiments allowed Krebs to report at a Biochemical Society meeting in Cambridge If pyruvic acid is added to tissues under anaerobic conditions, together with malic acid or oxaloacetic acid, very considerable quantities of citric acid are formed. ... 

Besides Szent-Gyorgi and Krebs, other groups were attacking the problem of carbohydrate oxidation. Weil-Malherbe suggested It is probable that the further oxidation of succinic acids passes through the stages of fumaric, malic, and oxaloacetic acid pyruvic acid is formed by the decarboxylation of the latter and the oxidative cycle starts again. K.A.C. Elliott, from the Cancer Research Laboratories at the University of Pennsylvania, also proposed a cycle via some 6C acid. 

In June, 1937 Krebs sent a letter to Nature entitled The Role of Citric Acid in Intermediate Metabolism of Animal Tissues. It stated Triose reacts with oxaloacetic acid to form citric acid and in the further course of the cycle oxaloacetic acid is regenerated. The net effect of the cycle is the complete oxidation of triose. Because he had received a surplus of letters, the editor wrote to Krebs that he would be unable to publish the communication for 7 to 8 weeks. The paper with some modifications and additions was therefore submitted to, and accepted by, Enzymologia. 

O Ketoacidosis is a dangerous condition that is characterized by the acidification of the blood and an acetone odour on the breath. The condition occurs when levels of oxaloacetic acid for the citric acid cycle are low. This leads to a buildup of acetyl CoA molecules, which the liver metabolizes to produce acidic ketone bodies. Since carbohydrates are the main source of oxaloacetic acid in the body, high-protein, low-carbohydrate diets have been linked to ketoacidosis. 

Pyruvate carboxylase (also called PC) is an enzyme that converts pyruvate to oxaloacetate (shown as oxaloacetic acid in the citric acid cycle diagram). Pyruvate carboxylase deficiency is a genetic disorder that is characterized by insufficient quantities of pyruvate carboxylate in the body. How do you think this disorder affects the citric acid cycle Use print and electronic resources to research pyruvate carboxylase deficiency. Find out what its symptoms are, and how it affects the body at the molecular level. Also find out what percent of the population is affected, and how the deficiency can be relieved. Present your findings as an informative pamphlet. If possible, conduct an e-mail interview with an expert on the disorder. 

A similar aldol reaction is encountered in the Krebs cycle in the reaction of acetyl-CoA and oxaloacetic acid (see Section 15.3). This yields citric acid, and is catalysed by the enzyme citrate synthase. This intermediate provides the alternative terminology for the Krebs cycle, namely the citric acid cycle. The aldol reaction is easily rationalized, with acetyl-CoA providing an enolate anion nucleophile that adds to the carbonyl of oxaloacetic acid. We shall see later that esters and thioesters can also be converted into enolate anions (see Section 10.7). 

One interesting feature here is that both acetyl-CoA and oxaloacetic acid have the potential to form enolate anions, and that oxaloacetic acid is actually more acidic than acetyl-CoA, in that there are two carbonyl groups flanking the methylene. That citrate synthase achieves the aldol reaction as shown reflects that the enzyme active site must have a basic residue appropriately positioned to abstract a proton from acetyl-CoA rather than oxaloacetic acid, thus allowing acetyl-CoA to act as the nucleophile. 

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). 

Biotin (5) is the coenzyme of the carboxylases. Like pyridoxal phosphate, it has an amide-type bond via the carboxyl group with a lysine residue of the carboxylase. This bond is catalyzed by a specific enzyme. Using ATP, biotin reacts with hydrogen carbonate (HCOa ) to form N-carboxybiotin. From this activated form, carbon dioxide (CO2) is then transferred to other molecules, into which a carboxyl group is introduced in this way. Examples of biotindependent reactions of this type include the formation of oxaloacetic acid from pyruvate (see p. 154) and the synthesis of malonyl-CoA from acetyl-CoA (see p. 162). 

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