Oxaloacetic acid, decarboxylation

Also, Flesch and Holbach (15) showed that malic enzyme activity was inhibited by parachloromercuribenzoate, but oxaloacetic acid decarboxylation was not. 

In Leuconostoc oenos ML 34, we have shown oxaloacetic acid decarboxylation manometrically (6, 7, 8). We were also able to demonstate fluorometrically the enzymatic production of reduced NAD with malic acid as a substrate, but, of course, were unable to do so with oxaloacetic acid since no NADH could be formed from this substrate. It is likely that this oxaloacetic acid decarboxylation activity, as in Lactobacillus plantarum, is distinct from the activity causing the malic-lactic transition. It is also possible that oxaloacetic acid decarboxylation is caused by a malic enzyme. However, there is no verified NAD dependent malic oxidoreductase (decarboxylating) enzyme which does so (12). For example, Macrae (31) isolated a malic enzyme from cauliflower bud mitochondria which showed no activity with oxaloacetic acid. Similarly, Saz (32) isolated a malic enzyme from Ascaris lumbricoides which is also inactive toward oxaloacetic acid. True, the Enzyme Commission (12) lists an enzyme described as L-malate NAD oxidoreductase (decarboxylating) (E.C. 1.1.1.38) which is said to be capable of decarboxylating oxaloacetic acid, but its description dates back to the studies of Ochoa and his group, and we now feel this listing may be improper. 

Osmium, quinuclidinetetraoxime-stereochemistry, 44 Osmium, tetrachloronitrido-tetraphenylarsenate stereochemistry, 44 Osmium, tris( 1,10-phenanthroline) -structure, 64 Osmium(II) complexes polymerization electrochemistry, 488 Osmium(III) complexes magnetic behavior, 273 Osmium(lV) complexes magnetic behavior, 272 Osmium(V) complexes magnetic behavior, 272 Osmium(VI) complexes magnetic behavior, 272 Oxaloacetic acid decarboxylation metal complexes, 427 Oxamidoxime in gravimetry, 533 Oxidation-reduction potentials non-aqueous solvents, 27 Oxidation state nomenclature, 120 Oxidative addition reactions, 282 Oxidative dehydrogenation coordinated imines, 455 Oximes... 

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... 

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. 

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. 

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). 

The most important apphcation of this metal is as control rod material for shielding in nuclear power reactors. Its thermal neutron absorption cross section is 46,000 bams. Other uses are in thermoelectric generating devices, as a thermoionic emitter, in yttrium-iron garnets in microwave filters to detect low intensity signals, as an activator in many phosphors, for deoxidation of molten titanium, and as a catalyst. Catalytic apphcations include decarboxylation of oxaloacetic acid conversion of ortho- to para-hydrogen and polymerization of ethylene. 

A model system and mechanism (12) had also been developed for the metal-ion promoted enzymic decarboxylations of dibasic ketoacids, such as oxaloacetic acid (Steinberger and Westheimer, 1949,1951). 

Although metal ions do not catalyze the decarboxylation of monocarboxylic acids in solution, a variety of metal ions catalyze the decarboxylation of oxaloacetic acid anion, leading to the formation of pyruvic acid (27). The metal ions involved were cupric, zinc, magnesium, aluminum, ferric, ferrous, manganous, and cadmium, approximately 10-2 to 10-3 M (27). Of these, the aluminum, ferric, ferrous, and cupric ions were the most efficient sodium, potassium, and silver ions were inactive. This process involves the decarboxylation of a / -keto acid, which undergoes a relatively facile uncatalyzed decarboxylation. However, not every decarboxylation of a / -keto acid is catalyzed by metal ions—only those... 

To elucidate the difference between the enzymatic and nonenzymatic participation of metal ions, it is clearly desirable to be able to compare the effect of a large number of metal ions upon the same reaction both in the presence and absence of the enzyme. For such a study to be feasible it is necessary to work with a metal-activated enzymatic reaction, which will also take place when the metal, but not the enzyme, is omitted. Such a reaction is the decarboxylation of oxaloacetic acid. The mechanism of metal catalysis of this reaction is similar to that assumed for carboxypeptidase, and can be represented as follows (44). 

The studies on the methylation of dihydroxybenzaldehyde and the earlier studies on the decarboxylation of oxaloacetic acid illustrate a hypothesis about metal-catalyzed enzymes that is not proved but has been substantiated in a number of instances in which it has been tried. The hypothesis is that, if a metal constitutes the active site of an enzyme, it should be possible to carry out the reaction with metal ions alone in the absence of the enzyme. The rates of non-enzymatic reactions may be much lower, and the metal ions may be more active metal ions than those that activate the enzyme, for the reasons already discussed. This hypothesis is the basis for much of the work on metal catalytic reactions that are models for enzyme systems. 

Oxaloacetic acid [328-42-7] M 132.1, m 160°(decarboxylates). Crystd from boiling ethyl acetate, or from hot acetone by addition of hot benzene. 

NADH as an end product. This implicates oxidized malic acid, either pyruvic or oxaloacetic acid, as another end product. By adding commercial preparations of L-lactic dehydrogenase or malic dehydrogenase to the reaction mixture, Morenzoni (90) concluded that the end product was pyruvic acid. Attempts were then made to show whether two enzymes—malate carboxy lyase and the classic malic enzyme, malate oxidoreductase (decarboxylating), were involved or if the two activities were on the same enzyme. The preponderance of evidence indicated that only one enzyme is involved. This evidence came from temperature inactivation studies, heavy-metal inhibition studies, and ratio measurements of the two activities of partially purified preparations of Schiitz and Radlers malo-lactic enzyme (76, 90). This is not the first case of a single enzyme having two different activities (91). 

When considering the mechanism of the malo-lactic fermentation, the possibility that malic acid may be converted first to oxaloacetic acid (by malic dehydrogenase) must be recognized. This acid could then be decarboxylated to pyruvic acid, and subsequent reaction would yield lactic acid. However, if this were the case, there then should be no situation where malic acid would be decarboxylated faster than oxaloacetic acid. This, however, was shown to occur at pH 6 (14). Similarly, Flesch and Holbach (15) report that malic dehydrogenase has an optimal pH of 10, but that the malo-lactic reaction proceeds at pH 5.6. Therefore, it would not seem likely that the cell would degrade malic acid by this mechanism hence, the oxaloacetic acid intermediate would not be available to the organism. 

It was reported (14) that the adaptive enzyme from Lactobacillus plantarum could decarboxylate oxaloacetic acid as well as malic acid. However, in the same organism, Nathan (30) carried this work further and showed that the oxaloacetate decarboxylase activity is not related at all to the malic acid-lactic acid transformation activity. She based this conclusion on the ability of malic and oxaloacetic acids to induce oxaloacetate decarboxylase activity as well as malic enzyme activity. In her words,... 

Decarboxylation of p-oxoacids. Beta-oxoacids such as oxaloacetic acid and acetoacetic acid are unstable, their decarboxylation being catalyzed by amines, metal ions, and other substances. Catalysis by amines depends upon Schiff base formation,232 while metal ions form chelates in which the metal assists in electron withdrawal to form an enolate anion.233 235... 

Catalytic decarboxylation processes occur in aliphatic keto acids in which the keto group is in an a-position to one carboxyl group and in a P-relationship to another. Thus, the normal decarboxylation of a p-keto acid is facilitated by metal coordination to the a-keto acid moiety. The most-studied example is oxaloacetic acid and it has been shown that its decarboxylation is catalyzed by many metals following the general order Ca2+ < Mn2+ < Co2+ < Zn2+ < Ni2+ < Cu2+ < Fe3+ < Al3"1".66 67 The overall rate constants can be correlated with the stability constants of 1 1 complexes of oxalic acid rather than oxaloacetic acid, as the uncoordinated carboxylate anion is essential for the decarboxylation. The generally accepted mechanism is shown in Scheme 15. Catalysis can be increased by the introduction of x-bonding ligands, which not only increase the... 

Some 25 papers have been published on various aspects of the metal ion-promoted decarboxylation of oxaloacetic acid and its derivatives338-340 and this system can be used to illustrate many features of these reactions. The /3-oxo acids decarboxylate spontaneously in aqueous solution... 

For the decarboxylation of oxaloacetic acid the reactions shown in Scheme 26 can be considered. Early measurements of rate constants (k) and formation constants (XMA) are summarized in Table 24. The copper complex CuA decarboxylates some 9.4 x 102 times faster than the dianion A2-. 

The simplest member of the series of aliphatic a-keto acids is pyruvic acid. It is conveniently prepared by the distillation of tartaric acid with a dehydrating agent such as postassium hydrogen sulphate (Expt 5.173). The reaction probably involves dehydration to the tautomeric oxaloacetic acid (13) intermediate, which then decarboxylates by virtue of its constitution as a / -keto acid. 

Several approaches have been developed for the synthesis of 3-deoxy-D-mararao-oct-2-ulosonic acid (Kdo, 123) the most common one involves the coupling of oxaloacetic acid with D-arabinose followed by decarboxylation. This aldol reaction takes place under basic conditions, but above pH 11 side reactions occur. The procedure is simple and Kdo is isolated as the crystalline ammonium salt.316... 

Here the situation becomes one stage more complex. The acid can form both the anion and dianion and all three species can decarboxylate, e.g., for 2-oxobutanedioic acid (oxaloacetic acid)... 

Question. The decarboxylation of 2-oxobutanedioic acid, p. 341 (oxaloacetic acid), H2A, at constant pH has three contributing steps ... 

Decarboxylation of /3-ketodicarboxylic acids - approximations to the overall rate expression deduced from the mechanism, 341-342 Decarboxylation of oxaloacetic acid - contributions to the overall rate, 342-343 Glycine ethyl ester, metal ion catalysed hydrolysis, formulation of the rate expression, 344-346... 

Proteinoids catalyze the decarboxylation of oxaloacetic acid to pyruvic acid, lysine-rich proteinoid being the most effective of these tested. Some are about 15 times more active than the equivalent amount of free lysine. Acidic proteinoids exhibit very little activity18). 

Proteinoids were tested after being stored in the dry state for 5 to 10 years. Acidic proteinoids effective in catalyzing the hydrolysis of p-nitrophenyl acetate showed the same levels of activity as observed 10 years earlier19>. Lysine-rich proteinoids which catalyzed the decarboxylation of oxaloacetic acid were found to be insoluble in assay medium after 5 years of storage in the dry state. Their activity, however, had increased by 32 to 145%, and the activity of the lysine-rich proteinoids was largely associated with the insoluble portion 19). 

It is clear that biological systems can manage the chemical reactivity of unstable species. For example, oxalo-acetate—a metabolic intermediate in terran metabolism that is a precursor of citric acid, malic acid, and the amino acid aspartic acid—decarboxylates readily, with a half-life measured in minutes at room temperature at neutral pH. The half-life for the decarboxylation of oxaloacetate drops to seconds at high temperatures in pure water. It is not clear how microorganisms that live at high temperatures manage the instability of oxaloacetate, which is a key intermediate in standard biochemistry for the formation of amino acids, such as aspartate, and asparagine. 

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