Decarboxylation of pyruvic acid

Aerobic living features metabolize sugars and fatty acids to carbon dioxide. Accordingly, there are some kinds of decarboxylation reactions. TPP-mediated decarboxylation of pyruvic acid to acetaldehyde is one of the most important steps of the metabolism of sugar compounds (Fig. 1). When the intermediate reacts with lipoic acid instead of a proton, pyruvic acid is converted to acetylcoenzyme A, which is introduced to TCA cycle (Fig. 2). 

This is the decarboxylation of a (3-keto acid which undergoes smoothly even in the absence of an enzyme. Thus, it can be said that the mother nature utilizes an organic reaction with a low activation energy. The second step of the decarboxylation is the conversion of a-ketoglutaric acid to succinic acid (Fig. 3). This is the same type of reaction as the decarboxylation of pyruvic acid. 

These enzymes catalyse the non-hydrolytic cleavage of bonds in a substrate to remove specific functional groups. Examples include decarboxylases, which remove carboxylic acid groups as carbon dioxide, dehydrases, which remove water, and aldolases. The decarboxylation of pyruvic acid (10.60) to form acetaldehyde (10.61) takes place in the presence of pyruvic decarboxylase (Scheme 10.13), which requires the presence of thiamine pyrophosphate and magnesium ions for activity. 

Similarly, the pyruvate dehydrogenase complex (PDC) can be activated directly by electrogenerated methyl viologen radical cations (MV +) as mediator. Thus, the naturally PDC-catalyzed oxidative decarboxylation of pyruvic acid in the... 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

Scheme 6. Coenzymes Thiamine Pyrophosphate and Its Role in the Decarboxylation of Pyruvic Acid...

Assisted decarboxylation of pyruvic acid by thiamine pyrophosphate (only the thiazole portion of the coenzyme is shown)... 

Vitamin Influences. The involvement of NAD and NADP in many carbohydrate reactions explains the importance of nicotinamide in carbohydrate melaholism. Thiamine, in the form or thiamine pyrophosphate (cocarboxylase), is the cofaclor necessary in the decarboxylation of pyruvic acid, in the iraru-kelolase-calalyzed reactions of the pentose phosphaie cycle, and in the decarboxylation of alpha-keloglutaric acid in the citric acid cycle, among other reactions. Biotin is a hound cofaclor in the fixation of carbon dioxide to form nxalacetic acid from pyruvic acid. Pantothenic acid is a part of the C oA molecule. There are separate alphabetical entries in this volume on the various specific vitamins as well as a review entry on Vitamin. 

Decarboxylation of pyruvic acid and its isomers, including the enol tautomers and enantiomeric lactone structures, has been investigated at the B3LYP/6-311+- -G(3df, 3pd) level.18 It has been found that a keto form with trans CmethyiCketoCacidOhydroxyi and cis CketoCacidOH, and with one methyl hydrogen in a synperiplanar position with respect to the keto oxygen, is the most stable. 

In general, acidic proteinoids are more active than lysine-rich proteinoids for this reaction. Thermal poly(glutamic acid, threonine) and thermal Poly(glutamic acid, leucine) are the most active of these tested 20>. The activity is gradually decreased by progressive acid hydrolysis20. Compared with natural enzymes, the activity of proteinoid is weak. However the decarboxylation of pyruvic acid by proteinoid obeys Michaelis-Menten kinetics as expressed by the Lineweaver-Burk plot201. In this reaction a small amount of acetaldehyde and acetoin are formed in addition to acetic acid and C02 201. 

CO2 i.r. fluorescence used to study energy disposal in 517 the laser-induced decarboxylation of pyruvic acid. 193 and 248 nm excitation shown to produce COj vibration-ally excited in vj, in contrast with observations at 308 and 351 nm... 

In this case, although the hypothetical balanced process yields a net 4 moles of methanol and 2 moles of CO2 per mole of glucose converted, twice the reducing power is needed compared to the ethanol case and cleavage of two additional carbon-carbon bonds is also required. Decarboxylation of pyruvic acid has not been reported to proceed in this manner. These observations, however, do not preclude the possibility of other biochemical pathways and intermediates to fermentation methanol. 

Similarly, the pyruvate (oxidase) dehydrogenase complex (PYOX) can be activated directly by electrogenerated methyl viologen radical cations (MV" ) as mediator. Thus, the naturally PYOX-catalyzed oxidative decarboxylation of pyruvic acid in the presence of coenzyme A (HSCoA) to give acetylcoenzyme A (acetyl-SCoA) (see section on oxidases) can be reversed. In this way, electroenzymatic reductive carboxylation of acetyl-SCoA is made possible (Fig. 15). 

Krampitz and Hardebeck (48) and Hardebeck et al. (19) have found that thermal polyamino acids accelerate the decarboxylation of pyruvic acid. Carbon dioxide (from C-1 of p5n uvate) and acetic acid (from C-2 and C-3 of pyruvate) were the main products. Small amounts of acetaldehyde and acetoin were also detected. The finding of acetic acid as a main product indicates, as the authors pointed out, that an oxidation as well as a decarboxylation must occur. The process is thus somewhat similar to that observed by Fox and Krampitz (46) with... 

Fio. 9. Influence of hydrolysis of proteinoid on activity for decarboxylation of pyruvic acid. One-hundred percent activity is that of intact proteinoid 0% activity is the same as that of amino acid mixture. Taken from Hardebeck et al. (19). 

Reactions taking place in a model solution containing malvidin 3-0-glucoside, (-)-epicatechin and acetaldehyde was explored by HPLC/DAD and HPLC/ESI-MS analysis 29). Acetaldehyde is a product of yeast metabolism but may also result from ethanol oxidation or from decarboxylation of pyruvic acid during fermentation of grapes (43). 

A quantitative study of the photochemical decarboxylation of pyruvic acid (108) has shown that the formation of products, e.g. (109), is more efficient at lower pH. This effect is interpreted... 

The mechanism of decarboxylation of pyruvic acid is shown in Scheme Xll. The first step is formation of the anion, which then adds to C-2 of pymvate, forming a covalent adduct. This compound has been prepared chemically and its... 

Pyruvate decarboxyiase Decarboxylation of pyruvic acid CH3COCOOH CH3CHO + CO2 None... 

Pyruvate oxidase Oxidative decarboxylation of pyruvic acid CH3COCOOH CH3COOH or to CH3COOPO3 + CO2 FAD... 

Pyruvate ferredoxin oxidoreductase Oxidative decarboxylation of pyruvic acid CH3COCOOH + Fe4S4 + CoASH CH3C0SC0A + CO2 Fe4S4 clusters, coenzyme A... 

The mechanism of the photoinduced decarboxylation of pyruvic acid has been reinvestigated and accounted for via electron transfer from an excited to a ground state molecule. Quantum yields of triplet production at 295 K in deoxygenated benzene, acetonitrile, and water are 0.65, 0.88, and 0.22, respectively. ... 

The enzymic decarboxylation of pyruvic acid, assisted by thiamin pyrophosphate (TPP) or vitamin Bl, produces ethanal, which is reduced... 

Cobalt is well known for its ability to break an oxidatively destructive chain reaction catalysed by another metal (cf. Baur and Preis, 1936). This suggested to the Dutch workers that the iron and copper complexes of oxine, pyrithione, and dimethyldithiocarbamic acid were oxidatively destroying thioctic acid (dihydrolipoic acid) (2.28) which is the essential coenzyme for the oxidative decarboxylation of pyruvic acid. This was confirmed when they found pyruvic acid accumulating in the medium (Sijpesteijn and Janssen, 1959 also personal communications from these authors). The receptor in all three examples is the small molecule (2.28) although, at the time, it caused surprise to find one of such low molecular weight. 

The accumulation of pyruvic acid in treated Aspergillus points to the molecular site of action of DMDC, oxine, and pyrithione, namely catalysis of the oxidative destruction of dihydrolipoic acid [thioctic acid 2.28) (Sijpesteijn and Janssen, 1959). This is the essential coenzyme for oxidative decarboxylation of pyruvic acid by dihydrolipoylacetyltransferase, a component of the multienzyme complex known as pyruvate dehydrogenase. 

Goenzyme of the yeast enzyme, carboxylase. Cryst. from EtOH containing HQ. M.p. 240° Catalyses the decarboxylation of pyruvic acid, fauber, J. Am. Chem. Soc., 1938, 60, 730. Tauber, Weiljard, J. Am. Chem. Soc., 1938, 60, 2263. 

The decarboxylation of pyruvic acid is an example of a more general type of biochemical reaction the decarboxylation of a-keto acids. The reaction is complex and occurs in several consecutive steps. The intermediates have been identified, but little is known of the enzymes involved. The reaction starts with the complexion of pyruvic acid with one molecule of enzyme-bound thiamine pyrophosphate. This is followed by decarboxylation of pyruvic acid and the formation of an intermediate, 2-acetylthiamine pyrophosphate, in which the aldehyde carbon of the acetyl is bound to the carbon 2 of the thiozole ring of the thiamine pyrophosphate. In the second step, the aldehyde is oxidized, the disulfide bond of enzyme-bound lipoic acid is reduced, and the free enzyme-bound thiamine pyrophosphate is restored. The tWrd step of the reaction involves the transacylation from reduced lipoic acid to CoA. Finally, lipoic acid is reoxidized by the catalytic activity of an NAD-dependent flavoprotein, lipoic dehydrogenase (see Fig. 1-14). 

Mizuhara [65] developed a more adequate model by demonstrating that thiamine catalyzes the decarboxylation of pyruvic acid in basic aqueous solution (pH 8.8). Acetoin is the final product of the reaction. Breslow [66] later showed that the hydrogen in position 2 of the thiazole ring of the coenzyme is exchanged with deuterium when deuterium oxide (D2O) is added to the incubation system. Thus, carbon 2 of the thiamine appears to react in this chemical process. The hydrogen in position 2 is acidic and is thus readily ionized to an anion in basic media (see Fig. 4-7). On the basis of these findings, researchers have proposed the following sequence of reactions to explain the catalytic action of carboxylase. The carbon 2 of the thiazo-... 

Many of these deficiency conditions in animals can be explained in terms of the role of TPP in the oxidative decarboxylation of pyruvic acid. On a thiamin-deficient diet animals accumulate pyruvic acid and its reduction product lactic acid in their tissues, which leads to muscular weakness. Nerve cells are particularly dependent on the utilisation of carbohydrate and for this reason a deficiency of the vitamin has a particularly serious effect on nervous tissue. Since acetyl coenzyme A is an important metabolite in the synthesis of fatty acids (see p. 220), lipogenesis is reduced. The pentose phosphate pathway is also impaired by a deficiency of thiamin but there is little effect on the activity of the citric acid cycle. 

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