Decarboxylation of pyruvate

The TCA Cycle—A Brief Summary The Bridging Step Oxidadve Decarboxylation of Pyruvate Entry into the Cycle The Citrate Syntha.se Reaction The Lsomerizadon of Citrate by Aconita.se... 

Pyruvate produced by glycolysis is a significant source of acetyl-CoA for the TCA cycle. Because, in eukaryotic ceils, glycolysis occurs in the cytoplasm, whereas the TCA cycle reactions and ail subsequent steps of aerobic metabolism take place in the mitochondria, pyruvate must first enter the mitochondria to enter the TCA cycle. The oxidative decarboxylation of pyruvate to acetyl-CoA,... 

The first step of this reaction, decarboxylation of pyruvate and transfer of the acetyl group to lipoic acid, depends on accumulation of negative charge on the carbonyl carbon of pyruvate. This is facilitated by the quaternary nitrogen on the thiazolium group of thiamine pyrophosphate. As shown in (c), this cationic... 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

Figure 17-5. Oxidative decarboxylation of pyruvate by the pyruvate dehydrogenase complex. Lipoic acid is joined by an amide link to a lysine residue of the transacetylase component of the enzyme complex. It forms a long flexible arm, allowing the lipoic acid prosthetic group to rotate sequentially between the active sites of each of the enzymes of the complex. (NAD nicotinamide adenine dinucleotide FAD, flavin adenine dinucleotide TDP, thiamin diphosphate.)...

Ephedrine and pseudoephediine are a vasodilator and decongestant respectively used widely in the treatment of asthma and the symptoms of colds and influenza. These pharmaceuticals were derived originally fi om the plant Ephedra sinica and used in traditional Chinese medicinal preparations. Although some are still produced fi om such sources, the major production is via a fermentation process followed by a chemical catalytic reaction. As shown in Figure 1, the intermediate / -phenylacetylcarbinol (PAC) is produced by decarboxylation of pyruvate followed by ligation to benzaldehyde. 

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. 

Grootveld et al. (1994) employed this technique to investigate radiolytic, damage to biomolecules present in human body fluids. 7-Radiolysis of healthy or rheumatoid human serum (5.00 kGy) in the presence of atmospheric O2 gave rise to reproducible elevations in the concentration of NMR-detectable acetate, which are predominantly ascribable to the prior oxidation of lactate to pyruvate by OH radical followed by oxidative decarboxylation of pyruvate by radiolytically generated H2O2 and/or further OH radicals (Equations 1.7 and 1.8). 

However, at pH values closer to neutrality (i.e. at the mean salivary pH of 5.97), chlorite anion itself can effect the oxidative decarboxylation of pyruvate to acetate and CO2 (Equation 1.12). 

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)... 

The tricarboxylic acid cycle was therefore validated, having been tested not only in pigeon-breast muscle but also with brain, testis, liver, and kidney. The nature of the carbohydrate fragment entering the cycle was still uncertain. The possibility that pyruvate and oxaloacetate condensed to give a 7C derivative which would be decarboxy-lated to citrate, was dismissed partly because the postulated compound was oxidized at a very low rate. Further, work on the oxidation of fatty acids (see Chapter 7) had already established that a 2C fragment like acetate was produced by fatty acid oxidation, en route for carbon dioxide and water. It therefore seemed likely that a similar 2C compound might arise by decarboxylation of pyruvate, and thus condense with oxaloacetate. For some considerable time articles and textbooks referred to this unknown 2C compound as active acetate. ... 

SOME STEPS IN THE TRICARBOXYLIC ACID CYCLE Oxidative Decarboxylation of Pyruvate The Intracellular Function of Vitamin Bj... 

The way in which thiamine participated in the oxidation of pyruvate became clearer when Lohmann and Schuster (1937) showed vitamin Bj to be present intracellularly as thiamine pyrophosphate. In yeast, decarboxylation of pyruvate yielded ethanal which was reduced by alcohol dehydrogenase to give ethanol. A cofactor was needed for this decarboxylation, co-carboxylase. Like the cofactor needed in animal cells for the decarboxylation of pyruvate, cocarboxylase was found to be identical to thiamine pyrophosphate. Vitamin Bj thus became the first vitamin whose intracellular function as a coenzyme had been established in vitro. Another aphorism therefore arose about vitamins—B vitamins are (parts of) coenzymes—an idea that was to be completely confirmed. 

Other organisms are equipped to produce ethanol, by employing a thiamine diphosphate-dependent decarboxylation of pyruvate to acetaldehyde (see Section 15.8) and NAD+ is regenerated by reducing the acetaldehyde to ethanol. This is a characteristic of baker s yeast, and forms the essential process for both bread making (production of CO2) and the brewing industry (formation of ethanol). 

Initially, pyruvate dehydrogenase [El] catalyzes the decarboxylation of pyruvate and the transfer of the resulting hydroxyethyl residue to thiamine diphosphate (TPP, la). The same enzyme then catalyzes oxidation of the TPP-bound hydroxyethyl group to yield an acetyl residue. This residue and the reducing equivalents obtained are then transferred to lipoamide (1b). 

A The main entry point for the TCA cycle is through generation of acetyl CoA by oxidative decarboxylation of pyruvate. 

Reddy et al. (1983) concluded that NO inactivation of iron-sulfur proteins was the probable mechanism of botulinal inhibition in nitrite-tteated foods. In support of this conclusion, Carpenter et al. (1987) observed decreased activity of clostridial pyruvate-ferredoxin oxidoteductase and lower cytochrome c reducing ability by ferredoxin in extracts of cells treated with nitrite. NO tteatment also inhibits yeast pyruvate decarboxylase (a non-iron-sulfur protein) and py-ruvate-ferredoxin oxidoteductase from C. perfringens (McMindes and Siedler, 1988). They suggested that thiamine-dependent decarboxylation of pyruvate may be an additional site for antimicrobial effects of NO. 

CpPNO in carbohydrate metabolism is not yet known, a Nar/-like hydroge-nase has been identified in both C. parvum (Stejskal et al. 2003 Abrahamsen et al. 2004) and C. hominis (Xu et al. 2004), which may function to oxidize the NADPH produced by PNO during pyruvate decarboxylation. Unlike other amitochondriate protists (Entamoeba, Giardia, Trichomonas), neither of these Cryptosporidia possesses an [FeFe]-hydrogenase capable of transferring electrons produced during the oxidation of PFO (Horner et al. 2000). It is proposed that the acetyl-CoA resulting from the decarboxylation of pyruvate in C. parvum may then be converted to malonyl-CoA (Templeton et al. 

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