Pyruvate decarboxylase, role

PDH is a multi-enzyme complex consisting of three separate enzyme units pyruvate decarboxylase, transacetylase and dihydrolipoyl dehydrogenase. Serine residues within the decarboxylase subunit are the target for a kinase which causes inhibition of the PDH the inhibition can be rescued by a phosphatase. The PDH kinase (PDH-K) is itself activated, and the phosphatase reciprocally inhibited, by NADH and acetyl-CoA. Figure 3.12(a and b) show the role and control of PDH. 

Pinhero, R. G., Copp, L. J., Amaya, C. -L., Marangoni, A. G., Yada, R. Y. (2007). Roles of Alcohol dehydrogenase. Lactate dehydrogenase and Pyruvate decarboxylase in Low Temperature Sweetening in a tolerant and susceptible varieties of Potato (Solanum tuberosum). Physiologia Plant, 130(2), 230-239. 

The combined dehydrogenation and decarboxylation of pyruvate to the acetyl group of acetyl-CoA (Fig. 16-2) requires the sequential action of three different enzymes and five different coenzymes or prosthetic groups—thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), coenzyme A (CoA, sometimes denoted CoA-SH, to emphasize the role of the —SH group), nicotinamide adenine dinucleotide (NAD), and lipoate. Four different vitamins required in human nutrition are vital components of this system thiamine (in TPP), riboflavin (in FAD), niacin (in NAD), and pantothenate (in CoA). We have already described the roles of FAD and NAD as electron carriers (Chapter 13), and we have encountered TPP as the coenzyme of pyruvate decarboxylase (see Fig. 14-13). 

EC 1.11.1.7) (68) and diphenol oxidase (EC 1.10.3.1) (69) have been identified. The potential role of pyruvic decarboxylase (EC 4.1.1.1) catalyzed reaction as a source of acetaldehyde and other aldehydes in juice was discussed (70). Raymond et al. (71) isolated the decarboxylase from orange juice sections and demonstrated that only 10 to 15% of the enzyme was in an active form. Since the purified enzyme was only active with pyruvic acid and 2-ketobutyric acid of the series of 2-ketoacids examined, they (71) concluded that the direct contribution of orange pyruvic decarboxylase to the orange volatile profile was limited to acetaldehyde and possibly propionaldehyde. 

The identity of the enzyme(s) involved in the latter reaction has been debated (13). However, the formation of the above hydro-xyketone, in analogy with acetoin, has been conceptualized as the consequence of the condensation of the "active" form of acetaldehyde, that is formed by decarboxylative addition of pyruvate to thiamine pyrophospate, with benzaldehyde.The role of pyruvate, in fact has been established. The same mechanism can be invoked for the reaction of cinnamaldehyde.lt is known that the pyruvate decarboxylase (E.C. 4.1.1.1) accepts as substrates a-oxoacids... 

In order to further characterize the key role of the 4 -amino group of ThDP for cofactor activation, the influence of the chemical environment at the active site of pyruvate decarboxylase from Zymomonas mobilis on the electronic properties of the 4 -amino group was studied by two-dimensional proton-nitrogen correlated NMR spectroscopy (Tittmann et al., 2005a). Chemical shift analysis and its pH dependence indicate that the acceleration of C2 deprotonation by 5 orders of magnitude is not mainly of thermodynamic nature caused by a significant increase in basicity... 

Killenberg-Jabs, M., Konig, S., Eberhardt, 1., Hohmann, S., Hubner, G. (1997), Role of Glu51 for cofactor binding and catalytic activity in pyruvate decarboxylase from yeast studied by site-directed mutagenesis. Biochemistry 36, 1900—1905. 

Transketolase resembles pyruvate decarboxylase, the enzyme that converts pyruvate to acetaldehyde (Section 17.4), in that it also requires Mg and thiamine pyrophosphate (TPP). As in the pyruvate decarboxylase reaction, a carb-anion plays a crucial role in the reaction mechanism, which is similar to that of the conversion of pyruvate to acetaldehyde. 

In addition to its role in the action of pyruvate dehydrogenase, thiamine pyrophosphate (TPP) serves as a cofactor for other enzymes, such as pyruvate decarboxylase, which catalyzes the nonoxidative decarboxylation of pyruvate. Propose a mechanism for the reaction catalyzed by pyruvate decarboxylase. What product would you expect Why, in contrast to pyruvate dehydrogenase, are lipoamide and FAD not needed as cofactors for pyruvate decarboxylase ... 

Pyruvate decarboxylase is able to catalyze two different reactions the nonoxidative decarboxylation of a-keto acids to the corresponding aldehydes [10,15-17] and a car-boxyligase side reaction leading to the formation of hydroxy ketones [18,19]. An understanding of why the last reaction is catalyzed by pyruvate decarboxylase, the physiological role of which is to decarboxylate pyruvate to acetaldehyde, was revealed by the discovery that pyruvate decarboxylase is homologous with acetolactate synthase [20], the enzyme catalyzing an acyloin condensation in the first step of isoleucine-valine biosynthesis. 

Pyruvate decarboxylase (PDase, EC 4.1.1.1), which catalyzes the reaction as shown in Eq. (17), has been studied since the early twentieth century as one of the key enzymes working in glycolysis [31-33]. It has l n isolated from yeast [34], wheat germ [35], sweet potato [36], and a wide variety of other sources. Recently, this enzyme was revealed to also play an important role in nonmevalonate pathway for terpenoid biosynthesis [37]. 

Pyruvate carboxylase is a mitochondrial enzyme and like other carboxylase or decarboxylase enzymes requires biotin as coenzyme. The biotin is firmly attached to the enzyme protein (i.e. a prosthetic group) via a lysine residue. The role of biotin is to hold the C02 in the correct orientation to allow its incorporation into the pyruvate. 

Pyruvoyl cofactor is derived from the posttranslational modification of an internal amino acid residue, and it does not equilibrate with exogenous pyruvate. Enzymes that possess this cofactor play an important role in the metabolism of biologically important amines from bacterial and eukaryotic sources. These enzymes include aspartate decarboxylase, arginine decarboxylase," phosphatidylserine decarboxylase, . S-adenosylmethionine decarboxylase, histidine decarboxylase, glycine reductase, and proline reductase. ... 

Two enzymes that contain the pyruvoyl cofactor are not decarboxylases D-proline reductase and glycine reductase. These enzymes were originally reported to contain the pyruvate in an ester linkage, but later studies have demonstrated its presence at the N-terminus of one of the subunits linked by the peptide amide bond. In contrast to the pynivoyl-dependent decarboxylases, the site of internal cleavage and modification of these reductases is a cysteine rather than a serine. The mechanism of post-translational biosynthesis of the pyruvoyl cofactor in these enzymes could conceivably proceed through the same mechanism shown in Scheme 1 but with the cysteine sulfur performing the role of the serine oxygen. 

One important subgroup of the lyases are the decarboxylases. The decarboxylation of amino acids is assisted by pyridoxal phosphate as a prosthetic group, whereas in the decarboxylation of pyruvate to acetaldehyde, thiamine pyrophosphate (TPP) plays that role. Oxidative decarboxylation, lastly, depends on the cooperation of no fewer than five cofactors thiamine pyrophosphate, lipoic acid, coenzyme A, flavin-adenine dinucleotide, and nicotinamide-adenine dinucleotide. 

Thiamine Vitamin Bi) is one of the longest-known vitamins. Its chemical structure is somewhat complicated it contains two heterocyclic rings (a pyrimidine and a thiazol ring, formula in Chapt. VI-5) connected at a quaternary N atom. It can easily be converted to the dihydro form, but its catalytic function does not seem to be that of a redox sy.stem. Thiamine pyrophosphate is the coenzyme of decarboxylases and aldehyde transferases. It plays a key role in oxidative decarboxylation of pyruvate (in the breakdown of carbohydrate) and of a-keto glutarate (in the citrate cycle). Man s requirements of thiamine are calculated in conjunction with his caloric intake, since the demand for the coenzyme is apparently higher wth a high overall metabolic rate. 

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