Oxidative decarboxylation, enzyme-catalysed

The lyases comprise enzyme class 4. They are enzymes cleaving C-C, C-0, C-N and other bonds by elimination, not by hydrolysis or oxidation. Lyases also catalyse addition to donble bonds. The types of reactions catalysed by lyases are decarboxylation (decarboxylase), hydration/dehydration (hydratase/dehydratase), ammonia addition/deamination (ammonia-lyase), cyanohydrin formation/cleavage (oxynitrilase),... 

Malic enzyme catalyses the NADP-dependent oxidative decarboxylation of malate to pyruvate and C02 with the production of NADP which is utilized for the synthesis of long chain saturated fatty acids from malonyl CoA. 

In aerobic environments, eukaryotes and many eubacteria oxidatively decarboxylate the 2-oxoacids via pyruvate and 2-oxoglutarate dehydrogenase complexes [36]. For comparison with the archaebacterial oxidoreductases, the catalytic mechanism of these complexes is also shown in Fig. 4. Three enzymic activities are involved, catalysed by three distinct enzymes a 2-oxoacid decarboxylase (El), a dihydrolipoyl acyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). Multiple copies of these three enzymes are found in each complex molecule, resulting in relative molecular masses in excess of 2x10 ... 

An elegant work is reported concerning the oxidation of 2-alkyl and 2-benzylthia-zolium salts, in the presence of a base, with the scope of finding a structural relationship for the thiamine-bound intermediate which intervene in the oxidative decarboxylation of a-ketoacids catalysed by thiamin diphosphate-dependent enzymes. 2-Alkyl and 2-benzylthiazolium salts, which are not electroactive, can be transformed into electroactive species by treatment with the base (trimethylsilyl)amide. Subsequent anodic oxidation affords the corresponding symmetrical dimers, by an EC mechanism (Scheme 72). As expected, the stabilizing effect of the substituents R, R at the a-carbon on the radical cation follows the order H < Me < OMe. When R is aryl, electron-donating p-substituents again enhance the enamine oxidation. 

The four acetic acid side chains are decarboxylated (by the enzyme uro gen decarboxylase) to methyl groups to give copro gen III, followed by the oxidative decarboxylation of the two propionic acid side chains on rings A and B to vinyl groups (via the enzyme copro gen oxidase) giving proto gen IX. Oxidation of proto gen IX to protoporphyrin IX is then accomplished by the enzyme proto gen oxidase, followed by iron insertion catalysed by a very similar enzyme called ferrochelataseF Both enzymes are bound to the inner mitochondrial membrane. 

In the R.c.c., two of the reactions of the TCA cycle are replaced by alternative reactions catalysed by non-TCA cycle enzymes (i) the citrate (si)-synthase (EC 4.1.3.7)-catalysed formation of citrate from ace-tyl-CoA and oxaloacetate is replaced by the ATP citrate (pro-3.S)-lyase (EC 4.1.3.8)-catalysed, ATP-dri-ven cleavage of citrate to acetyl-CoA and oxaloacetate (eq. 1 J, Fig.), and (ii) the a-ketoglutaiate dehydrogenase complex-catalysed oxidative decarboxylation of a-ketoglutarate to CO2 and succinyl-CoA is replaced by the a-ketoglutarate synthase (EC 1.2.73)-catalysed reductive carboxylation of succinyl CoA (eq. 2 O, Fig.), in which the reductant is reduced ferredoxin (Fd, ... 

Lipoic acid is a five-membered cyclic disulphide ring with a five-carbon carboxylic add chain. When reduced it provides a constrained dithiol centre. This disulphide-dithiol cofactor is covalently bound to one of the enzymes in a multienzyme complex which catalyses oxidative decarboxylation of a-keto acids. In the course of the reaction three forms of the prosthetic group participate the cyclic disulphide, the dithiol and a thio-ester of the dithiol form. 

Most of ThDP-dependent enzymes catalyse the processing of 2-keto acids such as pyruvate, branched-chain keto acids and ketoglutarate. Among them, pyruvate is processed by various ThDP-dependent enzymes (Figure 4.2). Its carbonyl group is attacked by the ThDP ylide, yielding a tetrahedral 2-(2-lactyl)-ThDP adduct. The reactions followed by decarboxylation can be roughly classified into oxidative or nonoxidative ones. 

Glycolysis, catalysed by cytoplasmic enzymes, can operate under aerobic and anaerobic conditions to produce pyruvate, but in the absence of oxygen this is reduced further to ethanol, plus CO2 (or to lactic acid if no decarboxylation occurs). Anaerobic respiration (or fermentation) produces only two ATP molecules per molecule of glucose respired contrast this with six ATPs (though some authors claim eight ATPs) produced during pyruvate formation under aerobic conditions. In the presence of oxygen, further utilization of pyruvate occurs within the mitochondria. Here, oxidative decarboxylation of pyruvate to acetyl co-enzyme A (acetyl CoA), followed by complete oxidation of the... 

The enantiomorph of this deuteroamine, prepared by decarboxylation of a-deuteroglutamate in water, does not exchange deuterium with the solvent, under the same conditions. (a-Deuteroglutamate is prepared by enzyme-catalysed racemisation of d- or L-glutamate in deuterium oxide). Additional support for the stereospecificity of enzyme-catalysed decarboxylation of amino acids comes from experiments in which tyrosine was decarboxylated in DgO to give R-a-... 

A brilliantly simple and largely satisfying solution [16] to the observations on lysine and cadaverine incorporation has been proposed. It is consistent in particular with the observed incorporation of lysine with distinction between C-2 and C-6, loss of nitrogen from C-2 but retention of the C-2 proton and it allows for normal incorporation of cadaverine 6.26). Central to the proposal is enzyme-catalysed decarboxylation of lysine (lysine decarboxylase) and oxidation of cadaverine (diamine oxidase) both involving pyridoxal phosphate as coenzyme. The proposed sequence involves orthodox pyridoxal-linked intermediates of which 625) and 6.27) are common to both enzyme-mediated reactions (Scheme 6.8). It is an important... 

Formation of acetyl-CoA takes place in the mitochondrial matrix and is catalysed by pyruvate dehydrogenase. This is a multienzyme complex containing three enzymes which together are responsible for the oxidative decarboxylation of the pyruvate. Although the overall reaction may be represented quite simply as follows ... 

Thiamin has a central role in energy-yielding metabolism, and especially the metabolism of carbohydrates. Thiamin diphosphate (also known as thiamin pyrophosphate see Figure 11.12) is the coenzyme for three multienzyme complexes that catalyse oxidative decarboxylation of the substrate linked to reduction of enzyme-bound lipoamide, and eventually reduction of NADto NADH ... 

The synthesis of NAD from tryptophan involves the non-enzymic cyclization of aminocarboxymuconic semialdehyde to quinolinic acid. The alternative metabolic fate of aminocarboxymuconic semialdehyde is decarboxylation, catalysed by picolinate carboxylase, leading to acetyl CoA and total oxidation. There is thus competition between an enzyme-catalysed reaction, which has hyperbolic, saturable kinetics, and a non-enzymic reaction, which has linear kinetics. At low rates of flux through the pathway, most metabolism will be by way of the enzyme-catalysed pathway, leading to oxidation. As the rate of formation of aminocarboxymuconic semialdehyde increases, and picolinate carboxylase becomes more or less saturated, so an increasing proportion will be available to undergo cyclization to quinolinic acid and onward metabolism to NAD. There is thus not a simple stoichiometric relationship between tryptophan and niacin, and the equivalence of the two coenzyme precursors will vary as the amount of tryptophan to be metabolized and the rate of metabolism vary. 

A widely distributed cytoplasmic enzyme which catalyses the oxidative decarboxylation of isocitrate to n-oxoglutarate, a reaction which is accompanied by the reduction of NADP tc NADPH. (A mitochondrial enzyme also exists which uses NAC as a cofactor.) Elevated serum levels are found in liver disease. Ii can be measured by following the reduction of NADP bj ultraviolet spectrophotometry. 

A single copper containing protein with a requirement for ascorbic acid—p-hydroxyphenylpyruvate oxidase—catalyses the simultaneous hydroxylation of the phenyl ring, migration of the aliphatic side chain to an adjacent position on the ring, and oxidative decarboxylation of the pyruvate fragment . The enzyme... 

Isocitrate dehydrogenase catalyses the synthesis of oxoglutarate from iso-citrate through an oxidation-decarboxylation process. Two isocitrate dehydrogenases are present in the cell. The overall reaction is identical for both enzymes ... 

In the metabolism of L-leucine, the isovaleryl-CoA produced by the oxidative decarboxylation step is further metabolized by a series of enzyme-catalysed steps to acetoacetate and acetyl-CoA and thence into the tricarboxylic acid cycle. Specific enzyme deficiencies at every stage of this metabolic pathway are known and are described in Section 10.3. In contrast, only one disorder of L-isoleucine metabolism subsequent to the oxidative decarboxylation step has been recognized (Section 10.4), and no disorders of the L-valine pathway from isobutyryl-CoA have been described. This may be due to their relative rarity but possibly also to greater difficulty in their detection. The metabolism of valine and leucine is, however, of particular interest in the organic acidurias, since both are major precursors of propionyl-CoA and methylmalonyl-CoA, defects in the metabolism of which lead to propionic acidaemia and methylmalonic aciduria (Chapter 11). 

The a-ketoacid-dependent enzymes are distinguished from other non-haem iron enzymes by their absolute requirement for an a-ketoacid cofactor as well as Fe(II) and O2 for activity. They catalyse two types of reaction (Table 2.3), hydroxyla-tion and oxidation. In both, the a-ketoglutarate is decarboxylated and one oxygen atom introduced into the succinate formed in the hydroxylases, the other oxygen atom is introduced into the substrate, while in the oxidases it is found in water, together with the cyclized product. In general these enzymes require one equivalent of Fe(II) an a-ketoacid, usually a-ketoglutarate and ascorbate. Examples of these enzymes include proline 4-hydroxylase, prolyl and lysyl hydroxylase, which... 

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