Oxoglutarate decarboxylase

Fig. 2. Mechanism of the oxidative decarboxylation of 2-oxoglutarate by the 2- oxoglutarate dehydrogenase complex EC 1.2.4.2). Enzyme, = 2-oxoglutarate decarboxylase. Enzym = lipoyl-redurtase-transacetylase (lipoyl reductase-t-transsuccinylase). Enzymej = dihydrolipoyl dehydrogenase, tpp-thiamin pyrophosphate. HSCoA = coenzyme A.

Oxoglutarate undergoes oxidative decarboxylation to succinyl-CoA, via multi-enzyme reaction similar to the reaction pattern of pyruvate. The multi-enzyme complex (mw about 2 x 10 ) is an octamer of an elementary unit containing each of the three contributing enzyme proteins oxoglutarate decarboxylase, dihydro-lipoyl transacetylase, and dihydrolipoyl dehydrogenase. The overall reaction involves thiamine pyrophosphate, lipoic acid, CoASH and NAD succinyl-CoA is the end product ... 

Tissues of the mammalian central nervous system contain a pyridoxal phosphate-dependent glutamate decarboxylase that catalyzes conversion of Glu to y-aminobutyrate (GABA), an inhibitory synaptic transmitter. GABA is degraded by trans-imination with a-oxoglutarate as the acceptor to yield succinic semialdehyde, which then is oxidized to succinate by an NAD-linked dehydrogenase. 

There are two 2-oxoacid dehydrogenase multienzyme complexes in E. coli. One is specific for pyruvate, the other for 2-oxoglutarate. Each complex is about the size of a ribosome, about 300 A across. The pyruvate dehydrogenase is composed of three types of polypeptide chains El, the pyruvate decarboxylase (an a2 dimer of Mr — 2 X 100 000) E2, lipoate acetyltransferase (Mr = 80 000) and E3, lipoamide dehydrogenase (an a2 dimer of Mr = 2 X 56 000). These catalyze the oxidative decarboxylation of pyruvate via reactions 1.6, 1.7, and 1.8. (The relevant chemistry of the reactions of thiamine pyrophosphate [TPP], hydroxyethylthiamine pyrophosphate [HETPPJ, and lipoic acid [lip-S2] is discussed in detail in Chapter 2, section C3.)... 

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

Figure 8.4. Pathways of tryptophan metaholism. Tryptophan dioxygenase, EC 1.13.11.11 formylkynurenine formamidase, EC 3.5.1.9 kynurenine hydroxylase, EC 1.14.13.9 kynureninase, EC 3.7.1.3 3-hydroxyanthranilate oxidase, EC 1.10.3.5 picolinate carboxylase, EC 4.1.1.45 kynurenine oxoglutarate aminotransferase, EC 2.6.1.7 kynurenine glyoxylate aminotransferase, 2.6.1.63 tryptophan hydroxylase, EC 1.14.16.4 and 5-hydroxytryptophan decarboxylase, EC 4.1.1.26. Relative molecular masses (Mr) tryptophan, 204.2 serotonin, 176.2 kynurenine, 208.2 3-hydroxykynurenine, 223.2 kynurenic acid, 189.2 xanthurenic acid, 205.2 and quinolinic acid 167.1. CoA, coenzyme A.

Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease The third oxo-add dehydrogenase catalyzes the oxidative decarboxylation of the branched-chain oxo-acids that arise from the transamination of the branched-chain amino acids, leucine, isoleuctne, emd vtdine. It has a similEU subunit composition to pyruvate and 2-oxoglutarate dehydrogenases, and the E3 subunit (dihydrolipoyl dehydrogenase) is the stune protein as in the other two multienzyme complexes. Genetic lack of this enzyme causes maple syrup urine disease, so-called because the bremched-chain oxo-acids that are excreted in the urine have a smell reminiscent of maple syrup. 

The biogenesis of solerone 1 and related compounds was successfully rationalized by biomimetic model reactions. As key step we established the pyruvate decarboxylase catalyzed acyloin condensation of pyruvic acid with ethyl 4-oxobutanoate 4 or ethyl 2-oxoglutarate 3 with acetaldehyde. The importance of the ethyl ester function in 3 and 4 serving as substrates for the enzymatic formation of a-hydroxy ketones 5 and 6 was demonstrated. The identification of six yet unknown sherry compounds including acyloins 5 and 6, which have been synthesized for the first time, confirmed the relevance of the biosynthetic pathway. Application of MDGC-MS allowed the enantiodifferentiation of a-ketols and related lactones in complex sherry samples and disclosed details of their biogenetic relationship. 

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 ... 

H]pyridoxamine which was converted by aspartate aminotransferase apoca-zyme in the presence of a-oxoglutarate into pyridoxal with retention of H. A knowledge of the stereochemical course of the latter reaction which removes the C-4 Hgi atom allowed the conclusion that the [4 - H]pyridoxamine had the (R) configuration (Fig. 48). The reduction by NaB H4 must have involved [101] attack on the Re face of the w-electron system at C-4 of the species (Fig. 48, 1). The conclusion for aspartate aminotransferase has recently been confirmed by Zito and Martinez-Carrion [93] and the same approach when applied to tyrosine decarboxylase [103], also showed the hydride attack to occur on the Re face at C-4 of the coenzyme-enzyme imine bond. In both cases, therefore, the Re face at C-4 must be exposed to the solvent side in the binary complex. 

Fig. 20.3 Pathway of methionine metabolism. The numbers represent the following enzymes or sequences (1) methionine adenosyltransferase (2) S-adenosylmethionine-dependent transmethylation reactions (3) glycine methyltransferase (4) S-adenosylhomocysteine hydrolase (5) betaine-homocysteine methyltransferase (6) 5-methyltetrahydrofolate homocysteine methyltransferase (7) serine hydroxymethyltransferase (8) 5,10-methylenetetrahydrofolate reductase (9) S-adenosylmethionine decarboxylase (10) spermidine and spermine synthases (11) methylthio-adenosine phosphorylase (12) conversion of methylthioribose to methionine (13) cystathionine P-synthase (14) cystathionine y-lyase (15) cysteine dioxygenase (16) cysteine suplhinate decarboxylase (17) hypotaurine NAD oxidoreductase (18) cysteine sulphintite a-oxoglutarate aminotransferase (19) sulfine oxidase. MeCbl = methylcobalamin PLP = pyridoxal phosphate...

Collins G G S (1972) GABA-2-oxoglutarate transaminase, glutamate decarboxylase, and the half-life of GABA m different areas of rat brain. Biochem Pharmacol 21, 2849-2853. 

In the same scheme, a representation of the action of tyrosine transaminase (EC 2.6.1.5) acting on tyrosine (Tyr, Y) is shown. This enzyme utilizes pyridoxal phosphate to remove toe amino group from tyrosine (Tyr, Y) and transfer it to a-ketoglutarate (2-oxoglutarate) with formation of glutamate (Glu, E) from the latter and 4-hydroxyphenylpyruvate from the former. Then, 4-hydroxyphenylpyruvate decarboxylase (EC 4.1.1.80), which appears to require thiamine diphosphate and... 

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