Methylmalonyl-CoA decarboxylase

Thus, AMDase requires no cofactors and this fact is entirely different from those of known analogous enzymes, such as acyl-CoA carboxylases, methylmalonyl-CoA decarboxylases " and transcarboxylases. 

PROPIONYL-CoA CARBOXYLASE METHYLMALONYL-CoA DECARBOXYLASE METHYLMALONYL-CoA EPIMERASE d-METHYLMALONYL-CoA HYDROLASE... 

Oxaloacetate decarboxylase Methylmalonyl-CoA decarboxylase Glutaconyl-CoA decarboxylase... 

Fig. 4 A, B. Polyketide synthase substrate routes. Potential substrates have been boxed A enzymes performing one enzymatic conversion 1, acetyl-CoA synthetase (alternatively, 1 represents a two enzyme pathway, acetate kinase followed by acetylphosphotransferase) 2, acetyl-CoA carboxylase 3, mal-onyl-CoA decarboxylase 4, malonyl-CoA synthetase B enzymes performing one enzymatic conversion 1, propionyl-CoA synthetase (T, propionate kinase followed by propionylphosphotransferase) 2, propionyl-CoA carboxylase 3, methylmalonyl-CoA decarboxylase 4, methylmalonyl-CoA epimerase 5, methylmalonyl-CoA mutase 6, isobutyryl-CoA mutase...

Decarboxylases. Pour decarboxylases, methylmalonyl-CoA decarboxylase, oxaloacetate decarboxylase, glutaconyl-CoA decarboxylase, and malonate decarboxylase, are encountered in anaerobic procaryotes. These biotin-dependent enzymes do not require ATP, are membrane bound, and are coupled to sodium... 

Biotin (referred to as vitamin H in humans) is an essential cofactor for a number of enzymes that have diverse metabolic functions. Almost a dozen different enzymes use biotin. Among the most well-known are acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, urea carboxylase, methylmalonyl-CoA decarboxylase, and oxaloacetate decarboxylase. Biotin serves as a covalent bound CO2 carrier for reactions in which CO 2 is fixed into an acceptor by carboxylases. Then this carboxyl group in an independent reaction can be transferred from the acceptor substrate to a new acceptor substrate by transcarboxylases, or the carboxyl group can be removed as CO 2 by decarboxylases. 

A. Hoffmann, W. Hilpert and P. Dimroth, "The carboxyltransferase activity of the sodium-ion-translocating methylmalonyl-CoA decarboxylase of Veillonella alcalescens", European Journal of Biochemistry 179,645-650 (1989). 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

Both methylmalonic aciduria and propionyl-CoA decarboxylase deficiency are usually accompanied by severe ketosis, hypoglycemia, and hyperglycinemia. The cause of these conditions is not entirely clear. However, methylmalonyl-CoA, which accumulates in methylmalonic aciduria, is a known inhibitor of pyruvate carboxylase. Therefore, ketosis may develop because of impaired conversion of pyruvate to oxalo-acetate. 

Figure 17 Design of assays to evaluate decarboxylation of methylmalonyl-CoA catalyzed by DEBS 1-TE. It was anticipated that a decarboxylase activity would incorporate deuterium into the starter unit of propionyl lactone and that such labeling would be visible by GC-MS analysis. As decarboxylation has been reported in the presence of primers other than propionyl-CoA, assays I—III included n-hutyryl-CoA as a starter unit. Assay IV was designed to evaluate the possibility that -butyryl-CoA suppresses decarboxylation. GC-MS analysis gave no evidence for labeling of the side chain in any assay. Therefore, decarboxylation is not a significant reaction of KSt under these conditions.

The biotin-dependent decarboxylases of anerobic microorganisms are transmembrane proteins. In addition to their roles in the metabolism of ox-aloacetate, methylmalonyl CoA, and glutaconyl CoA, they serve as energy transducers. They transport 2 mol of sodium out of the cell for each mole of substrate decarboxylated. The resultant sodium gradient is then used for active transport of substrates by sodium cotranspoit systems, or maybe used to drive ATP synthesis in a similar manner to the proton gradient in mammalian mitochondria (Buckel, 2001). 

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

The uropygial gland of birds, which produces polymethylated fatty acids houses a carboxylase which forms malonyl CoA from acetyl CoA and methylmalonyl CoA from propionyl CoA. In addition, there is a decarboxylase, which splits malonyl CoA, drastically lowering its concentration. Thus, for the formation of fatty acids methylmalonyl CoA is preferred though the fatty acid synthase of the gland reacts much faster with, malonyl CoA than with methylmalonyl CoA (Fig. 84). 

The formation of branched chain fatty acids by the Type I FAS of the sebaceous (uropygial) glands of waterfowl has already been mentioned (section 3.2.2(b) and Table 3.8). These acids arise because of the use of methylmalonyl-CoA rather than malonyl-CoA which is rapidly destroyed by a very active malonyl-CoA decarboxylase. The utilization of methylmalonyl-CoA results in the formation of products such as 2,4,6-trimethyl lauric acid and 2,4,6,8-tetramethyl decanoic acid as major products. 

Malonyl-CoA decarboxylase (EC. 4.1.1.9) from uropygial gland only works on (5)-enan-tiomer of methylmalonyl-CoA (16) [5], while the (R) isomer remained intact. In addition, the protonation of the resulting intermediate occurred in an enantio face-selective manner, as revealed by the fact that the absolute configuration the product, 2-( H)-propionyl-CoA (17) was obtained in an experiment carried out in [Eq. (9)], was R. 

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