Acyl-CoA carboxylase

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. 

To investigate the cofactor requirement and the characteristics of the enzyme, the effects of additives were examined using phenylmalonic acid as the representative substrate. The addition of ATP or ADP to the enzyme reaction mixtures, with or without coenzyme A, did not enhance the rate of reaction. From these results, it is concluded that these co-factors are not necessary for this decarboxylase. It is well estabhshed that avidin is a potent inhibitor of the bio-tin-enzyme complex [11 -14]. In the present case, addition of avidin has no influence on the decarboxylase activity, indicating that the AMDase is not a biotin enzyme. Thus, the co-factor requirements of AMDase are entirely different from those of known analogous enzymes, such as acyl-CoA carboxylases [15], methyhnalonyl-CoA decarboxylases [11] and transcarboxylases [15,16]. 

One ligand, NCI-65828, was found to inhibit AccD5 (an essential acyl-CoA carboxylase carboxyltransferase domain) competitively with an experimental K of 13.1 pM... 

Lin TW, Melgar MM, Kurth D et al (2006) Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltrans-ferase domain of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 103 3072-3077... 

Propionate formation in cestodes probably proceeds essentially via reversal of the reactions required for the conversion of propionate to succinate in animal tissues (Fig. 5.10). Two of the enzymes involved, propionyl-CoA carboxylase and methylmalonyl-CoA mutase have been demonstrated in the mitochondria of S. mansonoides (643, 884). An acyl-CoA carboxylase, which can catalyse the carboxylation of propionyl-CoA, has also been isolated from this worm (533). The proposed pathway of propionate formation is associated with net ATP synthesis... 

Meyer, H., Mueller, J. Meyer, F. (1978). Isolation of an acyl-CoA carboxylase from the tapeworm Spirometra mansonoides. Biochemical and Biophysical Research Communications, 82 834-9. 

Diacovich L, Mitchell DL, Pham H, Gago G, Melgar MM, 27. Khosla C, Gramajo H, Tsai S-C. Crystal structure of the ji-subunit of acyl-coa carboxylase structure-based engineering of substrate specificity. Biochemistry 2004 43 14027-14036. 28. 

Gande R, Gibson KJC, Brown AK, Krumbach K, Dover LG, Sahm H, et al. Acyl-CoA carboxylases accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycohc acid biosynthesis in Corynebacteriaceae such as Corynebacterium glutamicum and Mycobacterium tuberculosis.J Biol Chem 2004 279 44847-57. 

The dtt/ 7-disrupted strain shows auxotrophy for oleic add and its ester (Tween 80). It can produce glutamate in the presence of excess biotin (Kimura et aL 1997) and exhibits decreased ODHC activity compared with the wild-type strain. Moreover, the intracellular level of DtsRl is decreased by biotin limitation and Tween 40 addition, but is not changed by penicillin addition (Kimura et aL 1999). These results suggest that the target of biotin limitation and Tween 40 treatment is the acyl-CoA carboxylase complex, including DtsRl, and these treatments seem to inhibit fatty acid biosynthesis in C. glutamicum. 

Acyl-CoA carboxylase pathways 3-hydroxypropionate/malonyl-CoA cycle [18, 19], 3-hydroxypropionate/4-hydroxybutyrate cycle [20], diearboxylate/ 4-hydroxybutyrate pathway [21], and the ethylmalonyl-CoA pathway [22]. 

To a further characterization of this enzyme, the effects of some additives were examined [16]. Addition of ATP or CoA-SH to the reaction mixture did not enhance the rate, in contrast to the case of malonyl-CoA decarboxylase and other decarboxylases reported so far, where substrate forms a thiol ester with Co-A with the assistance of ATP. More surprisingly, this enzyme was not a biotin enzyme, judging from the fact that there was no influence on the rate by the addition of avidin, a potent inhibitor of the biotin-enzyme complexes [17-20]. The cofactor requirements of AMDase are entirely different from those of known analogous enzymes, such as acyl-CoA carboxylases [21], methyl-malonyl-CoA decarboxylases [17], and transcarboxylases [21,22]. 

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