Decarboxylase biotin-dependent

Figure 1.34 Mechanism of decarboxylase-biotin-dependent catalyzed glutaconyl-CoA decarboxylation.

Biotin-dependent decarboxylases act as sodium ion pumps in Klebsiella74 and in various anaerobes.22 75 For example, oxaloacetate is converted to pyruvate and bound carboxybiotin.74 743 The latter is decarboxylated... 

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). 

In the bacterial biotin-dependent decarboxylases, reaction 2 proceeds from right to left, followed by decomposition of the carboxy-biotin to biotin and CO2. 

To allow estimation of human biotin requirements and evaluation of potential deleterious efiects of marginal degrees of biotin deficiency, indicators of biotin status need to be determined and validated. Several explored directions include serum concentrations and urinary excretion rates of biotin and biotin metabolites, activities of the biotin-dependent decarboxylases in peripheral blood mononuclear cells, and urinary excretion rates of 3-hydroxy-isovaleric acid 3-methylcrotonyl glycine and 2-methylcitric acid. 

The biotin-dependent enzyme group includes three classes of enzymes carboxylases, transcarboxylase, and decarboxylases (41). In all the reactions catalyzed by these enzymes, biotin acts as a CO2 carrier via A i-carboxybiotin (Fig. 8). The reaction mechanism of biotin-dependent enzymes has been reviewed (42), as has their evolutionary relatedness (43). 

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... 

To clarify the characteristics of AMDase, the effects of additives were examined. The addition of ATP and coenzyme A (CoA) to the enzyme reaction mixture did not enhance the rate of decarboxylation. In the case of malonyl-CoA decarboxylase, ATP and substrate form a mixed anhydride, which in turn reacts with CoA to form a thiol ester of the substrate. In the case of AMDase, however, neither ATP nor CoA had any effect, so this mechanism is unlikely. It is well established that avidin is a potent inhibitor of biotin-enzyme complex formation [11,12]. In this case, addition of avidin had no influence on decarboxylase activity, indicating that AMDase is not a biotin-dependent decarboxylase. Thus, the cofactor requirements of AMDase are entirely different from known analogous enzymes, such as malonyl-CoA decarboxylases. 

R. L. Baxter, and L. Sawyer. Biotin synthesis requires three other enzymes (steps b, c, d). Step b is catalyzed by a PLP-dependent transaminase. At the left is thiamin diphosphate, in the form of its 2-(1 -hydroxyethyl) derivative, an intermediate in the enzyme pyruvate decarboxylase (Dobritzsch et al.,. Biol. Chem. 273,20196-20204,1998). Courtesy of Guoguang Lu. Thiamin diphosphate functions in all living organisms to cleave C-C bonds adjacent to C=O groups. 

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