Methylcrotonyl-CoA carboxylase

  • CAS Number: 9023-95-4
  • OMIM: 609 014
  • UniProt: Q9HCC0
  • CAS Number: 9023-95-4

The Methylcrotonoyl -CoA carboxylase is an enzyme that belongs to the class of ligases and is found in the mitochondria of animals and plants as well as in bacteria. Other names are methylcrotonyl -CoA carboxylase or abbreviated MCCase or MCC. CoA stands for coenzyme A.

The Methylcrotonoyl -CoA carboxylase makes the amino acid leucine for the energy supply of the organism used. Leucine is an essential nutrient for muscle, especially under heavy load or in periods of fasting. The enzyme requires the vitamin biotin to function. A defect in one of the two subunits results in a rare metabolic disorder.

Structure

The Methylcrotonoyl -CoA carboxylase is a heteromer, that consists of two different subunits. The larger α - subunit contains the biotin prosthetic group and is home to the docking site for adenosine triphosphate ( ATP ) and the domain is carboxylated to the biotin. The smaller β subunit contains the domain to which the carboxyl group is transferred from the biotin on the substrate.

Function

The Methylcrotonoyl -CoA carboxylase catalyzes the fourth reaction step in the degradation of the amino acid leucine to the versatile usable metabolic intermediates acetyl- CoA and acetoacetate. Here, a carboxyl group is bound to 3- Methylcrotonoyl - CoA consumption of a molecule ATP and there is 3- methylglutaconyl -CoA. The carboxyl group of biotin is transmitted, which is covalently linked to the rest of the protein of the amino acid lysine. How can to a long arm biotin between the two active sites of the enzyme swing back and forth. At the active site of the α - subunit biotin is carboxylated with ATP consumption, the second active site, which is located in the β - subunit, the carboxy group is transferred to the substrate. This mechanism is also found in the other dependent biotin carboxylases, such as pyruvate carboxylase, the propionyl -CoA carboxylase, and the acetyl-CoA carboxylase.

Regulation

The knowledge about the control of the Methylcrotonoyl -CoA Carboxlase by the organism is still very fragmentary, but it is certain that there are certain dependencies and regulatory mechanisms. The following examples are intended to give a short overview.

Gene expression

  • In human cells in the cell cycle in vitro an increase in gene transcription as well as the

Enzyme activity of Methylcrotonoyl -CoA carboxylase was measured.

  • In healthy subjects increased with biotin excess transcription of the gene for the α - subunit by a multiple. Under moderate biotin deficiency it decreases slightly, although stronger biotin deficiency does not lead to a decrease in the in vitro transcription. The authors of both articles conclude that the results strongly depend compared with thematically similar works of their own work groups and other groups of the experimental conditions. The presence of opposing regulatory mechanisms is discussed.
  • Arabidopsis plants ( Arabidopsis thaliana ) respond to a state of hunger caused by deprivation of the lighting or CO2, with increased expression of the genes of the two subunits of Methylcrotonoyl -CoA carboxylase. A biotin deficiency suppresses the increase of gene transcription in the fasting state.

Biotinylation of the enzyme

Tomato plant tissue depends on the activity of the control Methylcrotonoyl -CoA carboxylase through the biotinylation of the enzyme. (If biotin is bound to the α subunit, the enzyme is inactive. ) In roots and leaves, there were approximately equal amounts of the α - subunit, however, the enzyme activity in the leaves corresponded to 10 % of the activity in the roots. Although in the leaves free biotin is abundant, it was shown that this difference is due to a lower biotinylation of the α - subunit of the enzyme in the leaf tissue.

Genetics

The gene for the α - subunit encoded on human chromosome 3 in the q27.1 region, while the gene for the β - subunit in the region on chromosome 5 q12 - q13 is found.

A defect in one of the two subunits results in a rare metabolic disorder called Methylcrotonoyl -CoA carboxylase. Normally, the inheritance takes place autosomal recessive, but there are also cases with dominant defect known. Remains largely unresolved is the relationship between genotype and phenotype, so why two people with the same genetic defect ill vary in severity.

Human Genome Organisation CAS registry number Carboxylation Acetyl-CoA-Carboxylase Recessive trait Dominance (genetics)
559956
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