The methylcitrate cycle, or the MCC, is the mechanism by which propionyl-CoA is formed, generated by

β-oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, ...

of odd-chain fatty acids, and broken down to its final products, succinate and

pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic aci ...

. The methylcitrate cycle is closely related to both the citric acid cycle and the glyoxylate cycle, in that they share substrates, enzymes and products. The methylcitrate cycle functions overall to detoxify bacteria of toxic propionyl-CoA, and plays an essential role in propionate metabolism in bacteria. Incomplete propionyl-CoA metabolism may lead to the buildup of toxic metabolites in bacteria, and thus the function of the methylcitrate cycle is an important biological process.

History

2-methyl''iso''citric acid, an intermediate of the methylcitrate cycle, was first synthesized in 1886 as a mixture of four isomers. The pathway of the methylcitrate cycle was not discovered until 1973 in fungi, though it was not yet fully understood. Originally, the methylcitrate cycle was thought to be present only in fungal species, such as '' Candida lipolytica'' and '' Aspergillus nidulans''. In 1999, it was discovered that the methylcitrate cycle was also present in bacteria '' Salmonella enterica'' and '' Escherichia coli''. Much research has been done on the methylcitrate cycle's role in the development and function of various fungi and strains of bacteria, as well as its virulent properties in conjunction with the glyoxylate cycle.

Steps

There are three basic steps in the methylcitrate cycle, as outlined below. Additionally, the mechanism is shown with its reactants, products, intermediates, and enzymes. The major enzymes involved in this process are methylcitrate synthase (MCS) in step one, methylcitrate dehydratase (MCD) in step two, and 2-methyl''iso''citrate lyase (MCL) in step three. The PrpC gene, which encodes for enzyme methylcitrate synthase in the first step of the methylcitrate cycle, is the gene responsible for propionate metabolism in the process. Without this gene, the methylcitrate cycle and ultimate metabolism would not occur, but rather catabolism. The reaction of the methylcitrate cycle both overlaps and intertwines with the citric acid cycle and the glyoxylate cycle. Odd-chain fatty acids

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

and propionate are broken down by the β-oxidation cycle to form acetyl-CoA, which is further oxidized by the citric acid cycle, and propionyl-CoA, which is oxidized by the methylcitrate cycle. The substrate oxaloacetate is generated by the citric acid and glyoxylate cycles, and the product succinate is taken from the methylcitrate cycle to be used in the citric acid cycle.

Products

One of the major products of the methylcitrate cycle is pyruvate. This pyruvate can be used by metabolic enzymes for energy and biomass formation. The other major product, succinate, is used in the citric acid cycle and helps to carry the reaction forward and restarts the cycle. Succinate is used by the citric acid and glyoxylate cycles to generate oxaloacetate, one of the key substrates necessary to begin the methylcitrate cycle.

References

{{cite journal , last1=Lee , first1=SH , last2=Han , first2=YK , last3=Yun , first3=SH , last4=Lee , first4=YW , year=2009 , title=Roles of the Glyoxylate and Methylcitrate Cycles in Sexual Development and Virulence in the Cereal Pathogen ''Gibberella zeae'' , journal=Eukaryotic Cell , volume=8 , issue=8 , pages=1155–1164 , publisher=American Society for Microbiology , doi=10.1128/EC.00335-08 , pmid=19525419 , pmc=2725564 , s2cid=2150671 , url= Molecular biology