Disease relevance of MCEE

• Energy expenditures were measured in 20 patients by indirect calorimetry (MEE) and estimated initially by the Curreri formula (CEE) and subsequently by a modification of the Curreri formula (MCEE), adjusted for changes in open wound size and body weight [1].
• RESULTS: The crystal structure of MMCE from Propionibacterium shermanii has been determined at 2.0 A resolution [2].

High impact information on MCEE

• In this report, we identify the human DL-methylmalonyl-CoA racemase gene by analyzing prokaryotic gene arrangements and extrapolating the information obtained to human genes by homology searches [3].
• The known types of reactions that are catalyzed include isomerizations (glyoxalase I), epimerizations (methylmalonyl-CoA epimerase), oxidative cleavage of C-C bonds (extradiol dioxygenase), and nucleophilic substitutions (fosfomycin resistance proteins) [4].
• The C. elegans mce-1 deletion mutant demonstrates for the first time that a lesion at the epimerase step of methylmalonyl-CoA metabolism can functionally impair flux through the methylmalonyl-CoA mutase pathway and suggests that malfunction of MCEE may cause methylmalonic acidemia in humans [5].
• To assess the impact of isolated MCE deficiency in cultured cells, HeLa cells were transfected with a selectable vector containing MCEE-specific small interfering RNA (siRNA) to suppress gene expression [6].
• Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: Evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism [5].

Associations of MCEE with chemical compounds

• When [methyl-3H]methylmalonyl-CoA was incubated with highly purified methylmalonyl-CoA mutase, tritium exchange with the medium depended on added methylmalonyl-CoA epimerase [7].
• With highly purified preparations of methylmalonyl-CoA mutase, effective tritium exchange from [5'-3H]adenosylcobalamin to water required the addition of methylmalonyl-CoA epimerase and of substrate (e.g. succinyl-CoA) [7].
• Because little is known about mammalian DL-methylmalonyl-CoA racemase and because it is involved in the flow of D-methylmalonyl-CoA to L-methylmalonyl-CoA----tricarboxylic acid cycle (versus to methylmalonic acid), we developed a new assay and purified rat liver racemase 23,000-fold to homogeneity [8].
• The metal binding residues also align precisely, and striking structural similarities between MMCE and glyoxalase I suggest common mechanisms in their respective epimerization and isomerization reactions [2].
• BACKGROUND: Methylmalonyl-CoA epimerase (MMCE) is an essential enzyme in the breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine, and methionine [2].

Analytical, diagnostic and therapeutic context of MCEE

• The patient was found to be homozygous for a c.139C>T (p.R47X) mutation in MCEE by sequence analysis that was confirmed by restriction digestion of PCR products [6].
• HPLC assay for methylmalonyl-CoA epimerase [9].

References