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- (2R)-2-methylacyl-CoA (2S)-2-methylacyl-CoA
In mammalian cells, the enzyme is responsible for converting (2R)-methylacyl-CoA esters to their (2S)-methylacyl-CoA epimers and known substrates include coenzyme A esters of pristanic acid (mostly derived from phytanic acid, a 3-methyl branched-chain fatty acid that is abundant in the diet) and bile acids derived from cholesterol. This transformation is required in order to degrade (2R)-methylacyl-CoA esters by β-oxidation, which requires the (2S) epimer. The enzyme is known to be localised in peroxisomes and mitochondria, both of which are known to β-oxidise 2-methylacyl-CoA esters.
This enzyme belongs to the family of isomerases, to be specific those racemases and epimerases acting on other compounds. The systematic name of this enzyme class is 2-methylacyl-CoA 2-epimerase. In vitro experiments with the human enzyme AMACR 1A show that both (2S)- and (2R)-methyldecanoyl-CoA esters are substrates and are converted by the enzyme with very similar efficiency. Prolonged incubation of either substrate with the enzyme establishes an equilibrium with both substrates/products present in a near 1:1 ratio. The mechanism of the enzyme requires removal of the α-proton of the 2-methylacyl-CoA to form a deprotonated intermediate [which is probably the enol or enolate followed by non-sterespecific reprotonation. Thus either epimer is converted into a near 1:1 mixture of both isomers upon full conversion of substrate.
As of late 2007, 7 These structures are of the Mycobacterium tuberculosis version of the enzyme, known as MCR.
Both decreased and increased levels of the enzyme in humans is linked with diseases.
Reduction of protein levels or activity results in the accumulation of (2R)-methyl fatty acids such as bile acids which results in neurological symptoms. The symptoms are similar to adult Refsum disease and usually appear in the late teens or early 20's.
AMACR deficiency has recently been discovered. The first documented case was in 2006. It is in a class of disorders called peroxisome biogenesis disorders (PBD) although it is quite different than other peroxisomal disorders and does not share classic Refsum disorder symptoms. It causes an accumulation of pristanic acid, DHCA and EHCA and to a lesser extent VLCFA and phytanic acid. "His condition would have been missed if they hadn't measured the pristanic acid concentration." 
It can cause mental impairment,confusion, learning difficulties and liver damage. It can be treated by dietary elimination of pristanic and phytanic acid from meats such as beef, lamb, chicken, and dairy products, however compliance to the diet is low due to dietary habits, and loss of weight.
Increased levels of AMACR protein and activity are associated with prostate cancer, and the enzyme is used widely as a biomarker (known in the cancer literature as P504S) in biopsy tissues. Around 10 different variants of human AMACR have been identified from prostate cancer tissues, which arise from alternative mRNA splicing. Some of these splice variants lack catalytic residues in the active site or have changes in the C-terminus which is required for dimerisation. Increased levels of AMACR are also associated with some breast, colon and other cancers but it is unclear exactly what the role of AMACR is in these cancers.
The enzyme is also involved in a chiral inversion pathway which converts ibuprofen, a member of the 2-arylpropionic acid (2-APA) of the non-steroidal anti-inflammatory drug family (NSAIDs) from the R-enantiomer to the S-enantiomer. The pathway is uni-directional because only R-ibuprofen can be converted into ibuprofenoyl-CoA, which is then epimerised by AMACR. Conversion of S-ibuprofenoyl-CoA to S-ibuprofen is assumed to be performed by one of the many human acyl-CoA thioesterase enzymes (ACOTs). The reaction is of pharmacological importance because ibuprofen is typically used as a racemic mixture, and the drug is converted to the S-isomer upon uptake, which inhibit the activity of the cyclo-oxygenase enzymes and hence bring about an anti-inflammatory effect. Recently human AMACR 1A has been demonstrated to epimerise other 2-APA-CoA esters, suggesting a common chiral inversion pathway for this class of drugs.