α‐Methylacyl‐CoA racemase – an ‘obscure’ metabolic enzyme takes centre stage

Abstract

Branched‐chain lipids are important components of the human diet and are used as drug molecules, e.g. ibuprofen. Owing to the presence of methyl groups on their carbon chains, they cannot be metabolized in mitochondria, and instead are processed and degraded in peroxisomes. Several different oxidative degradation pathways for these lipids are known, including α‐oxidation, β‐oxidation, and ω‐oxidation. Dietary branched‐chain lipids (especially phytanic acid) have attracted much attention in recent years, due to their link with prostate, breast, colon and other cancers as well as their role in neurological disease. A central role in all the metabolic pathways is played by α‐methylacyl‐CoA racemase (AMACR), which regulates metabolism of these lipids and drugs. AMACR catalyses the chiral inversion of a diverse number of 2‐methyl acids (as their CoA esters), and regulates the entry of branched‐chain lipids into the peroxisomal and mitochondrial β‐oxidation pathways. This review brings together advances in the different disciplines, and considers new research in both the metabolism of branched‐chain lipids and their role in cancer, with particular emphasis on the crucial role played by AMACR. These recent advances enable new preventative and treatment strategies for cancer.

The Challenges of a Successful Pregnancy in a Patient with Adult Refsum’s Disease due to Phytanoyl-CoA Hydroxylase Deficiency

“…Ibuprofen is generally avoided because it is metabolised by AMACR and may interfere with the metabolism of phytanic acid (Lloyd et al 2008). Most medications are safe as long as they do not contain animal fat but even if these contain phytanic acid then the additional exposure is likely to be small.…”

Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism

“…On the other hand, in many cancers, enzymes acting on branched substrates are upregulated. A remarkable example is the overexpression of AMACR in prostate cancer and different other neoplasms ( 96,228 ). Also, MFP2 and ACOX3 are upregulated in transformed tissues such as prostate and breast cancer ( 107 ).…”

Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers

“…8 AMACR levels and activity are associated with certain types of cancer (prostate, colon and others). 9 Today the chiral inversion of optically active NSAIDs by AMACR is considered as a novel mechanism of their anti-cancer activity; it is believed that the enzymatically activated conversion of NSAIDs blocks the other harmful effects of an entire group of enzymes (transferases). 8,[10][11][12][13][14][15] It is worth emphasizing that this activity of NSAIDs also shows high stereoselectivity.…”