A-methylacyl-CoA racemase

Schmitz, W., Fingerhut, R. Conzelmann, E. 199A) Eur. J. Biochem. 222, 313-323. Purification and properties of an a-methylacyl-CoA racemase from rat liver. 

Schmitz, W., Helander, H.M., Hiltunen, J.K.. Conzelmann, E. (1997) Biochem. J. 326, 883 89. Molecular cloning of cDNA species for rat and mouse liver a-methylacyl-CoA racemases... 

Ferdinandusse, S. Overmars, H. Denis, S. Waterham, H.R. Wanders, R.J. Vreken, P. Plasma analysis of di- and trihydroxycholestanoic acid diastereomers in peroxisomal a-methylacyl-CoA racemase deficiency. J. Lipid Res. 2001, 42 (1), 137-141. 

The painkiller ibuprofen, commonly available under the names Advil and Motrin, is sold as a racemate. Even though the active ingredient is the (5)-(+) enantiomer ( dexibuprofen ), the racemate is almost as active as the (S) form. As luck (for the discoverers) would have it (see also Problem 64), an enzyme in the body, a-methylacyl-CoA racemase, converts the inactive (R) to the (S) isomer to the tune of 63%, thus adding value to the racemic mixture. 

Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, Mclean BN, Brown AY, Vreken P, Waterham HR, Wanders RJA (2000) Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet 24 188-191... 

Luo J, Zha S, Gage WR, Dunn TA, Hicks JL, Bennett CJ, Ewing CM, Platz EA, Ferdinandusse S, Wanders RJ, Trent JM, Isaacs WB, De Marzo AM. Alpha-methylacyl-CoA racemase a new molecular marker for prostate cancer. Cancer Res 2002 62 2220-2226. 

Strater J, Wiesmuller C, Perner S, et al. Alpha-methylacyl-CoA racemase (AMACR) immunohistochemistry in Barrett s and colorectal mucosa only significant overexpression favours a diagnosis of intraepithelial neoplasia. Histopathology. 2008 52 399-402. 

Jiang Z, Wu CL, Woda BA, et al. P504S/alpha-methylacyl-CoA racemase a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy. Am J Surg Pathol. 2002 26 1169. 

Also other members of the profen-family, among them naproxen, flurbiprofen, ketoprofen and tiaprofenic acid, are of great importance today. In general, these are 2-aryl- or 2-heteroaryl-propionic acids, of which in vitro only the (S)-(+)-enantiomer inhibits cyclooxygenase-1 (Fig. 5.84). In vivo, depending on the particular animal species, and also in humans, the (U)-(-)-enantiomer is converted to various degrees into its (S)-enantiomer with the aid of -methylacyl-CoA-racemase, via the Coenzyme A-thioester. In addition, more recent investigations could show that (R)-ibuprofen and (R)-flurbiprofen themselves have also anti-inflammatory properties. Many of the profens, with the exception of naproxen, are therefore marketed as racemates. 

Van Veldhoven, P.P., Croes, K., Casteels, M. Mannaerts, G.P. (1997) Biochim. Biophys. Ada. 1347, 62-68. 2-Methylacyl racemase a coupled assay based on the use of pristanoyl-CoA oxidase/peroxidase and reinvestigation of its subcellular istribution in rat and human liver. 

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