AMACR
Alpha-methylacyl-CoA racemase, also known as AMACR, is a protein which in humans is encoded by the AMACR gene.[1][2]
Function
The AMACR protein helps to metabolize certain fatty acids within the body.
Clinical significance
Several studies have suggested that AMACR can be used as a prostate cancer biomarker.[3]
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." [4]
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.[5][6]
References
- ^ "Entrez Gene: AMACR alpha-methylacyl-CoA racemase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23600.
- ^ Schmitz W, Helander HM, Hiltunen JK, Conzelmann E (September 1997). "Molecular cloning of cDNA species for rat and mouse liver alpha-methylacyl-CoA racemases". Biochem. J.. 326 ( Pt 3): 883–9. PMC 1218746. PMID 9307041. http://www.biochemj.org/bj/326/0883/bj3260883.htm.
- ^ Rubin MA, Bismar TA, Andrén O, Mucci L, Kim R, Shen R, Ghosh D, Wei JT, Chinnaiyan AM, Adami HO, Kantoff PW, Johansson JE (June 2005). "Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death". Cancer Epidemiol. Biomarkers Prev. 14 (6): 1424–32. doi:10.1158/1055-9965.EPI-04-0801. PMID 15941951.
- ^ McLean BN, Allen J, Ferdinandusse S, Wanders RJ (March 2002). "A new defect of peroxisomal function involving pristanic acid: a case report". J. Neurol. Neurosurg. Psychiatr. 72 (3): 396–9. doi:10.1136/jnnp.72.3.396. PMC 1737782. PMID 11861706. http://www.repository.naturalis.nl/document/33804.
- ^ Chedrawi A, Clark GD (2007-03-08). "Peroxisomal Disorders: Overview - eMedicine Neurology". medscape.com. http://emedicine.medscape.com/article/1177387-overview. Retrieved 2009-03-16.
- ^ Wanders RJA, Waterham HR, Leroy BP (2006-03-20). "Refsum Disease". GeneReviews -- NCBI Bookshelf. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=refsum. Retrieved 2009-03-16.
Further reading
- Jiang Z, Woda BA, Wu CL, Yang XJ (2004). "Discovery and clinical application of a novel prostate cancer marker: alpha-methylacyl CoA racemase (P504S).". Am. J. Clin. Pathol. 122 (2): 275–89. doi:10.1309/EJUY-UQPE-X1MG-68MK. PMID 15323145.
- Bautch S (1991). "Wisconsin doctor selected as national symbol of physicians' sacrifices.". Wis. Med. J. 90 (8): 485–7. PMID 1926890.
- Schmitz W, Albers C, Fingerhut R, Conzelmann E (1995). "Purification and characterization of an alpha-methylacyl-CoA racemase from human liver.". Eur. J. Biochem. 231 (3): 815–22. doi:10.1111/j.1432-1033.1995.tb20766.x. PMID 7649182.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Schmitz W, Helander HM, Hiltunen JK, Conzelmann E (1997). "Molecular cloning of cDNA species for rat and mouse liver alpha-methylacyl-CoA racemases.". Biochem. J.. 326 ( Pt 3): 883–9. PMC 1218746. PMID 9307041. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1218746.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Ferdinandusse S, Denis S, Clayton PT, et al. (2000). "Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy.". Nat. Genet. 24 (2): 188–91. doi:10.1038/72861. PMID 10655068.
- Kotti TJ, Savolainen K, Helander HM, et al. (2000). "In mouse alpha -methylacyl-CoA racemase, the same gene product is simultaneously located in mitochondria and peroxisomes.". J. Biol. Chem. 275 (27): 20887–95. doi:10.1074/jbc.M002067200. PMID 10770938.
- Amery L, Fransen M, De Nys K, et al. (2001). "Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans.". J. Lipid Res. 41 (11): 1752–9. PMID 11060344.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Rubin MA, Zhou M, Dhanasekaran SM, et al. (2002). "alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer.". JAMA 287 (13): 1662–70. doi:10.1001/jama.287.13.1662. PMID 11926890.
- Luo J, Zha S, Gage WR, et al. (2002). "Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer.". Cancer Res. 62 (8): 2220–6. PMID 11956072.
- Zhou M, Chinnaiyan AM, Kleer CG, et al. (2002). "Alpha-Methylacyl-CoA racemase: a novel tumor marker over-expressed in several human cancers and their precursor lesions.". Am. J. Surg. Pathol. 26 (7): 926–31. doi:10.1097/00000478-200207000-00012. PMID 12131161.
- Kuefer R, Varambally S, Zhou M, et al. (2002). "alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation.". Am. J. Pathol. 161 (3): 841–8. doi:10.1016/S0002-9440(10)64244-7. PMC 1867250. PMID 12213712. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1867250.
- Varambally S, Dhanasekaran SM, Zhou M, et al. (2002). "The polycomb group protein EZH2 is involved in progression of prostate cancer.". Nature 419 (6907): 624–9. doi:10.1038/nature01075. PMID 12374981.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Leav I, McNeal JE, Ho SM, Jiang Z (2003). "Alpha-methylacyl-CoA racemase (P504S) expression in evolving carcinomas within benign prostatic hyperplasia and in cancers of the transition zone.". Hum. Pathol. 34 (3): 228–33. doi:10.1053/hupa.2003.42. PMID 12673556.
- Shen-Ong GL, Feng Y, Troyer DA (2003). "Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with fumarate hydratase homology.". Cancer Res. 63 (12): 3296–301. PMID 12810662.
- Zha S, Ferdinandusse S, Denis S, et al. (2004). "Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer.". Cancer Res. 63 (21): 7365–76. PMID 14612535.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
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| Enzymes |
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| Transporters |
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| Structure/Peroxin |
PEX1, PEX2 - PXMP3, PEX3, PEX5, PEX6, PEX7, PEX10, PEX11A, PEX11B, PEX11G, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26
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| LAMP |
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see also intermediates, disorders
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)
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