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Pathway Description
Phenylacetate Metabolism
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2022-10-17
Phenylacetate (or phenylacetic acid) metabolism involves two steps. The first step is the conversion of phenylacetate into phenylacetyl-CoA which is catalyzed by acyl-coenzyme A synthetase ACSM1 or acyl-coenzyme A synthetase ACSM2B. Coenzyme A and ATP are also involved in this first step and AMP and pyrophosphate will be generated during the first step of metabolism. In the second step, phenylacetyl-CoA and L-glutamine interacts with glycine N-acyltransferase to generate coenzyme A as well as phenylacetylglutamine, of which the latter will be excreted in the urine. Phenylacetate metabolism provides a route that facilitates the excretion of nitrogen for patients with urea cycle defects; hence, it is important for clinical purposes.
References
Phenylacetate Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Fujino T, Takei YA, Sone H, Ioka RX, Kamataki A, Magoori K, Takahashi S, Sakai J, Yamamoto TT: Molecular identification and characterization of two medium-chain acyl-CoA synthetases, MACS1 and the Sa gene product. J Biol Chem. 2001 Sep 21;276(38):35961-6. doi: 10.1074/jbc.M106651200. Epub 2001 Jul 24.
Pubmed: 11470804
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Pubmed: 15489334
Vessey DA, Kelley M, Warren RS: Characterization of the CoA ligases of human liver mitochondria catalyzing the activation of short- and medium-chain fatty acids and xenobiotic carboxylic acids. Biochim Biophys Acta. 1999 Aug 5;1428(2-3):455-62. doi: 10.1016/s0304-4165(99)00088-4.
Pubmed: 10434065
van der Westhuizen FH, Pretorius PJ, Erasmus E: The utilization of alanine, glutamic acid, and serine as amino acid substrates for glycine N-acyltransferase. J Biochem Mol Toxicol. 2000;14(2):102-9.
Pubmed: 10630424
Matsuo M, Terai K, Kameda N, Matsumoto A, Kurokawa Y, Funase Y, Nishikawa K, Sugaya N, Hiruta N, Kishimoto T: Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2012 Apr 20;420(4):901-6. doi: 10.1016/j.bbrc.2012.03.099. Epub 2012 Mar 27.
Pubmed: 22475485
Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. doi: 10.1038/nature04632.
Pubmed: 16554811
Vessey DA, Lau E, Kelley M, Warren RS: Isolation, sequencing, and expression of a cDNA for the HXM-A form of xenobiotic/medium-chain fatty acid:CoA ligase from human liver mitochondria. J Biochem Mol Toxicol. 2003;17(1):1-6. doi: 10.1002/jbt.10056.
Pubmed: 12616642
Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004 Aug 5;23(35):5901-11. doi: 10.1038/sj.onc.1207782.
Pubmed: 15221005
Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. doi: 10.1038/nature03187.
Pubmed: 15616553
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