Reactome | Conjugation of phenylacetate with glutamine

Conjugation of phenylacetate with glutamine

Stable Identifier

R-HSA-177162

Type

Pathway

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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Conjugation of phenylacetate with glutamine

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Phenylacetate metabolism is of clinical importance because its conjugation with glutamine to form phenylacetylglutamine, which can be excreted in the urine, provides an alternative pathway for nitrogen excretion in patients with urea cycle defects (James et al. 1972; Batshaw et al. 2001; Brusilow and Horwich 2001). This conjugation proceeds in two steps. First, phenylacetate and ATP react with coenzyme A to form phenylacetyl CoA, AMP, and pyrophosphate (Vessey et al. 1999). Two human CoA ligases have been characterized that catalyze this reaction efficiently in vitro: acyl-CoA synthetase medium-chain family member 1 (BUCS1) (Fujino et al. 2001) and xenobiotic/medium-chain fatty acid:CoA ligase (Vessey et al. 2003). Their relative contributions to phenylacetate metabolism in vivo are unknown. Second, phenylacetyl CoA and glutamine react to form phenyacetyl glutamine and Coenzyme A. The enzyme that catalyzes this reaction has been purified from human liver mitochondria and shown to be a distinct polypeptide species from glycine-N-acyltransferase (Webster et al. 1976). This human glutamine-N-acyltransferase activity has not been characterized by sequence analysis at the protein or DNA level, however, and thus cannot be associated with a known human protein in the annotation of phenylacetate conjugation.

Literature References

PubMed ID	Title	Journal	Year
11148549	Alternative pathway therapy for urea cycle disorders: twenty years later MacArthur, RB, Tuchman, M, Batshaw, ML	J Pediatr	2001
4403084	The conjugation of phenylacetic acid in man, sub-human primates and some non-primate species Smith, RL, Williams, RT, James, MO, Reidenberg, M	Proc R Soc Lond B Biol Sci	1972
931988	Identification of separate acyl- CoA:glycine and acyl-CoA:L-glutamine N-acyltransferase activities in mitochondrial fractions from liver of rhesus monkey and man Strong, JM, Mieyal, JJ, Lucas, SV, Webster, LT, Siddiqui, UA	J Biol Chem	1976
11470804	Molecular identification and characterization of two medium-chain acyl-CoA synthetases, MACS1 and the Sa gene product Sakai, J, Takei, YA, Kamataki, A, Takahashi, S, Fujino, T, Sone, H, Yamamoto, TT, Magoori, K, Ioka, RX	J Biol Chem	2001
	The Metabolic and Molecular Bases of Inherited Disease, 8th ed Beaudet, AL, Scriver, CR, Sly, WS, Valle, D		2001
12616642	Isolation, sequencing, and expression of a cDNA for the HXM-A form of xenobiotic/medium-chain fatty acid:CoA ligase from human liver mitochondria Kelley, M, Warren, RS, Lau, E, Vessey, DA	J Biochem Mol Toxicol	2003
10434065	Characterization of the CoA ligases of human liver mitochondria catalyzing the activation of short- and medium-chain fatty acids and xenobiotic carboxylic acids Kelley, M, Warren, RS, Vessey, DA	Biochim Biophys Acta	1999