Glutamine N-acyltransferase (GLNAT)

Glutamine N-acyltransferase (EC 2.3.1.14), also known as glutamine N-phenylacetyltransferase, is a mitochondrial Phase II drug-metabolizing enzyme primarily expressed in the human liver and kidneys (PMID: 17503907). It plays a pivotal role in the detoxification of phenylacetate by catalyzing its conjugation with L-glutamine to form phenylacetylglutamine, a compound that is rapidly excreted by the kidneys. This metabolic pathway is the primary mechanism of action for nitrogen-scavenging drugs such as sodium phenylbutyrate and glycerol phenylbutyrate, which are used to treat urea cycle disorders (UCDs) and hyperammonemia (DrugBank DB00622). Because each molecule of phenylacetylglutamine contains two nitrogen atoms, the enzyme effectively facilitates the removal of waste nitrogen, bypassing the defective urea cycle. Clinical efficacy is typically monitored by measuring urinary phenylacetylglutamine levels, which serve as a biomarker for the enzyme's metabolic throughput (PMID: 11483927). Potential therapeutic challenges include the depletion of systemic glutamine pools and the risk of phenylacetate toxicity if the enzyme's capacity is exceeded.

Other names

Glutamine N-phenylacetyltransferasePhenylacetyl-CoA:L-glutamine N-acyltransferaseGln N-acyltransferaseEC 2.3.1.14

The enzyme catalyzes the conjugation of phenylacetyl-CoA with L-glutamine to form phenylacetylglutamine, which is then excreted in the urine, thereby removing two atoms of nitrogen per molecule of glutamine and providing an alternative pathway for nitrogen excretion in patients with urea cycle disorders (DrugBank DB00622; PMID: 17503907).