Chemical Properties
White Solid
Uses
A metabolite of carboxylic acid.
Definition
ChEBI: A N-acylglycine that is glycine substituted on nitrogen with a phenylacetyl group.
Biological Activity
Phenylacetylglycine is an acylglycine. Acylglycines are normally minor metabolites of fatty acids. However, the excretion of certain acylglycines is increased in several inborn errors of metabolism. In certain cases the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation. Acylglycines are produced through the action of glycine N-acyltransferase (EC 2.3.1.13) which is an enzyme th at catalyzes the chemical reaction: acyl-CoA + glycine ↔ CoA + N-acylglycine. Phenylacetylglycine or PAG is a glycine conjugate of phenylacetic acid. Phenylacetic acid may arise from exposure to styrene (plastic) or through the consumption of fruits and vegetables. Phenylacetic acid is used in some perfumes, possessing a honey-like odour in low concentrations, and is also used in penicillin G production. PAG is a putative biomarker of phospholipidosis. Urinary PAG is elevated in animals exhibiting abnormal phospholipid accumulation in many tissues and may thus be useful as a surrogate biomarker for phospholipidosis. The presence of phenylacetylglycine in urine has been confirmed for dogs, rats and mice. However, the presence of this compound in human urine is controversial. GC-MS studies have not found this compound while NMR studies claimed to have identified it , It appears th at phenylacetylglycine may sometimes be mistaken for phenylacetylglutamine via NMR.
Synthesis
Glycine (100 mg, 1.33 mmol) was dissolved in 2 M aqueous sodium hydroxide solution (2 mL) followed by the addition of acetone (2 mL) and the reaction mixture was cooled in an ice bath. Phenylacetyl chloride (161 μL, 1.21 mmol) was slowly added dropwise while maintaining the same temperature. After the dropwise addition, the reaction system was gradually warmed up to room temperature and stirred continuously for 6 hours. Upon completion of the reaction, the solvent was removed by rotary evaporator and the residue was adjusted to pH 2-3 with 1 M hydrochloric acid solution and subsequently extracted with ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated to give phenylacetylglycine (190 mg, 81% yield) as a white solid. The product was characterized by 1H NMR (300 MHz, acetone-d6): δ= 7.41-7.20 (m, 5H), 3.95 (d, J = 5.74 Hz, 1H), 3.59 (s, 2H).13C NMR (75 MHz, DMSO-d6): δ= 171.53, 170.81, 136.32, 129.25, 128.36, 126.55, 42.15, 40.95. MALDI-TOF-MS analysis: calculated value of 194.1 and measured value of 194.1 [M + H]+ for C10H12NO3.
IC 50
β2 adrenoceptor; Microbial Metabolite; Human Endogenous Metabolite
References
[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3465 - 3469
[2] Journal fuer Praktische Chemie (Leipzig), 1888, vol. <2> 38, p. 102
[3] Journal of Biological Chemistry, 1920, vol. 43, p. 468
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 15, p. 3966 - 3970
[5] Oriental Journal of Chemistry, 2010, vol. 26, # 4, p. 1533 - 1536
