Disease relevance of 7188-16-1

• Its in vivo role remains unclear, however, and the observation that expression of the Escherichia coli enzyme in vivo is regulated by both temperature and phenylacetic acid has prompted speculation that the enzyme could be involved in the assimilation of aromatic compounds as carbon sources in the organism's free-living mode [1].
• In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41) [2].
• Fourteen different genes included in a DNA fragment of 18 kb are involved in the aerobic degradation of phenylacetic acid by Pseudomonas putida U [3].
• Diclofenac sodium, a phenylacetic acid derivative, is a non-steroidal, anti-inflammatory, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and allied conditions, and in the treatment of pain resulting from minor surgery, trauma and dysmenorrhoea [4].
• Differentiation of Bacteroides fragilis species by gas chromatographic detection of phenylacetic acid [5].

Psychiatry related information on 7188-16-1

• Phenylacetic acid as an indicator in bipolar affective disorders [6].
• Urinary phenylacetic acid in panic disorder with and without depression [7].
• Changes in plasma unconjugated phenylacetic acid concentrations were significantly and negatively correlated with the corresponding changes in Hamilton Depression scores but not with eating behavior measures [8].
• A high-pressure liquid chromatographic method for plasma phenylacetic acid, a putative marker for depressive disorders [9].
• CSF phenylacetic acid and hostility in paranoid schizophrenia [10].

High impact information on 7188-16-1

• Treatment of a patient deficient in carbamyl phosphate synthetase with benzoate or phenylacetic acid resulted in an increase in urinary nitrogen, which could be accounted for by the respective amino acid acylation product, hippurate or phenylacetylgultamine [11].
• Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death [12].
• Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner [2].
• Although a recent report indicates that MHC expression influences the ratio of volatile compounds such as phenylacetic acid, so far no other means than studying the behavior of mice or rats has been available to assess odor types [13].
• This catabolic pathway appears to be organized in three contiguous operons that contain the following functional units: (i) a transport system, (ii) a phenylacetic acid activating enzyme, (iii) a ring-hydroxylation complex, (iv) a ring-opening protein, (v) a beta-oxidation-like system, and (vi) two regulatory genes [3].

Chemical compound and disease context of 7188-16-1

• Molecular characterization of the phenylacetic acid catabolic pathway in Pseudomonas putida U: the phenylacetyl-CoA catabolon [3].
• Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure [14].
• Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements [15].
• Moreover, a DNA cassette encoding the whole styrene lower pathway has been constructed and has been used to expand the ability of Pseudomonas strains to degrade phenylacetic acid [16].
• Penicillin acylase from Alcaligenes faecalis has a very high affinity for both natural (benzylpenicillin, Km = 0.0042 mM) and colorimetric (6-nitro-3-phenylacetamidobenzoic acid, Km = 0.0045 mM) substrates as well as the product of their hydrolysis, phenylacetic acid (Ki = 0.016 mM) [17].

Biological context of 7188-16-1

• METHODS: Phenylacetic acid (5 mmol/l) was used to inhibit pyruvate carboxylase in isolated rat islets, which were then assessed for insulin secretion, fuel oxidation, ATP:ADP ratio, respiration, mitochondrial membrane potential, exocytosis and ATP-sensitive K(+) channel (K(ATP)-channel) conductance [18].
• The HRP-mediated dimerization of 5 mM PHPA with concentrations of H2O2 up to 2.5 mM resulted in a linear increase in fluorescence (R = .995, n = 8) [19].
• With the ester of acetic acid, but not of propionic acid, there was a pre-steady-state exponential phase, the kinetics of which were inhibited by phenylacetic acid (a product of hydrolysis of specific substrates) to the extent predicted from Ki values [20].
• The co-existence of two functional gene clusters for the degradation of phenylacetic acid in a bacterium has not been reported so far [21].
• By following this methodology, the entire set of genes belonging to the phenylacetic acid (PhAc; 18-kb) pathway as well as those required for the synthesis and mobilization of different polyhydroxyalkanoates (PHAs; 6.4 kb) in Pseudomonas putida U were recovered directly from the bacterial chromosome and cloned into a plasmid for the first time [22].

Anatomical context of 7188-16-1

• We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) alpha agonist (compound 1) [23].
• When bovine aortic endothelial cells (BAEC) were incubated with HBSS and PHPA alone, 50% less fluorescence was observed than when HRP was added.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time [24].
• To this end, we measured the pulmonary venous effluent concentrations of the MAO substrate [(14)C]phenylethylamine and its metabolite [(14)C]phenylacetic acid after the bolus injection of either phenylethylamine or phenylacetic acid into the pulmonary artery of perfused rabbit lungs over a range of PO(2) values from 16 to 518 Torr [25].
• In vitro studies with isolated mitochondria showed that the CoA ester of phenylacetic acid was formed [26].

Associations of 7188-16-1 with other chemical compounds

• They were identified as dimethylguanosine, phenylethylamine, and phenylacetic acid by chromatography and mass spectrometry [14].
• Quantitative analysis of specific pac mRNA and a lacZ fusion to the 5'-terminal region of the pac gene demonstrated that both phenylacetic acid induction and catabolite repression by glucose are involved, at the transcriptional level, in the regulation of the pac gene [27].
• The enzyme penicillin acylase (penicillin amidohydrolase EC 3.5.1. 11) catalyses the cleavage of the amide bond in the benzylpenicillin (penicillin G) side-chain to produce phenylacetic acid and 6-aminopenicillanic acid (6-APA) [28].
• Bromfenac sodium (Duract) is a phenylacetic acid-derived nonsteroidal anti-inflammatory agent introduced in the United States in 1997 and withdrawn in 1998 [29].
• The same INC involving a complex between the benzyl radical and protonated carbon dioxide is also generated upon decarboxylation of metastable phenylacetic acid molecular ions [30].

Gene context of 7188-16-1

• Chronic kidney diseases are accompanied by the accumulation of substances like asymmetric dimethylarginine, phenylacetic acid, homocysteine, and advanced glycation end products, known to either inhibit endothelial nitric oxide synthase (eNOS) or uncouple it, consequently limiting the amount of available nitric oxide (NO) [31].
• The expression of the divergently transcribed paaZ and paaABCDEFGHIJK catabolic operons, which are responsible for phenylacetic acid (PA) degradation in Escherichia coli, is driven by the Pz and Pa promoters, respectively [32].
• Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters [33].
• Effect of heterologous expression of phaG [(R)-3-hydroxyacyl-ACP-CoA transferase] on polyhydroxyalkanoate accumulation from the aromatic hydrocarbon phenylacetic acid in Pseudomonas species [34].
• Purification and biochemical characterization of phenylacetyl-CoA ligase from Pseudomonas putida. A specific enzyme for the catabolism of phenylacetic acid [35].

Analytical, diagnostic and therapeutic context of 7188-16-1

• Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid [2].
• An HPLC procedure for the determination of total phenylacetic acid (PAA) in human plasma is described [9].
• Assay of urinary phenylacetic acid by high-performance liquid chromatography [36].
• RT-PCR analysis of the paa genes of A. evansiigrowing aerobically with PA showed a probable organization of the paa genes in three operons [37].
• In a patient with hyperargininemia, oral administration of sodium benzoate or phenylacetic acid together with an essential amino acid mixture was used to prevent hyperammonemia and to decrease plasma and CSF concentrations of arginine [38].

References