Disease relevance of p-Cresylic acid

• This is consistent with the dissimilar enzyme activities of FC as sulfide dehydrogenase in the phototrophic bacteria and as p-cresol methylhydroxylase in Pseudomonas [1].
• Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14, and 15 increase the uptake and toxicity of Al in cultured MH [2].
• DESIGN: Protein assimilation was evaluated in 24 healthy control subjects and in 40 patients with end-stage renal disease (ESRD; 14 treated with peritoneal dialysis and 26 with hemodialysis) by means of a [13C]protein breath test, quantification of the generation rate of p-cresol, or both methods [3].
• Regression analysis of percentage body weight gain on urinary p-cresol excretion gave a negative correlation coefficient (r = -0.73) [4].
• In vitro, aerobic bacteria tended to produce phenol from tyrosine while anaerobic bacteria produced p-cresol [5].

Psychiatry related information on p-Cresylic acid

• Time-response curves showed increased Al uptake and toxicity at p-cresol concentrations of 3 mg/dl in culture media [2].

High impact information on p-Cresylic acid

• Subunit interactions change the heme active-site geometry in p-cresol methylhydroxylase [6].
• The enzyme p-cresol methylhydroxylase [4-cresol: (acceptor) oxidoreductase (methyl-hydroxylating), EC 1.17.99.1] contains two subunits: a cytochrome c (electron transfer) subunit (cytochrome cpc) and a flavin (catalytic) subunit [6].
• Steady-state kinetic analyses carried out at pH 7.0 showed significant increases in the apparent Km for guaiacol, p-cresol, and 2, 2'-azinobis(3-ethylbenzothiazolinesulfonic acid) (ABTS) [7].
• The cytochrome subunit is necessary for covalent FAD attachment to the flavoprotein subunit of p-cresol methylhydroxylase [8].
• However, the amino acid sequence is closer to Paracoccus sp. cytochrome c554(548) (37%) than it is to the heme subunit from Pseudomonas putida p-cresol methylhydroxylase flavocytochrome c (20%) [9].

Chemical compound and disease context of p-Cresylic acid

• Compounds that have been extracted previously from these ultrafiltrate fractions (p-cresol, xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested for their effect on Al uptake and toxicity in MH at concentrations found in uremic serum [2].
• The volume of distribution of p-cresol was approximately 4 times larger than that of creatinine, but was not significantly affected by renal failure [10].
• Pseudomonas putida N.C.I.B. 9869, when grown on 3,5-xylenol, hydroxylates the methyl groups on 3,5-xylenol and on p-cresol by two different enzymes [11].
• The aromatic alcohol dehydrogenases in Pseudomonas putida N.C.I.B. 9869 grown on 3,5-xylenol and p-cresol [12].
• p-Cresol methylhydroxylase from Pseudomonas putida, an anaerobic dehydrogenase that catalyses the oxidation of p-cresol to p-hydroxybenzyl alcohol and then to p-hydroxybenzaldehyde, is an enzyme of great interest in several respects [13].

Biological context of p-Cresylic acid

• The reactions of MnPI and MnPII with p-cresol strictly obeyed second-order kinetics [14].
• The omission of T4moD causes an approximately 20-fold decrease in hydroxylation rate, nearly complete uncoupling, and a decrease in regiospecificity so that p-cresol represents approximately 60% of total products [15].
• CONCLUSION: During peritoneal dialysis p-cresol behaves like beta2m, probably due to its protein binding [16].
• Among the compounds studied, only p-cresol depressed whole blood respiratory burst reactivity (G1C-U, CL-P) dose dependently at concentrations currently encountered in end-stage renal disease (ESRD) (P < 0.05 from 5 micrograms/ml on) [17].
• Uric acid (7 mg/dL), indoxyl sulfate (5 mg/dL) and p-cresol (1.4 mg/dL), which coeluted with F1, F2 and F4, respectively, did not interfere with the inhibitory action of CTR 10-7 mol/L; however, the addition of phenol (0.14 mg/dL), which coeluted with F3, prevented the CTR-induced inhibition of parathyroid cell proliferation [18].

Anatomical context of p-Cresylic acid

• Under all treatments, p-cresol was the predominant metabolite of the volatile phenolic and aromatic metabolites detected in feces and urine, with the urine accounting for 88% of its total daily excretion [4].
• Results from studies on patients with ileostomy, colostomy, and diverticular disease indicated that p-cresol is largely produced by the anaerobic flora of the left colon while phenol was produced in the ileum (when colonized) and cecum [5].
• We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion [19].
• In this study, we investigated the in vitro effect of the uremic retention solute p-cresol on the barrier function of endothelial cells (HUVEC) [20].
• Mechanisms of uremic inhibition of phagocyte reactive species production: characterization of the role of p-cresol [17].

Associations of p-Cresylic acid with other chemical compounds

• Stopped-flow techniques were used to investigate the kinetics of the formation of manganese peroxidase compound I (MnPI) and of the reactions of MnPI and manganese peroxidase compound II (MnPII) with p-cresol and MnII [14].
• We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS [21].
• Spectrophotometric titrations indicated that the pK(a) of the phenolic proton on compound 1 (8.34) was lower than the pK(a) of tyrosine (10.1) or of p-cresol (10.2) [22].
• Phenol and p-cresol are better hydrogen bond donors than acceptors, whereas benzyl alcohol is a better acceptor than donor [23].
• Toluene 4-monooxygenase (T4MO) catalyzes the hydroxylation of toluene to yield 96% p-cresol [24].

Gene context of p-Cresylic acid

• In addition, CYP2B6 and CYP2E1 catalyzed the formation of p-cresol (11-12% of total metabolites), and CYP1A2 catalyzed the formation of both o-(22%) and p-cresol (35%) [25].
• Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase [26].
• METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta) [19].
• A sequence in the 3' non-coding region of Vibrio hollisae thermostable hemolysin gene that is highly homologous with a similar located sequence in the Pseudomonas putida p-cresol methylhydroxylase gene is also found in the 3' non-coding region of the degS homolog gene of the PPA2 [27].
• The mechanisms by which urinary p-cresol sulfate, possibly derived from tyrosine-SO(4), reflects progressive worsening that is disabling in MS are unknown [28].

Analytical, diagnostic and therapeutic context of p-Cresylic acid

• This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis [21].
• Total p-cresol excretion expressed on the metabolic body size, resulted in significant treatment differences [4].
• Phenol and p-cresol accumulated in uremic serum measured by HPLC with fluorescence detection [29].
• Both p-cresol and p-cresylglucuronide were analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC) [10].
• Superior dialytic clearance of beta(2)-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis [30].

References