Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:34834-67-8 (trans-3'-hydroxycotinine)
 135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sperm samples from 44 cigarette smokers and 50 nonsmokers attending an infertility clinic were examined by high-performance liquid chromatography (HPLC) assay and HPLC-mass spectrometry for the presence of nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (THOC) in seminal plasma. Smokers were found to have levels of COT and THOC in seminal plasma that were similar to those found in serum. The level of NIC was significantly increased in seminal plasma compared to serum. Total motility of spermatozoa was significantly and negatively correlated to COT and THOC levels in seminal plasma. Forward motility of spermatozoa was correlated only with cotinine semen levels. On the basis of these results, we suggest that the presence of tobacco smoke constituents in seminal plasma could provide a warning of the adverse effects of cigarette smoke on the physiology of reproduction.
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PMID:Nicotine, cotinine, and trans-3-hydroxycotinine levels in seminal plasma of smokers: effects on sperm parameters. 824 41

A simple and reliable reversed-phase high-performance liquid chromatographic method with ultraviolet detection is described for the quantitation of nicotine and its metabolites cotinine, trans-3'-hydroxycotinine, norcotinine and cotinine N-oxide in human serum. The analytes and the internal standard, N-ethylnorcotinine, were extracted by solid-phase extraction before chromatography. Two different columns and mobile phases with gradient systems were used. The detection limit of the assay was 10 ng/ml for nicotine, 3 ng/ml for cotinine N-oxide and 5 ng/ml for cotinine, trans-3'-hydroxycotinine and norcotinine. The concentrations of nicotine and its metabolites in the serum of 12 cigarette smokers are reported.
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PMID:Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection. 829 47

The 1,3-diethyl-2-thiobarbituric acid (DETBA) assay for nicotine metabolites has been improved so that it can be used to determine the concentrations of nicotine and up to 12 metabolites in the urine of humans and laboratory animals, including phase 2 metabolites. The products of beta-glucuronidase cleavage found in human urine were mainly trans-3'-hydroxycotinine, cotinine, and a small amount of nicotine. Following isolation, spectroscopic analyses showed the structure of the nicotine DETBA derivative to be the one-to-one ring-opening product of DEBTA and the cyanopyridinium salt of nicotine.
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PMID:High-performance liquid chromatographic determination of nicotine and its urinary metabolites via their 1,3-diethyl-2-thiobarbituric acid derivatives. 845 8

A rapid and selective assay of nicotine, cotinine and trans-3'-hydroxycotinine in human serum, based on high-performance liquid chromatography with UV detection has been developed. The compounds were subjected to solid-phase extraction, using Extrelut 1 cartridges. Recoveries were ca. 95% for nicotine, 90% for cotinine and 50-55% for trans-3'-hydroxycotinine. The limit of quantitation observed with this method was 10 ng/ml for nicotine and 5 ng/ml for each of the metabolites. The compounds were also identified using high-performance liquid chromatography with particle beam mass spectrometry, to confirm their presence in human serum.
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PMID:Determination of nicotine and two major metabolites in serum by solid-phase extraction and high-performance liquid chromatography, and high-performance liquid chromatography-particle beam mass spectrometry. 846 78

Nicotine and its main metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine glucuronide, nicotine-1'-N-oxide and 3-pyridylcarbinol) were analysed in urine after liquid-liquid extraction by high-performance liquid chromatography using norephedrine as internal standard, ultraviolet detection at 260 nm and scanning ultraviolet spectra with a photodiode-array detector. The conjugated trans-3'-hydroxycotinine was determined after enzymatic hydrolysis. Specific determination of 3-pyridylcarbinol was also carried out. Owing to its good selectivity, sensitivity and reproducibility, the method was applied to the analysis of urine samples from smokers and non-smokers. The results obtained suggest that the urinary markers used to assess active smoking or exposure to environmental tobacco smoke must be not only nicotine and cotinine, but also their main free and conjugated metabolites.
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PMID:Determination of nicotine and its main metabolites in urine by high-performance liquid chromatography. 846 89

Nicotine is primarily metabolized to cotinine, and cotinine is further metabolized to trans-3'-hydroxycotinine in human liver, which is a major metabolite of nicotine in humans. We studied the formation of trans-3'-hydroxycotinine from cotinine in human liver microsomes. trans-3'-Hydroxycotinine formation demonstrated single enzyme Michaelis-Menten kinetics (Km, 234.5 +/- 26.8 MicroM; Vmax, 37.2 +/- 2.4 pmol/min/mg protein). Significant correlation (r = .967, P < .001) between cotinine 3'-hydroxylase activities at low (50 microM) and high (1 microM) cotinine concentrations in 20 human liver microsomes suggested the contribution of a single enzyme to cotinine 3'-hydroxylation. The cotinine 3'-hydroxylase activity correlated significantly with immunoreactive cytochrome P450 (CYP)2A6 contents (r = .756, P < .01) and coumarin 7-hydroxylase activity (r = .887, P < .001). The cotinine 3'-hydroxylase activity was inhibited by coumarin, alpha-naphthoflavone, chlorzoxazone and anti-rat CYP2A1 antibodies. Microsomes of B-lymphoblastoid cells expressing human CYP2A6 exhibited cotinine 3'-hydroxylase activity. The Km value of the expressed CYP2A6 (264.7 microM) was almost identical to that of human liver microsomes. In conclusion, cotinine 3'-hydroxylation appears to be catalyzed solely by CYP2A6 in humans. Cotinine is a candidate for a new substrate for CYP2A6 in humans.
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PMID:Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes. 862 11

trans-3'-Hydroxycotinine (THOC) has been recognized as the most abundant metabolite of nicotine. In an attempt to assess THOC and cotinine (COT) concentrations during nicotine transdermal therapy, we developed a new quantitative gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of total and free THOC and COT in human urine. The method utilizes the following: (a) hydrolysis of conjugated THOC and COT by beta-glucuronidase; (b) basic extraction of THOC and COT with mixed dichloromethane and n-butyl acetate; (c) derivatization of THOC with bis(trimethylflurosilyl)acetamide; and (d) separation and identification by GC-MS with selective ion monitoring. Lower limits of quantification for the assay were 50 and 20 microg/L for THOC and COT, respectively. The intra- and interassay CVs were 4.4% and 11% for THOC, and 3.9% and 10% for COT at 1000 microg/L. The results from six consecutive 24-h urine collections in 71 subjects administered daily transdermal nicotine doses of 11, 22, and 44 mg showed that, on average, free THOC was 76% of total THOC and free COT was 48% of total COT in all subjects. THOC is the major metabolite of nicotine and constitutes 20% of total nicotine intake at steady state, whereas urinary nicotine and COT excretion were 8% and 17%, respectively. The method is useful for simultaneous determination of free and total THOCand COT and can be used to assess the urinary excretion of these metabolites during transdermal nicotine therapy.
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PMID:A new gas chromatography-mass spectrometry method for simultaneous determination of total and free trans-3'-hydroxycotinine and cotinine in the urine of subjects receiving transdermal nicotine. 989 42

1. The adverse effect of passive smoke exposure on the respiratory tract, particularly in infants and children, is not an issue of dispute. It was the objective of this study to analyse the extent and the intensity of passive smoke exposure in infants and children with respiratory tract diseases, and compare the information obtained with parents' subjective assessment. At the time of admission to the hospital, the parents of 295 infants and children (aged 1 month to 11 years) were questioned by the physician as to the smoking habits in the families' homes. An HPLC method was employed to determine simultaneously nicotine, cotinine and trans-3'-hydroxycotinine in the children's urine. 2. The sum of the nicotine metabolites turned out to be a sensitive marker in determining passive smoke exposure. Measurements revealed passive smoke exposure in 66% of the children, the frequency in younger children being significantly (P < 0.001) higher than in children over 5 years (84% vs 52%). The average concentration of nicotine metabolites in younger passive smokers was significantly (P < 0.001) higher when compared to the older ones (193 nmol/l vs 86 nmol/l). Forty-nine per cent of the parents assessed that their children had experienced passive smoke exposure, and another 10% emphasised that they only smoked in the absence of their child. In children with cystic fibrosis and bronchial asthma, the number of passive smokers as assessed by their parents were lower by 65% and 29% respectively when compared to the findings obtained from measurements. In children without respiratory diseases, the difference was as little as 18%. 3. Parents when questioned in conjunction with an illness of their children, tended to understate, or even withhold the truth about, passive smoke exposure. Therefore, reliable information on passive smoke exposure of patients can only be obtained through objective measurements.
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PMID:Passive smoke exposure in infants and children with respiratory tract diseases. 1033 4

The primary metabolite of nicotine in smokers is cotinine. Cotinine is further metabolized to trans-3'-hydroxycotinine, the major urinary metabolite of nicotine in tobacco users. It was recently reported that cytochrome P450 2A6 catalyzes the conversion of cotinine to trans-3'-hydroxycotinine. In this work, we report that P450 2A6 metabolizes cotinine not only to trans-3'-hydroxycotinine but also to 5'-hydroxycotinine, norcotinine, and a fourth as yet unidentified metabolite. The products of baculovirus-expressed P450 2A6 [methyl-(3)H]cotinine metabolism were analyzed by radioflow HPLC. Three (3)H-labeled metabolites were detected and were present in approximately equal amounts. The identities of two of the metabolites were confirmed to be 5'-hydroxycotinine and trans-3'-hydroxycotinine by LC/MS/MS and LC/MS analysis and comparison to standards. The third product was not identified. A fourth product of P450 2A6-catalyzed cotinine metabolism was detected by LC/MS. It was identified by cochromatography with a standard and MS and MS/MS data to be norcotinine. An attempt was made to further characterize the unidentified (3)H-labeled metabolite by comparison to the cotinine metabolites generated by hamster liver microsomes. Hamster liver microsomes contain a P450, 2A8, which is closely related to P450 2A6, and have previously been shown to metabolize cotinine to three hydroxylated products, trans-3'-hydroxycotinine, 5'-hydroxycotinine, and N-(hydroxymethyl)norcotinine. We were unable to confirm that N-(hydroxymethyl)norcotinine was the unidentified cotinine metabolite generated by P450 2A6.
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PMID:Characterization of multiple products of cytochrome P450 2A6-catalyzed cotinine metabolism. 1040 4

The effects of watercress consumption on the metabolism of nicotine in smokers were examined. Watercress is a rich source of phenethyl isothiocyanate (PEITC), an effective chemopreventive agent for cancers of the lung and esophagus induced in rodents by nitrosamines, including the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. PEITC is believed to inhibit nitrosamine carcinogenesis in rodents by inhibiting specific cytochrome P450 (P450) enzymes. Among the P450s involved in the activation of these nitrosamines are members of the 2A family. P450 2A6 is believed to be involved in the metabolism of both nicotine and its major metabolite cotinine. Therefore, we hypothesized that watercress consumption might inhibit nicotine and cotinine metabolism in smokers. The urine samples analyzed in this study were the same ones that we used in an earlier study (S. S. Hecht et al., Cancer Epidemiol. Biomark. Prev., 4: 877-884, 1995), in which we showed that watercress consumption increased levels of two metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNAL and its glucuronide NNAL-Gluc. This increase was attributed either to inhibition of cytochromes P450 or induction of glucuronidation. In the present study, we quantified urinary nicotine and seven of its metabolites. There were no effects of watercress consumption on levels of nicotine, cotinine, trans-3'-hydroxycotinine, 4-oxo-4-(3-pyridyl)butanoic acid, or 4-hydroxy-4-(3-pyridyl)butanoic acid, indicating either that watercress ingestion has little effect on the oxidative metabolism of nicotine (presumably by P450 2A6 or other P450 enzymes) or that these enzymes are not important for nicotine and cotinine metabolism in smokers. However, watercress consumption resulted in a significant increase compared to baseline levels of the glucuronides of cotinine (25%, P = 0.031) and trans-3'-hydroxycotinine (33%, P = 0.043) during the period when it was consumed and in a nonsignificant increase in levels of the glucuronide of nicotine. These levels returned to baseline values after the watercress consumption period. There was a correlation between increases in levels of the glucuronides of trans-3'-hydroxycotinine and NNAL in the same subjects, suggesting the involvement of a common enzyme. Thus, the results of this study suggest that PEITC or another component of watercress induces UDP-glucuronosyltransferase activity in humans.
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PMID:Effects of watercress consumption on urinary metabolites of nicotine in smokers. 1054 20


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