High impact information on CCRIS 5816

• Femoral artery flow was monitored continuously using a Doppler flow probe, and muscle microvascular recruitment was assessed by metabolism of infused 1-methylxanthine (1-MX) and by contrast-enhanced ultrasound (CEU) [1].
• Whole-body glucose infusion rate (GIR), hindleg glucose uptake, femoral blood flow (FBF), vascular resistance, and capillary recruitment, as measured by metabolism of infused 1-methylxanthine (1-MX), were assessed [2].
• The reductive half-reaction of xanthine oxidase with substoichiometric concentrations of xanthine and 1-methylxanthine at pH 10 and 8.5 has been examined by UV-visible stopped-flow and rapid-quench electron paramagnetic resonance (EPR) kinetic experiments [3].
• Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (AAMU) and 1-methylxanthine (1-MX), after ingestion of a single 200 mg dose of caffeine [4].
• 5. The final preparation exhibited 3- and 1-N-methyltransferase activity with a broad substrate specificity, showing high activity toward paraxanthine, 7-methylxanthine, and theobromine and low activity with 3-methylxanthine and 1-methylxanthine [5].

Biological context of CCRIS 5816

• The genotypes were compared to their in vivo acetylator phenotypes which were determined by measuring 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine following administration of caffeine [6].
• In this paper we describe the kinetics of formation of 1-methylxanthine (1-MX), 3-methylxanthine (3-MX) and 1,3-dimethyluric acid (1,3-DMU) from theophylline in human liver microsomal incubations and use the selective inhibitor approach to define the role of the individual cytochrome P450s (CYP) in each pathway [7].
• Caffeine has been proposed as a marker for drug acetylation on the basis of a ratio of urinary metabolites (5-acetylamino-6-formylamino-3-methyl uracil and 1-methylxanthine, AFMU:MX) determined by high-performance liquid chromatography [8].
• In the present study the effect of methylxanthines including caffeine, theophylline, theobromine (theobromine sodium salicylate), paraxanthine, and 1-methylxanthine was compared in order to analyze the structure-activity relationship [9].

Anatomical context of CCRIS 5816

• The metabolism of infused 1-methylxanthine (1-MX) to 1-methylurate (1-MU) by capillary endothelial xanthine oxidase of the constant-flow perfused rat hindlimb was shown previously to decrease with oxygen uptake (VO2) when nutritive flow was decreased [10].

Associations of CCRIS 5816 with other chemical compounds

• The population exhibited a trimodal distribution of acetylator phenotype determined by use of the 5-acetylamino-6-amino-3-methyluracil/1-methylxanthine ratio (normality test; p = 0.004) [11].
• Theophylline, its demethylated metabolites (3-methylxanthine and 1-methylxanthine), and its hydroxylated metabolite (1,3-dimethyluric acid) were measured by high-pressure liquid chromatography, and Km and Vmax values were estimated [12].
• In vivo acetylator phenotypes were categorized by determining the amounts of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine in urine after the administration of a 200 mg dose of caffeine [13].
• 2. Whole-body glucose infusion (GIR), femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, and muscle cGMP were determined [14].
• This conclusion is supported by the observations that the stoichiometry between oxygen utilization and methylurate formation was not consistent with catalysis by the oxidase form of the enzyme and that NADH formed from the metabolism of ethanol strongly inhibited 1-methylxanthine oxidation [15].

Gene context of CCRIS 5816

• We report a liquid chromatographic method for the simultaneous quantitative analysis of the five urinary metabolites of caffeine used for the CYP1A2, XO and NAT2 phenotyping studies: AAMU, AFMU, 1-methylxanthine, 1-methyluric acid and 1,7-dimethyluric acid [16].
• The formation of 1-methylxanthine was 97.6 and 100 percent of the control, and 1.3-dimethyluric acid formation was 88.9 and 95.2 percent of control at 100 microM and 500 microM RPR 102341, respectively [17].
• The glycogen fall is unaffected by prolonged calcium depletion or by 3-isobutyl 1-methylxanthine, an adenosine antagonist [18].
• 4. The conversion of 1-methylxanthine (1-MX), another secondary metabolite of CA, to 1-methyluric acid (1-MU) is catalyzed by xanthine oxidase (XO), and the urinary 1-MU to 1MX ratio reflects XO activity [19].

Analytical, diagnostic and therapeutic context of CCRIS 5816

• The ELISA phenotypes by measuring the ratio of 5-acetamido-6-amino-3-methyluracil (AAMU) and 1-methylxanthine (1X) after transformation of 5-acetamido-6-formylamino-3-methyluracil (AFMU) to AAMU, in contrast to capillary electrophoresis high-pressure liquid chromatography (HPLC) which phenotype by measuring the AFMU/1X ratio [20].
• The metabolic ratio (MR) of 5-acetylamino-6-formylamino-1-methyluracil (AFMU) to 1-methylxanthine (MX) was determined by HPLC [21].
• The effect of serotonin (5-HT) on the metabolism of infused 1-methylxanthine (1-MX), a putative substrate of capillary endothelial xanthine oxidase (XO), and on the distribution of infused fluorescent microspheres (15 microns) by the artificially constant-flow perfused rat hindlimb preparation was investigated [22].

References