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Biomedical subjects

M Tateishi

Publications and source records attributed to M Tateishi.

At least 91 records · Page 5Linked to original sources

Purification and characterization of C-S lyase from Fusobacterium varium. A C-S cleavage enzyme of cysteine conjugates and some S-containing amino acids.

An enzyme responsible for the carbon-sulfur bond cleavage of various S-aryl, S-aralkyl, and S-alkyl cysteines has been purified about 270-fold from Fusobacterium varium. Incubation of a cysteine conjugate of p-bromobenzene with the enzyme yielded equimolar amounts of p-bromobenzenethiol, pyruvic acid, and ammonia, indicating that the carbon-sulfur bond cleavage proceeds via an alpha, beta-elimination reaction. The enzyme activity was inhibited either by hydroxylamine or KCN and stabilized by pyridoxal phosphate, which probably acted as cofactor. The broad substrate spectrum of this enzyme suggested an important role of the intestinal microflora in the in vivo formation of methylthio-containing metabolites of various xenobiotics.

Chromatography, DEAE-Cellulose↗

Metabolism of tenoxicam in rats.

The structures of six metabolites of tenoxicam in rats (2 mg/kg, orally), elucidated by physicochemical analyses or the reverse-isotope dilution method, were 5'-hydroxytenoxicam (5% dose), 3-(methylsulphamoyl)-2-thiophenecarboxylic acid (9% dose), and the C-7 or C-8 O-glucuronide of tenoxicam (30% dose). The mechanism of formation of N-methylthiophenesulphimide, a possible precursor of 3-(methylsulphamoyl)-2-thiophenecarboxylic acid from tenoxicam, is discussed.

Animals↗

Sensitivity to functors in Japanese aphasics.

Forty-two aphasic patients (11 amnesic, 11 Wernicke's, and 20 Broca's) and 10 controls were tested for sensitivity to functors in affirmative declarative sentences with sentence- verification tasks. The stimuli were constructed according to the following factors: Reversibility of Subject and Object, Voice, Word Order and Truth. The task required the subject to decide if a sentence presented auditorily was true or false with respect to a picture. The results indicated that functors differed among themselves in their understandability depending on sentence types in which they were embedded, and that there were no qualitative differences in sensitivity to functors among different clinical types of aphasia.

Adult↗

TnA-directed deletion of the trp operon from RSF2124-trp in Escherichia coli.

Plasmid pMT-trp was constructed by digestion of RSF2124-trp with restriction endonuclease PstI and ligation with T4 ligase. In pMT-trp about 78% of the DNA of transposon TnA from RSF2124-trp was deleted, and hence the gene for ampicillin resistance was lost. All Trp- segregants from pMT-trp carriers in Escherichia coli W3110 and its derivatives were found to have lost the entire plasmid. On the other hand, deletion plasmids which had lost the trp operon were found among Trp- segregants from RSF2124-trp carriers, particularly from the mutant strain trpAE1 trpR tnaA. The experimental fact that deletion occurred exclusively in RSF2124-trp suggests that the presence of TnA in the plasmid (RSF2124-trp) was responsible for the deletion.

Ampicillin↗

Cysteine conjugate beta-lyase in rat liver. A novel enzyme catalyzing formation of thiol-containing metabolites of drugs.

A novel enzyme catalyzing cleavage of the thioether linkage in cysteine conjugates of aromatic compounds, such as 2,4-dinitrobenzene and p-bromobenzene, has been purified about 500-fold from rat liver cytosol. Incubation of S-(2,4-dinitrophenyl)cysteine with the enzyme preparation yielded 2,4-dinitrobenzenethiol, pyruvic acid, and NH3 at equimolar ratios, indicating that the thioether cleavage probably proceeds via an alpha,beta elimination reaction. The thiol product was methylated and the methylated derivative 1-methylthio-2,4-dinitrobenzene, was identified by mass spectrometry and proton NMR spectroscopy. The Km value of S-(2,4-dinitrophenyl)cysteine was 0.5 mM at pH 7.4 in phosphate buffer. The enzyme activity was inhibited by hydroxylamine. No cofactor requirement was observed. A combination of the partially purified enzyme and hepatic microsomes that contain thiol methyltransferase (EC 2.1.1.9) converted cysteine conjugates of 2,4-dinitrobenzene and p-bromobenzene to the corresponding methylthio-containing metabolites; S-adenosylmethionine was required. An important role of this novel beta-lyase enzyme in the formation of methylthio-containing metabolites of various drugs is indicated.

Animals↗

The metabolism of isopropylantipyrine in the rat and man.

1. The major urinary metabolite of isopropylantipyrine in the rat and man was an enol glucuronide of N-desmethyl isopropylanipyrine, which comprised about 80% of the whole urinary metabolites. 2. Six other minor metabolites occurred in rat urine; all lacked the N-methyl group of the parent drug, and some had undergone further oxidation at the isopropyl group, the phenyl group or in the C-4 position.

Animals↗

A new metabolic pathway of bromazepam involving attachment of a methylthio group.

1. The structures of three hitherto unidentified metabolites of bromazepam in the rat were elucidated using u.v., mass, n.m.r. and i.r. spectrometry. 2. All three metabolites contained a methylthio or corresponding oxidized group at the C-6' position of the pyridyl moiety. 3. Quantitative analysis of the metabolites determined after administration of [14C]bromazepam to rat revealed that the three metabolites together comprised about 6% of the total radioactivity excreted in the 24-h urine, or about 1% of the dose.

Animals↗