Tsutomu Yamaha

The biosynthesis of plant glycosides. I. Monoglucosides

Abstract An enzyme from wheat germ which catalyzes the formation of glucosides from phenols and uridinediphosphate glucose has been partially purified. With hydroquinone as substrate, arbutin was found to be formed as follows: UDPG + hydroquinone → UDP + arbutin Arbutin was identified by paper chromatography in several solvents either directly or after hydrolysis with acid or β-glucosidase. The rate of reaction with different phenols decreased in the order: hydroquinone > hydroxyhydroquinone > methoxyhydroquinone > resorcinol > pyrogallol > pyrocatechol.

The biosynthesis of plant glycosides. II. Gentiobiosides

Abstract An enzyme from wheat germ which catalyzes the reaction: UDPG + phenol β-glucoside → UDP + phenol β-gentiobioside has been purified and separated from the enzyme which leads to the formation of glucosides. The enzyme was found to be specific for phenol β-glucosides and substituted phenol β-glucosides (such as arbutin, salicin, p - and m -methoxyphenol glucoside, resorcinol glucoside, and mandelonitrile glucoside). Free sugars, disaccharides, or polysaccharides were not used as substrates.

Metabolism and disposition of the flame retardant plasticizer, tri-p-cresyl phosphate, in the rat.

The metabolism and disposition of tri-p-cresyl phosphate (TPCP) were studied in the rat after a single oral administration of [methyl-14C] TPCP. At a dosage of 7.8 mg/kg, most of the administered radioactivity was excreted in the urine (41%) and feces (44%) in 7 days. For 3 days, the expiratory excretion as 14CO2 amounted to 18% of the radioactivity, but was reduced to 3% by treatment of the animal with neomycin. In separate rats, the biliary excretion amounted to 28% of the dose in 24 hr. At a dose of 89.6 mg/kg, the radioactivity was excreted in urine (12%) and feces (77%) in 7 days, and the expired air (6%) in 3 days. At 24, 72, and 168 hr after oral administration, the concentration of radioactivity was relatively high in adipose tissue, liver, and kidney. The major urinary metabolites were p-hydroxybenzoic acid, di-p-cresyl phosphate (DCP), and p-cresyl p-carboxyphenyl phosphate (1coDCP). The biliary metabolites were DCP, 1coDCP, and the oxidized triesters, di-p-cresyl p-carboxyphenyl phosphate (1coTPCP), and p-cresyl di-p-carboxyphenyl phosphate (2coTPCP). The main fecal metabolite was TPCP, and the others were similar to those of bile. Following oral administration, TPCP was absorbed from the intestine, distributed to the fatty tissues, and moderately metabolized to a variety of products of oxidation and dearylation of TPCP, which were then excreted in the urine, feces, bile, and expired air. The intestinal microflora appeared to play an important role in degrading biliary metabolites to 14CO2 through the enterohepatic circulation in rats.

Excretion, distribution and metabolism of 1,2,4-trichlorobenzene in rats

Abstract1,2,4-Trichlorobenzene (TCB) labeled with C-14 was given perorally to rats at a dosage of 50 mg/kg for excretion and distribution studies.About 66% and 17% of the oral dose was excreted in the urine and feces, respectively, within 7 days. Trapped radioactivity in the expired air amounted to 2.1% of the dose, but production of labeled carbon dioxide was negligible. Tissue residues were evenly distributed throughout the organs and tissues examined, except for the adipose tissue which consistently had a little higher concentration.The urinary, fecal and expiratory metabolites were identified. Free 2,4,5- and 2,3,5-trichlorophenol (TCP) and their conjugates were mainly detected in the urine. 5- or 6-Sulfhydryl, methylthio, methylsulfoxide and methylsulfone derivatives of TCB were also detected as minor metabolites. Dichlorobenzenes and unchanged TCB were confirmed in the expired air. Reductive dechlroination seems to be catalysed by intestinal microflora enzymes.

Oxygen-18 studies on the oxidative deamination mechanism of alicyclic primary amines in rabbit liver microsomes

Abstract The mechanism of microsomal oxidative deamination of alicyclic primary amines: cyclopentylamine, cyclohexylamine, cycloheptylamine, 1- and 2-aminoindan, 1- and 2-aminotetralin, was studied under an atmosphere of 18O2 or in a medium containing H218O. The oxygen-18 contents of the products determined by gas-liquid chromatography/mass spectrometry revealed that almost all (75–100 atom%) of the oxygen of oximes was derived from molecular oxygen, whereas a part (4–25 atom% ) of the oxygen of ketones. The studies on the hydrolysis of oximes and the oxygen exchange reaction of ketones proved that the latter proceeded at a considerable rate ( t 1 2 = 9.5–336 min ) and the former made a minor contribution, to explain why the major portion (75–96 atom%) of the oxygen in ketones was derived from water. The results support the mechanism that microsomal deamination proceeds mainly through a carbinolamine intermediate, which is initially hydroxylated at the α carbon to the amino group, partially equilibrating with the imine, and then rearranges to form a ketone and ammonia.

Oxidative Deamination of Alicyclic Primary Amines by Liver Microsomes from Rats and Rabbits

1. Substrate selectivity and species difference in the oxidative deamination of the alicyclic primary amines, cyclopentylamine, cyclohexylamine, cycloheptylamine, 1- and 2-aminoindane, and 1- and 2-aminotetralin were studied using liver microsomes from rats and rabbits. 2. The deamination rates of the amines were much greater with liver microsomes from rabbits than from rats. Substrate selectivity resulted in much faster deamination of 1-aminoindane and 1-aminotetralin than of the corresponding 2-amino compounds, especially in rats. 3. When 1-aminoindane and 1-aminotetralin were incubated with rat liver microsomes and NADPH under 18O2, oxygen-18 was incorporated into the deaminated products, 1-indanone and 1-tetralone. The carbinolamine is a key intermediate in the oxidative deamination by rat liver microsomes, indicating the contribution of cytochrome P-450-dependent alpha-C-oxidation to the reaction. 4. Alicyclic primary amines gave type II binding spectra with rat and rabbit liver microsomes, but the spectra appeared to contain type I components. 5. The ratios of the alcohols, cyclohexanol, 2-tetralol and 2-indanol in the deaminated products were high in both rats and rabbits. The ketones were precursors of the alcohols, and substrate selectivity in reduction of the alicyclic ketones with NADPH was similar in both species.

加硫促進剤, N-Cyclohexyl-2-benzothiazyl Sulfenamide (CBS) のラットによる吸収, 分布, 代謝および排泄

Absorption, distribution, metabolism and excretion were studied in rats following a single oral administration of N-cyclohexyl-2-benzothiazyl sulfenamide (CBS) at a dose of 250 mg/kg. About 65% and 24% of the dose were excreted into urine and feces, respectively, for 3 days after administration of labeled CBS (cyclohexyl-14C). Biliary excretion amounted to about 5% of the dose for 3 days. While about 92% of the dose was recovered in urine and feces at a ratio of 1:1 within 3 days when 14C-2CBS was given. No specific organ-affinity was observed in distribution study. Cyclohexylamine and 2-mercaptobenzothiazole were identified as urinary metabolites.