Reductive debromination of (alpha-bromoiso-valeryl)urea by intestinal bacteria.
The reductive debromination of the hypnotic (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by intestinal bacteria has been studied. The caecal contents of rats, mice, hamsters, guinea-pigs and rabbits had significant debrominating activity toward (alpha-bromoiso-valeryl)urea. The cell-free extract of intestinal bacteria from the caecal contents of rats had debrominating activity in the presence of both flavin mononucleotide (FMN) and NADH (or NADPH) under anaerobic conditions. Seven pure strains of intestinal bacteria were also tested and the highest activity was observed with Clostridium sporogenes. The cell-free extract of Clostridium sporogenes had debrominating activity in the presence of both FMN and NADH (or NADPH), and this activity was inhibited by sodium arsenite and potassium cyanide. The activity of the cell-free extract was also supported by the photochemically reduced form of FMN. The debromination in intestinal bacteria seems to proceed in two steps--reduction of flavins by bacterial flavin reductase(s) in the presence of NADPH or NADH, and then the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by bacterial dehalogenase(s) using the reduced flavins as an electron donor. These results indicate that intestinal bacteria play a role in the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea in animals. The debromination is inhibited by oxygen and dependent on flavins.
Kitamura
S
S
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
Kuwasako
M
M
Ohta
S
S
Tatsumi
K
K
D000818:Animals; D018053:Arsenites / Q000737:chemistry; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology*; D006224:Cricetinae; D038181:FMN Reductase; D005415:Flavins / Q000378:metabolism*; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology; D010100:Oxygen / Q000737:chemistry*; D011190:Potassium Cyanide / Q000737:chemistry; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017670:Sodium Compounds / Q000737:chemistry; D013045:Species Specificity; D014508:Urea / Q000031:analogs & derivatives* / Q000378:metabolism
C119881:(3-methylbutyryl)urea; C119882:(bromoiso-valeryl)urea; D018053:Arsenites; D005415:Flavins; D006993:Hypnotics and Sedatives; D011506:Proteins; D017670:Sodium Compounds; C017947:sodium arsenite; D014508:Urea; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; D011190:Potassium Cyanide; D010100:Oxygen