Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DL-alpha-(Difluoromethyl)arginine (RMI 71 897) is an irreversible inhibitor of both the biosynthetic and biodegradative arginine decarboxylases of Escherichia coli and of the biosynthetic arginine decarboxylases of Pseudomonas aeruginosa and Klebsiella pneumoniae. The Ki is close to 800 muM for the biosynthetic decarboxylase of E. coli and 140 muM for the biodegradative enzyme while the respective half-lives (t1/2) calculated for an infinite concentration of inhibitor are 1.0 and 2.1 min. The inhibitor also blocks the arginine decarboxylase activity of E. coli and Pseudomonas aeruginosa in vivo, indicating that the compound is transported into the cell. DL-alpha-Methylarginine (RMI 71 699) was found to be a competitive inhibitor of both arginine decarboxylases from E. coli. These results suggest that it may be possible to use an arginine decarboxylase inhibitor in conjunction with known inhibitors of ornithine decarboxylase to block all putrescine biosynthesis in prokaryotic cells and thus to study the effects of such inhibition in these organisms.
 ...
PMID:DL-alpha-(Difluoromethyl)arginine: a potent enzyme-activated irreversible inhibitor of bacterial decarboxylases. 678 79

DL-alpha-Difluoromethylornithine, an enzyme-activated irreversible inhibitor of eukaryotic ornithine decarboxylase and consequently of putrescine biosynthesis, inhibited ornithine decarboxylase in enzyme extracts from Pseudomonas aeruginosa in a time-dependent manner t1/2 1 min, and also effectively blocked the enzyme activity in situ in the cell. Difluoromethylornithine, however, had no effect on the activity of ornithine decarboxylase assayed in enzyme extracts from either Escherichia coli or Klebsiella pneumoniae. However, the presence of the inhibitor in cell cultures did partially lower ornithine decarboxylase activity intracellularly in E. coli. Any decrease in the intracellular ornithine decarboxylase activity observed in E. coli and Pseudomonas was accompanied by a concomitant increase in arginine decarboxylase activity, arguing for a co-ordinated control of putrescine biosynthesis in these cells.
 ...
PMID:Difluoromethylornithine irreversibly inactivates ornithine decarboxylase of Pseudomonas aeruginosa, but does not inhibit the enzymes of Escherichia coli. 680 Mar 59

Arginine catabolism produces ammonia without transferring nitrogen to another compound, yet the only known pathway of arginine catabolism in Escherichia coli (through arginine decarboxylase) does not produce ammonia. Our aims were to find the ammonia-producing pathway of arginine catabolism in E. coli and to examine its function. We showed that the only previously described pathway of arginine catabolism, which does not produce ammonia, accounted for only 3% of the arginine consumed. A search for another arginine catabolic pathway led to discovery of the ammonia-producing arginine succinyltransferase (AST) pathway in E. coli. Nitrogen limitation induced this pathway in both E. coli and Klebsiella aerogenes, but the mechanisms of activation clearly differed in these two organisms. We identified the E. coli gene for succinylornithine aminotransferase, the third enzyme of the AST pathway, which appears to be the first of an astCADBE operon. Its disruption prevented arginine catabolism, impaired ornithine utilization, and affected the synthesis of all the enzymes of the AST pathway. Disruption of astB eliminated succinylarginine dihydrolase activity and prevented arginine utilization but did not impair ornithine catabolism. Overproduction of AST enzymes resulted in faster growth with arginine and aspartate. We conclude that the AST pathway is necessary for aerobic arginine catabolism in E. coli and that at least one enzyme of this pathway contributes to ornithine catabolism.
 ...
PMID:Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. 969 79