Ornithine aminotransferase activity, tissue ornithine concentrations and polyamine metabolism.
1. Inactivation of L-ornithine:2-oxoacid aminotransferase (OAT) by 5-fluoromethylornithine (5FMOrn), a specific inactivator of OAT, causes a great elevation of tissue ornithine (Orn) concentrations. 2. Inhibition of L-ornithine decarboxylase (ODC) by 2-difluoromethylornithine (DFMO) had no effect on Orn concentrations. 3. The combined administration of 5FMOrn and DFMO produced a 2- to 3-fold greater enhancement of tissue Orn concentrations than treatment with 5FMOrn alone. 4. The increase of tissue Orn concentrations had a long-lasting enhancing effect on polyamine metabolism. 5. In the brain this could be demonstrated by the elevation of putrescine and spermidine concentrations and the increase of spermidine turnover rate. 6. In visceral organs polyamine concentrations were not elevated because polyamines can be eliminated by transport. 7. In line with this notion is the fact that urinary polyamine excretion was increased for several days, even after a single dose of 5FMOrn. 8. Inhibitors of 4-aminobutyric acid:2-oxoglutarate aminotransferase which are also inactivators of OAT had the same effect on polyamine excretion as 5FMOrn.
Seiler
N
N
Merrell Dow Research Institute, Strasbourg, France.
Daune
G
G
Bolkenius
F N
FN
Knödgen
B
B
D000818:Animals; D001921:Brain / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009952:Ornithine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000637:Transaminases / Q000378:metabolism*
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C057405:5-fluoromethylornithine; D009952:Ornithine; D000637:Transaminases; D009953:Ornithine-Oxo-Acid Transaminase; D000518:Eflornithine