Activation of rat liver S-adenosylmethionine decarboxylase by putrescine and 2-substituted 1,4-butanediamines.
1. The activation of S-adenosyl-L-methionine decarboxylase (SAM-DC) by putrescine and a series of 1,4-butanediamines with a substituent in position 2 was studied. 2. Kinetic data show the activation of SAM-DC by putrescine is essentially uncompetitive. 3. All 2-substituted 1,4-butanediamines were activators, although not as potent as putrescine itself. 4. At high concentrations of SAM activation of SAM-DC by putrescine and putrescine analogs deviated considerably from uncompetitive activation kinetics. 5. In order to explain the experimental data, especially the non-linearity of the "fractional velocity plots", it was necessary to postulate two independent, but equivalent activator binding sites, for which substrate (SAM) and activator compete. 6. Based on this kinetic model an equation was derived which describes the rate of SAM decarboxylation as a function of substrate and activator concentrations. 7. From the simulated curves, approximate values for equilibrium constants for the binding of activator and substrate to the activator binding sites, and relative rate constants for the product forming steps were calculated. 8. Even a minor change of the structure, such as the substitution of one hydrogen atom by fluorine in the 2-position of putrescine had a very considerable effect on the potency of activation. 9. It is apparent that the structural requirements of an activator of SAM-DC are highly specific.
Dezeure
F
F
Merrell Dow Research Institute, Strasbourg, France.
Gerhart
F
F
Seiler
N
N
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D003959:Diamines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008297:Male; D011700:Putrescine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003959:Diamines; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D011700:Putrescine