EFFECTS OF LIPIDS ON NUCLEOTIDE INHIBITION OF WHEAT-GERM ASPARTATE TRANSCARBAMOYLASE - EVIDENCE OF AN ADDITIONAL LEVEL OF CONTROL

Wheat-germ aspartate transcarbamoylase, a monofunctional trimer, is st rongly inhibited by uridine 5'-monophosphate (UMP), which shows kineti c interactions with the substrate, carbamoyl phosphate, suggesting a c lassical allosteric mechanism of regulation. Inhibition of the purifie d enzyme by UMP was amplified in the presence of a variety of ionic li pids at concentrations low enough to preclude denaturation. In the abs ence of UMP, most of these compounds had no kinetic effect or were sli ghtly activating. Two phospholipids did not show the effect. In a homo logous series of fatty acids (C-6-C-16), the potentiating effect was o nly seen with homologues greater than C-8, reaching a maximum at C-12. The effect of dodecanoate (C-12) on kinetic cooperativity (UMP as var iable ligand) was studied. At each of several fixed concentrations of carbamoyl phosphate, dodecanoate had a pronounced effect on the half-s aturating concentration of UMP, which was reduced by about half in eve ry case, indicating substantially tighter binding of UMP. However, dod ecanoate had relatively little effect on the kinetic Hill coefficient for the cooperativity of UMP. The possible metabolic significance of t hese effects is discussed.