title: Effects of lipids on nucleotide inhibition of wheat-germ aspartate transcarbamoylase: evidence of an additional level of control?
abstract: Wheat-germ aspartate transcarbamoylase, a monofunctional trimer, is strongly inhibited by uridine 5'-monophosphate (UMP), which shows kinetic interactions with the substrate, carbamoyl phosphate, suggesting a classical allosteric mechanism of regulation. Inhibition of the purified enzyme by UMP was amplified in the presence of a variety of ionic lipids at concentrations low enough to preclude denaturation. In the absence of UMP, most of these compounds had no kinetic effect or were slightly activating. Two phospholipids did not show the effect. In a homologous series of fatty acids (C6-C16), the potentiating effect was only seen with homologues greater than C8, reaching a maximum at C12. The effect of dodecanoate (C12) on kinetic cooperativity (UMP as variable ligand) was studied. At each of several fixed concentrations of carbamoyl phosphate, dodecanoate had a pronounced effect on the half-saturating concentration of UMP, which was reduced by about half in every case, indicating substantially tighter binding of UMP. However, dodecanoate had relatively little effect on the kinetic Hill coefficient for the cooperativity of UMP. The possible metabolic significance of these effects is discussed.
authors.affiliation: School of Chemical and Life Sciences, University of Greenwich, Woolwich, London, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Khan
authors.forename: B Z
authors.initials: BZ
authors.lastname: Chowdhry
authors.forename: R J
authors.initials: RJ
authors.lastname: Yon
mesh_terms: D001221:Aspartate Carbamoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology*; D014908:Triticum / Q000201:enzymology*; D014542:Uridine Monophosphate / Q000494:pharmacology*
chemical_list: D003902:Detergents; D005227:Fatty Acids; D008055:Lipids; D014542:Uridine Monophosphate; D001221:Aspartate Carbamoyltransferase