Inhibition of liver prenyltransferase by citronellyl and geranyl phosphonate and phosphonylphosphate.
Citronellyl- and geranylphosphonic acids and the corresponding phosphonylphosphates were made and tested as inhibitors of liver prenyltransferase. Kinetic analysis showed that citronellyl- and geranylphosphonylphosphate were powerful inhibitors of the enzyme, and that they were competitive inhibitors with geranyl diphosphate and noncompetitive inhibitors with isopentenyl diphosphate. Two inhibition constants, representing the equilibria [E][I]/[EI] = K5 and [ES1][I]/[ES1I] = K9, have been defined for the inhibitors. For citronellylphosphonylphosphate, the value of K5 was 1.25 microM and K9 was 3.30 microM; for geranylphosphonylphosphate, K5 = 1.50 microM and K9 = 1.60 microM. The phosphonates were very poor linear mixed noncompetitive inhibitors with respect to both substrates of the transferase.
D000080462:Acyclic Monoterpenes; D000818:Animals; D004122:Dimethylallyltranstransferase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D013058:Mass Spectrometry; D039821:Monoterpenes; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D013729:Terpenes / Q000494:pharmacology*; D014166:Transferases / Q000037:antagonists & inhibitors*
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D009943:Organophosphorus Compounds; D013729:Terpenes; D014166:Transferases; D004122:Dimethylallyltranstransferase; C007836:geraniol; C007078:citronellol