Synthesis of menaquinone-2 derivatives as substrates for the liver microsomal vitamin K-dependent carboxylase.
The rat liver microsomal vitamin K-dependent carboxylase catalyzes the carboxylation of glutamyl to gamma-carboxyglutamyl residues in the presence of reduced vitamin K, O2 and CO2. The specificity of the enzyme for the vitamin substrate has been probed by the synthesis of a number of menaquinone-2 (2-methyl-3-geranyl-1,4-naphthoquinone) derivatives. The 2-des-methyl and 2-ethyl-MK-2 derivatives had very low activity as substrates. The 6- or 7-methyl-MK-2 derivatives and (6,7)-chloro-MK-2 were relatively high Vmax substrates with Km values increased over that seen for K-2. The 5- or 8-methyl-MK-2 derivatives were low Vmax substrates but also demonstrated low Km values. Although these observations suggested that 5-methyl-MK-2 might be a competitive inhibitor of the carboxylation reaction, it was not an effective inhibitor of either phylloquinone or 6-methyl-MK-2-dependent carboxylation.
Cheung
A
A
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin--Madison 53706.
Suttie
J W
JW
D000818:Animals; D019735:Carbon-Carbon Ligases; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D015394:Molecular Structure; D051381:Rats; D013379:Substrate Specificity; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism
D014812:Vitamin K; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase