Vitamin K-dependent carboxylase: mRNA distribution and effects of vitamin K-deficiency and warfarin treatment.
A cDNA encoding vitamin K-dependent gamma-glutamyl carboxylase was cloned from a human Hep G2 cDNA library. The RNA transcript of the enzyme was found to be widely distributed in various human and rat tissues with liver showing the highest level. The carboxylase transcription in liver was not affected in rats treated with a single dose of warfarin (10 mg/kg) when measured up to 48 hours after the dose, though, at 12 hours, carboxylase activity measured in liver microsomes was elevated 5.4 fold over controls (p < 0.001). In rats fasted for 72 hours there was no affect on transcription in the liver while hepatic carboxylase activity increased 4.1 fold (p < 0.001). These data suggest that the increase in activity of the liver carboxylase in warfarin treated or fasted rats was not regulated by transcription but more likely was due to a posttranscriptional mechanism.
Liu
Y
Y
Clinical Pharmacology Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Nelson
A N
AN
Lipsky
J J
JJ
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D015152:Blotting, Northern; D019735:Carbon-Carbon Ligases; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D005215:Fasting; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008025:Ligases / Q000096:biosynthesis* / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014813:Vitamin K Deficiency / Q000201:enzymology*; D014859:Warfarin / Q000494:pharmacology*
D000199:Actins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014859:Warfarin; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase