Phosphorylation of farnesol in rat liver microsomes: properties of farnesol kinase and farnesyl phosphate kinase.
As farnesol may serve as a nonsterol endogenous regulator of the mevalonate pathway, the possibility that a kinase specific for its phosphorylation is present in the rat liver was investigated. In the 10,000 g supernatant of rat liver, farnesyl monophosphate was synthesized in the presence of ATP. The Km value for farnesol was 2.3 microM. Various detergents inhibited the activity of the enzyme. The farnesol kinase was present in rough and in smooth I microsomes, but not in smooth II microsomes, mitochondria, peroxisomes, Golgi, or plasma membranes. The enzyme was associated with the inner, luminal surface of the vesicles. Further analyses have demonstrated that an enzymatic mechanism exists which catalyzes the phosphorylation of farnesyl-P to farnesyl-PP. Activity of the farnesyl phosphate kinase resulted in the phosphorylation of the monophosphate by CTP but not by ATP, GTP, or UTP. This enzyme is activated by low concentrations of detergents. Treatment with proteases and chemical probes indicate that this second phosphorylation reaction probably takes place on the outer, cytoplasmic surface of microsomal vesicles. These results demonstrate that rat liver microsomes contain two enzymes for the consecutive phosphorylation of farnesol to farnesyl-PP.
Bentinger
M
M
Department of Biochemistry, Stockholm University, Sweden.
Grünler
J
J
Peterson
E
E
Swiezewska
E
E
Dallner
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005204:Farnesol / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes
D002413:Cations, Divalent; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C059195:farnesyl monophosphate; D005204:Farnesol; C004808:farnesyl pyrophosphate; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C112478:farnesol kinase; D017856:Phosphotransferases (Phosphate Group Acceptor); C112479:farnesyl phosphate kinase