Biosynthesis of prenyl diphosphates by cell-free extracts from mammalian tissues.
When assayed by the conventional method for prenyltransferase using a combination of [1-14C]isopentenyl and geranyl diphosphates, 100,000 x g supernatants of homogenates of rat liver and brain catalyzed the formation of geranylgeranyl diphosphate at a much lower rate than that of farnesyl diphosphate. Surprisingly, however, the formation of geranylgeranyl diphosphate in incubations of [1-14C]isopentenyl diphosphate alone with these enzyme systems was comparable to that of farnesyl diphosphate. Addition of dimethylallyl diphosphate to the same enzyme systems in the presence of [1-14C]isopentenyl diphosphate resulted in a marked increase in the rate of formation of farnesyl diphosphate, while the rate of formation of geranylgeranyl diphosphate was saturated. Metabolic labeling of rat liver and kidney slices with [5-3H]mevalonic acid revealed that the major prenyl residue of the detectable prenylated proteins was actually the geranylgeranyl group. Coupled with the previous finding that geranylgeranyl diphosphate accumulates during metabolic labeling of rat liver slices with [2-3H]mevalonic acid [Sagami, H., Matsuoka, S., and Ogura, K. (1991) J. Biol. Chem. 266, 3458-3463], these results indicate that the rate of de novo synthesis of geranylgeranyl diphosphate from mevalonic acid is comparable to that of farnesyl diphosphate.
Sagami
H
H
Institute for Chemical Reaction Science, Tohoku University, Sendai.
Korenaga
T
T
Kurisaki
A
A
Ogura
K
K
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004122:Dimethylallyltranstransferase / Q000032:analysis / Q000378:metabolism*; D045782:Hemiterpenes; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009943:Organophosphorus Compounds / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes
D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004809:isopentenyl pyrophosphate; C004808:farnesyl pyrophosphate; D004122:Dimethylallyltranstransferase; C002963:geranylgeranyl pyrophosphate