Farnesol is utilized for protein isoprenylation and the biosynthesis of cholesterol in mammalian cells.
Evidence has been obtained indicating that free farnesol (F-OH) can be utilized for isoprenoid biosynthesis in mammalian cells. When rat C6 glial cells and an African green monkey kidney cell line (CV-1) were incubated with [3H]F-OH, radioactivity was incorporated into cholesterol, ubiquinone (CoQ) and isoprenylated proteins. The incorporation of label from [3H]F-OH into cholesterol in C6 and CV-1 cells was blocked by squalestatin 1 (SQ) which specifically inhibits the conversion of farnesyl pyrophosphate (F-P-P) to squalene. This result strongly suggests that cholesterol, and probably CoQ and protein, is metabolically labeled via F-P-P. SDS-PAGE analysis of the delipidated protein fractions from C6 and CV-1 cells revealed several labeled polypeptides. Consistent with these proteins being modified by isoprenylation of cysteine residues. Pronase E digestion released a major labeled product with the chromatographic mobility of [3H]farnesyl-cysteine (F-Cys). A different set of polypeptides was labeled when C6 and CV-1 cells were incubated with [3H]geranylgeraniol (GG-OH). Both sets of proteins appear to be metabolically labeled by [3H]mevalonolactone, and [3H]-labeled F-Cys and geranylgeranyl-cysteine (GG-Cys) were liberated from these proteins by Pronase E treatment. These cellular and biochemical studies indicate that F-OH can be used for isoprenoid biosynthesis and protein isoprenylation in mammalian cells after being converted to F-P-P by phosphorylation reactions that remain to be elucidated.
Crick
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Department of Biochemistry, University of Kentucky, College of Medicine, Lexington 40536, USA.
Andres
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Waechter
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CJ
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000096:biosynthesis*; D003545:Cysteine; D004224:Diterpenes / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005204:Farnesol / Q000378:metabolism*; D005910:Glioma; D007700:Kinetics; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014176:Protein Biosynthesis; D017368:Protein Prenylation; D011506:Proteins / Q000302:isolation & purification; D051381:Rats; D014316:Tritium; D014407:Tumor Cells, Cultured; D014451:Ubiquinone / Q000096:biosynthesis
D004224:Diterpenes; D009363:Neoplasm Proteins; D011506:Proteins; D014316:Tritium; D014451:Ubiquinone; D005204:Farnesol; C015367:mevalonolactone; D002784:Cholesterol; C017338:geranylgeraniol; D003545:Cysteine; D008798:Mevalonic Acid