Isopentenoid synthesis in isolated embryonic Drosophila cells. Farnesol catabolism and omega-oxidation.
Kc cells divert minimally 40% of their mevalonate carbon to n-fatty acids and unidentified compounds covalently linked to macromolecules (Havel, C., Rector, E. R., II, and Watson, J. A. (1986) J. Biol. Chem. 261, 10150-10156). Furthermore mevalonate carbon diversion appears to occur at the polyprenyl 1-pyrophosphate level. This report summarizes initial efforts to define the mevalonate carbon diversion pathway. We demonstrate that Kc cell extracts readily metabolize [14C]farnesyl 1-pyrophosphate and [14C]farnesol, via common intermediates, to identical 14C-products. Two of the major 14C-products were identified as trans,trans-3,7,11-trimethyl-2,6,10-dodecatrien-1,12-dioic acid and trans-3,7-dimethyl-2,6-decadien-1,10-dioic acid. Similar acids were also synthesized by supplemented rat liver extracts incubated with [14C]farnesol. We conclude that (a) mevalonate carbon diversion at the level of polyprenyl 1-pyrophosphate is a viable metabolic strategy, (b) polyprenols are oxidized to alpha,omega-prenyl dicarboxylic acids which are catabolized from the omega-terminus, and (c) this metabolic process is not limited to insect cells.
Gonzalez-Pacanowska
D
D
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Arison
B
B
Havel
C M
CM
Watson
J A
JA
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000378:metabolism*; D005204:Farnesol / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes
D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D005204:Farnesol; C004808:farnesyl pyrophosphate; D008798:Mevalonic Acid