26. 10 The Pathway from Acetate to isopentenyl Pyrophosphate Ho O CH3CCH, CSCoA CHiCSCoa-> CH3 CCH,CSCOA OASH CH,COH Acetoacetyl Acetyl 3-Hydroxy-3-methylglt A coenzyme A(HMG The product of this reaction, 3-hydroxy-3-methylglutaryl coenzyme A(HMG CoA), has the carbon skeleton of mevalonic acid and is converted to it by enzymatic reduction HO CH3CCH, CSCOA →CH3CCH2CH2OH act by inhibiting the enzyme that catalyzes this reactio CH,COH CH,COH 3-Hydroxy-3-methylglutaryl Mevalonic coenzyme A(HMG C In keeping with its biogenetic origin in three molecules of acetic acid, mevalonic acid has six carbon atoms. The conversion of mevalonate to isopentenyl pyrophosphate ivolves loss of the"extra"carbon as carbon dioxide. First, the alcohol hydroxyl groups of mevalonate are converted to phosphate ester functions--they are enzymatically phos phorylated, with introduction of a simple phosphate at the tertiary site and a pyro phate at the primary site. Decarboxylation, in concert with loss of the tertiary pho introduces a carbon-carbon double bond and gives isopentenyl pyrophosphate, the fun damental building block for formation of isoprenoid natural products H3C、cOPO3 3C CCH,CH,OPP H, CH, CH,OH C-CH CH,CH,OPP H,C Mevalonate (Unstable; undergoes Isopentenyl rapid decarboxylation pyrophosphate with loss of phosphate) Much of what we know concerning the pathway from acetate to mevalonate to isopentenyl pyrophosphate to terpenes comes from"feeding"experiments, in which plants are grown in the presence of radioactively labeled organic substances and the dis tribution of the radioactive label is determined in the products of biosynthesis. To illus- trate, eucalyptus plants were allowed to grow in a medium containing acetic acid enriched with C in its methyl group. Citronellal was isolated from the mixture of monoterpenes produced by the plants and shown, by a series of chemical degradations, the principal component of to contain the radioactive" C label at carbons 2. 4. 6. and 8. as well as at the carbons citronella oil and is used as of both branching methyl groups an insect repellent. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate 1033 The product of this reaction, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA), has the carbon skeleton of mevalonic acid and is converted to it by enzymatic reduction. In keeping with its biogenetic origin in three molecules of acetic acid, mevalonic acid has six carbon atoms. The conversion of mevalonate to isopentenyl pyrophosphate involves loss of the “extra” carbon as carbon dioxide. First, the alcohol hydroxyl groups of mevalonate are converted to phosphate ester functions—they are enzymatically phos￾phorylated, with introduction of a simple phosphate at the tertiary site and a pyrophos￾phate at the primary site. Decarboxylation, in concert with loss of the tertiary phosphate, introduces a carbon–carbon double bond and gives isopentenyl pyrophosphate, the fun￾damental building block for formation of isoprenoid natural products. Much of what we know concerning the pathway from acetate to mevalonate to isopentenyl pyrophosphate to terpenes comes from “feeding” experiments, in which plants are grown in the presence of radioactively labeled organic substances and the dis￾tribution of the radioactive label is determined in the products of biosynthesis. To illus￾trate, eucalyptus plants were allowed to grow in a medium containing acetic acid enriched with 14C in its methyl group. Citronellal was isolated from the mixture of monoterpenes produced by the plants and shown, by a series of chemical degradations, to contain the radioactive 14C label at carbons 2, 4, 6, and 8, as well as at the carbons of both branching methyl groups. HO CH3CCH2CH2OH O CH2COH Mevalonic acid HO O CH3CCH2CSCoA O CH2COH 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) O CH3CSCoA Acetyl coenzyme A HO O CH3CCH2CSCoA O CH2COH 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) O O CH3CCH2CSCoA Acetoacetyl coenzyme A CoASH Coenzyme A Some of the most effective cholesterol-lowering drugs act by inhibiting the enzyme that catalyzes this reaction. PO4 3 CO2 C O CH2 C H3C OH CH2CH2OH O Mevalonate H3C C CH2CH2OPP O CH2 O C OPO3 2 (Unstable; undergoes rapid decarboxylation with loss of phosphate) H2C CCH2CH2OPP H3C Isopentenyl pyrophosphate Citronellal occurs naturally as the principal component of citronella oil and is used as an insect repellent. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website