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• Terpenes: Isoprene Units, Classification, Variations Lipids • Terpenes: isoprene units, classification, variations • Isopentenyl pyrophosphate biosynthesis from acetate general reactivity • C-C bond formation in terpene biosynthesis carbocation intermediate, extension, synthesis higher terpenes, synthesis cyclic structures • Cholesterol configuration, structure, biosynthesis, intermediate for: vitamin D, bile acids, corticosteroids, sex hormones • Carotenoids Steroids C D A B H H H HO cholesterol From diet, but can also synthesize from… acetate!! Terpenes: The Isoprene Rule Terpenes and terpenoids are the most important constituents in essential oils Terpenes are built from C5 isoprene units CH3 C CH2 = H2C C H Isoprene (2-methyl-1,3-butadiene) Isoprene units are linked head-to-tail tail head Terpenes are repeating isoprene units Classified according to the number of isoprene units they contain Class # Isoprene units # C atoms Monoterpene 2 10 Sesquiterpene 3 15 Diterpene 4 20 Sesterpene 5 25 Triterpene 6 30 Tetraterpene 8 40 Terpenes may be substituted, cyclic, or linked tail-to-tail OH Farnesol (terpenoid) OH Limonene Menthol (from lemon or orange oil) (from peppermint) OH Selinene Vitamin A (from celery oil) tail tail Squalene (from shark liver oil) Isopentenyl pyrophosphate Isoprenoid compounds are synthesized from acetate!! Early steps are analogous to fatty acid biosynthesis except no ACP O O O + SCoA -O SCoA Acetyl Malonyl coenzyme A coenzyme A O O + CO2 SCoA + CoASH Acetoacetyl coenzyme A O O O + SCoA SCoA Acetoacetyl Acetyl coenzyme A coenzyme A OH O SCoA OH + CoASH O 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) Enzymatic reduction OH O OH OH HO OH HO O Mevalonic acid Isopentenyl pyrophosphate: The biological isoprene unit O Enzymatic O phosphorylation O O - - O OPOPOH O OH 2-O PO HO 3 OHOH Mevalonate 3- - PO4 - CO2 CH3 O O H2C CCH2CH2OPOPOH OPP OHOH Isopentenyl pyrophosphate Enz-H isopentenyl diphosphate isomerase OPP OPP H H + Enz-H Enz Dimethylallyl Carbocation intermediate pyrophosphate Structurally similar but different chemical reactivity Isopentenyl Dimethylallyl pyrophosphate pyrophosphate (reactive C=C) (reactive allylic C) E+ Nu OPP OPP good leaving group C-C in Terpene Biosynthesis 10-C cation is the same whether 1 step or 2 steps + OPP OPP OPP + OPP pyrophosphate ion - [ OPP] OPP OPP OPP 10-C intermediate undergoes typical carbocation reactions OPP H H Enz- OPP Geranyl pyrophosphate (allylic pyrophosphate) H2O OH Geraniol (monoterpene in rose oil) OPP Geranyl pyrophosphate Enz OPP OPP 15-C carbocation [deprotonation] OPP Farnesyl pyrophosphate H2O OH Geranyl Farnesol geraniol Higher terpenes formed from coupling of terpenes via another mechanism, not successive addition of C5 units 2 OPP Farnesyl pyrophosphate Triterpene C30 (tail to tail coupling) Steroids t. n a io c t . a z iz n r E e m o intramolecular is OPP attack OPP "E" "Z" - H+ Limonene OH 3o carbocation H2O - H+ + -pinene -pinene bicyclic carbocation figure 26.6 capture by H2O and rearrangement Summary Terpene and steroid biosynthetic paths Monoterpenes Geranyl pyrophosphate (C10) (C10-pyrophosphate) 3-methyl-3-butenyl pyrophosphate Sesquiterpenes Farnesyl pyrophosphate Squalene (C15) (C15-pyrophosphate) (C30) 3-methyl-3-butenyl pyrophosphate Diterpenes C20-Pyrophosphate Lanosterol (C20) Tetraterpenes Cholesterol (C40) (a steroid) Steroids: Cholesterol C D A B CH3 CH3 R C D AB 5 H H 5 series (trans) CH3 CH3 R C D B H 5 H A 5 series (cis) • The most abundant steroid in humans • All other steroids arise from cholesterol H H H HO Cholesterol • The average adult has >200g • It is in almost all body tissues • Animals acquire cholesterol from their diet, but can synthesize all they need from acetate Synthesis from acetate Squalene O2, NADH monooxygenase O epoxide ring opening carbocation reactions * p. 1133 H H H HO Cholesterol Cholesterol is a precursor to other lipids Steroids Reactions Vitamin D Cholesterol Sex hormones Bile acids Corticosteroids Vitamin D From enzymatic oxidation of cholesterol to 7-dehydrocholesterol Present in skin and converted to vitamin D by sunlight Important in Ca2+ absorption sunlight HH HO 7-Dehydrocholesterol HH HO Vitamin D3 Bile Acids Bile salts: amide derivatives Bottom face polar; top face non-polar Emulsify fats by forming micelles where fats on inside and bile salts on outside FAT salts O H O X 2 OH H H H HO H OH X = OH; Cholic Acid X = NHCH2CH2SO3Na; Sodium taurocholate (bile salt) Micelle fig. from Mol. Cell. Biol. Corticosteroids Many physiological effects, ie. maintain electrolyte balance; regulate carb, lipid, protein metabolism; mediate allergic and inflammatory response Cortisol most abundant Cortisone – antiinflammatory drug OH O HO OH H OH H H O O O OH Cortisol H H H O Cortisone Sex hormones Regulate biological processes • Male – androgens (testes) • Female – estrogens (ovaries) • Pregnancy – progestins O Cholesterol H H H O Progesterone OH OH H H H H H H O HO Testosterone Estradiol Carotenoids Tetraterpenes; conjugated π-system Color: flowers, fruit, plants, insects, animal Tail-to-tail linkage between 2-C20 units 100 million tons carotenoids bio- synthesized from acetate per year Lycopene (tomatoes) H H -Carotene (carrots).
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