Chapter 24: Lipids. Hydrophobic (non-polar, soluble in organic

Chapter 24: Lipids. Hydrophobic (non-polar, soluble in organic

Chapter 24: Lipids. Hydrophobic (non-polar, soluble in organic solvent), typically of low molecular compound of organic origin fatty acids and waxes essential oils many vitamins hormones (non-peptide) components of cell membranes (non-peptide) Share a common biosynthesis that ultimately derives their carbon source from glucose (glycolysis) Glucose pyruvate lactate

1 24.1: Acetyl Coenzyme A. AcSCoA is a thioester. R= H, HSCoA R= acetyl, AcSCoA Fig 24.1, p. 1076 Pyruvate dehydrogenase: Multi-enzyme complex that converts pyruvate to AcSCoA.

_ 2 Acetyl CoA is a thioester. Thioesters are more reactive toward nucleophilic acyl substitution than esters, but considerably less reactive than acid chlorides and anhydrides. Thioester enolize more readily than esters. The enol can react with electrophile to afford -substitution products

3 24.2: Fats, Oils, and Fatty Acids. Fatty acids: refers to long, straight-chain saturated and unsaturated acids, typically from C12 - C20 (Table 24.1, p. 1079). saturated fatty acids: CH3(CH2)nCO2H n=10, lauric acid (C12) n=12, myristic acid (C14) n=14, palmitic acid (C16)

n=16, steric acid (C18) unsaturated fatty acid C18, oleic acid 3 polyunsaturated fatty acids (PUFA) 6 C18, linolenic acid (18:3)

6 C18, linoleic acid (18:4) 4 C20, arachidonic acid (20:4) Fats and Oils: Triglycerides (triaceylglycerols) are tri-esters of glycerol (1,2,3-trihydroxypropane) and fatty acids. The R groups can be saturated or unsaturated, the same or different

5 Soaps: sodium & potassium salts of fatty acid produced from the saponification (base hydrolysis) of animal fats (glycerides) Soaps have a hydrophilic, polar head group (carboxylate salt) and a hydrophobic, non-polar tail (Ch. 18.7). Fatty acid amides (FAA): 6

24.3: Fatty Acid Biosynthesis. Fatty acid biosynthesis is performed by a cluster of discrete enzymes in bacteria, and a very large multi-protein assembly in animals (fatty acid synthase, FAS). The fatty acid is attached to an acyl carrier protein (ACP), while other proteins perform an iterative two-carbon chain extension reaction that will yield the fatty acid. 7 Fatty acid synthase chain extension reaction (mechanism p. 1082):

Ketosynthase (KS) C2 8 Ketoreductase (KR): NADPH (nicotinamide adenine diphosphate phosphate) is a nucleophilic hydride (H) donor (reducing agent) = H Dehydratase (DH):

-H2O Enoyl Reductase (ER) C4 9 Iterative two-carbon chain extension C6

C8 10 Thioesterase (TE) 24.4 Phospholipids. 11

Glycerophospholipids are important components of cell membranes. Nonpolar tails aggregate in the center of a bilayer ionic head is exposed to solvent. Phosphatidylcholine (lechtins) 24.5: Waxes. esters of long chain fatty acids (C16 - C36) with long chain alcohols (C24 - C36) CH3(CH2)nCO2(CH2)nCH3 12

24.6: Prostaglandins. (eicosanoids) C20 compounds derived from arachidonic acid and related fatty acids hormone: (Greek, horman, to set in motion) chemical messengers from one cell to another, that acts as a signal for a biochemical event. 13 Prostaglandin biosynthesis:

COX-2 Tyr-385 Ser-385 14 COX-1 is a constitutive enzyme that is expressed in virtually all mammalian cells COX-2 is an inducible enzyme that is expressed as a results of a biochemical response; expressed in phagocytes (macrophages) as part of an inflammation response.

NSAIDs: non-steroidal anti-inflammatory drugs Aspirin, ibuprofren, and naproxen are non-selective inhibitors of COX Celebrex, vioxx, and brextra are selective inhibitors of COX-2 (coxibs) 15 Thromboxanes: named for their role in thrombosis, the formation of a clot inside a blood vessel

H2O Leukotrienes 16 24.7: Terpenes: The Isoprene Rule. Isoprenoids- C10 (terpenes), C15 (sesquiterpenes) and C20 (diterpenes) plant; essential oils Ruzicka isoprene rule: terpenoids are derived from isoprene isoprene units (C5)

(2-methyl-1,3-butadiene) 17 The precursor to C10 terpenoids (monoterpenes) is geraniol diphosphate (diphosphate), which consists of two C5 isoprene units that are joined head-to-tail head tail

PP = head - tail head - tail C15 sesquiterpenoids are derived from farnesyl diphosphate, which consists of three C5 isoprene units that are joined head-to-tail C20 diterpenoids are derived from geranylgeranyl diphosphate, which consists of four C5 isoprene units that are joined head-to-tail 18

C25 sesterpenoids are derived from geranylfarnesyl diphosphate, which consists of five C5 isoprene units that are joined head-to-tail C30 triterpenoids and steroids are derived from squalene, which consists of two C15 farnesyl units that are joined tail-to-tail C40 tetraterpenoids are derived from phytocene, which consists of two C20 geranylgeranyl units that are joined tail-to-tail

19 b-carotene 20 24.8: Isopentyl Diphosphate: The Biological Isoprene Unit. Mevalonic acid is the biosynthetic precursor to the actual C5 isoprene units, which are isopentyl diphosphate (IPP, tail) and dimethylallyl diphosphate (DMAPP, head) 24.10: The Pathway from Acetate to Isopentenyl Diphosphate.

Mevalonate Pathway 21 Conversion of mevalonic acid to IPP and DMAPP 24.9: Carbon-Carbon Bond Formation in Terpene Biosynthesis. Conversion of IPP and DMAPP to geranyl-PP and farnesyl-PP nucleophilic tail group

electrophilic head group electrophilic head group nucleophilic tail group 22

Conversion of gernanyl-PP to monoterpenes Limonene & -TerpineolTerpineol limonene C=C bond acts as a nucleophile -terpineol 23

24.11: Steroids: Cholesterol Cholesterol biosynthesis (mechanism: p. 1100) part a: the cyclization 24 Cholesterol biosynthesis, part b: the 1,2-shifts 25

24.12: Vitamin D. (please read) 24.13: Bile Acids. (please read) 24.14: Corticosteroids. (please read) 26 24.15: Sex hormones - (please read) Androgens: male (slugs and snails, and puppy-Terpineoldogs' tails) Estrogens: female (sugar and spice and everything nice)

24.16: Carotenoids - derived from phytocene (C40) (please read) Lycopene 27 b-carotene

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