Naturally occurring compounds that are typically of low molecular weight and are hydrophobic (soluble in organic solvent).

Transcription

1 hapter 27. Biomolecules: Lipids aturally occurring compounds that are typically of low molecular weight and are hydrophobic (soluble in organic solvent). fatty acids and waxes essential oils many vitamins hormones (non-peptide) components of cell membranes (non-peptide) : Waxes, fats and oils Fatty acids: refers to long, straight-chain saturated and unsaturated acids, typically from saturated fatty acids: 3 ( 2 ) n 2 n=10, lauric acid n=12, myristic acid n=14, palmitic acid n=16, steric acid unsaturated fatty acid 2 18, oleic acid polyunsaturated fatty acids (PUFA) , linolenic acid (18:3) 18, linoleic acid (18:4) 20, arachidonic acid (20:4)

2 Fatty acid amides (FAA): Arachidonic Acid ( 20 ) Waxes: esters of long chain fatty acids ( ) with long chain alcohols ( ) tetrahydrocannabinol 3 ( 2 ) n 2 ( 2 ) n 3 Fats and ils: Triacylglcerols (triglycerides), fatty acid ( ) esters of glycerol, 2 -()- 2. glycerol fatty acids Soap sodium & potassium salts of fatty acid produced from the saponification (base hydrolysis) of animal fats (glycerides) 2 2 n n n a 3 n Soaps have a hydrophilic, polar head group (carboxylate salt) and a hydrophobic, non-polar tail. In aqueous solution they form a micelle structure in which the soap molecules orient so that the the hydrophobic tail cluster in the middle of the micelle where their interaction with water is minimized; the polar carboxylate groups are on the solvent exposed outside of the micelle. a

3 Micelle: Steric acid dodecylphosphocholine (DP) P polar head group hydrophobic tail Phospholipids: diesters of phosphoric acid ( 3 P 4 ) Glycerophospholipids: structurally related to a triglyceride glycerol backbone and two fatty acid ester unsaturated 2 2 P saturated 2 2 ( 3 ) 3 Phosphatidylcholine (lechtins) (L-configuration) unsaturated 2 2 P saturated Phosphatidylethanolamine (cephalins) (L-configuration)

4 Glycerophospholipids are important components of cell membranes onpolar tails aggregate in the center of a bilayer Ionic head is exposed to solvent ell membranes are on the order of 50 Å (5 nm) thick Sphingomyelins: P 2 2 ( 3 ) 3 ( 2 ) n 3 ( 2 ) 12 3 sphingosine ( 2 ) 12 3 sphingomyelin Prostaglandins (eicosanoids): 20 compounds derived from arachidonic acid and related fatty acids hormone: (Greek, horman, to set in motion) chemical messenger from one cell to another, that acts as a signal for a biochemical event. phospholipid 2 Arachidonic acid 2 prostaglandin endoperoxide reductase prostaglandin (PG) synthase, prostacyclin (PGI) synthase 2 Prostaglandin F 2! prostaglandin endoperoxide D isomerase Prostaglandin 2 (PG 2 ) prostaglandin endoperoxide E isomerase Prostaglandin I 2 (Prostacyclin) 2 2 Prostaglandin D 2 Prostaglandin E

5 Prostaglandin biosynthesis 2 prostaglandin synthase cyclooxygenase (X-1 or X-2) 2 2 Arachidonic acid PG2 PGG2 Tyr then e, PGG Structure of X-2 cell membrane 2 Tyr-385 Ser-530 Ser-530 X acetylsalicylic acid covalently modified enzyme

6 Thromboxanes: named for their role in thrombosis, the formation of a clot inside a blood vessel PG 2 thromboxane synthase 2 2 Thromboxane A 2 Thromboxane B 2 Leukotrienes 2 Lipoxygenase 2 eme, Aracidonic acid Leukotriene A S 2 2 Leukotriene D X-1 is a constitutive enzyme that is expressed in virtually all mammalian cells X-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. SAIDs: non-steroidal anti-inflammatory drugs Aspirin, ibuprofren, and naproxen are non-selective inhibitors of X Ac 3 elebrex, vioxx, and brextra are selective inhibitors of X-2 (oxibs) S 2 S 2 S 2 F

7 27.5 Terpenoids (isoprenoids): 10, 15 and 20 plant essential oils uzicka isoprene rule: terpenoids are derived from isoprene units ( 5 ) isoprene (2-methyl-1,3-butadiene) amphour ()-arvone (caraway seeds) (-)-arvone (spearmint) ()-limonene (oranges) (-)-limonene (lemons) !-pinene "-pinene patchouli alcohol (patchouli oil) 2 hryanthemic acids Grandisol 404 The precursor to 10 terpenoids (monoterpenes) is geraniol pyrophosphate (diphosphate), which consists of two 5 isoprene units that are joined head-to-tail head tail PP = P PP head - tail head - tail P 15 sesquiterpenoids are derived from farnesyl pyrophosphate, which consists of three 5 isoprene units that are joined head-to-tail 20 diterpenoids are derived from geranylgeranyl pyrophosphate, which consists of four 5 isoprene units that are joined head-to-tail PP PP

8 25 sesterpenoids are derived from geranylfarnesyl pyrophosphate, which consists of five 5 isoprene units that are joined head-to-tail 30 triterpenoids and steroids are derived from squalene, which consists of two 15 farnesyl units that are joined head-to-head PP 40 tetraterpenoids are derived from phytocene, which consists of two 20 geranylgeranyl units that are joined head-to-head cedrane 2 Gibberellic acid Lanosterol Lycopene!-carotene

9 27.6 Biosynthesis of Terpenoids Mevalonic acid is the biosynthetic precursor to the actual 5 isoprene units, which are isopentyl pyrophosphate (IPP, tail) and dimethylallyl pyrophosphate (DMAPP, head) Mevalonate Pathway B: 2 SoA acetyl oa Enzyme-ys-S 3 SoA!-ketoacyl thiolase 2 SoA 3 S-ys-Enzyme laisen condensation E-ys-S SoA SoA acetoacetyl oa acetyl oa 2 oas = S P P oenzyme A P 408 B: 2 SoA acetyl oa MG-oA synthase B 2 SoA SoA acetoacetyl oa aldol condensation 3 2 SoA 3-ydroxy-3-methylglutaric acid (MG-oA) MG-oA reductase 2 ADP 3 2 Mevalonic acid -B SoA ADP ADP ADP ADP 2 =, compactin = 3, mevinolin (Lovastatin) P P P 2-3 ADP 2 MG-oA reductase inhibitors holesterol lowering agents

10 onversion of mevalonic acid to IPP and DMAPP ATP 3 2 Mevalonic acid AMP 3 P - P - - ATP ADP 3 P 2-3 P - P P 4 3- B: 3 P - P - - B: P - P - - rearrangment P - P - - isopentenyl-pp (IPP) dimethylallyl-pp (DMAPP) onversion of IPP and DMAPP to geraniol-pp and farnesyl-pp electrophilic head group DMAPP PP - PP Mg 2 PP B: IPP PP nucleophilic tail group PP geranyl pyrophosphate ( 10 ) - PP Mg 2 PP PP electrophilic head group PP B: nucleophilic tail group farnesyl pyrophosphate ( 15 ) 410 PP PP squalene synthase onversion of genanyl-pp to monoterpenes Limonene: PP PP PP an not cyclize Linallyl-PP PP - = bond acts as a nucleophile :B limonene

11 α-terpineol PP PP 2 Linallyl-PP Problem 27.8a (hint) "-pinene!-pinene arbocation rearrangements: 1,2-hydride shift 2 terpinen-4-ol thujone Steroids ing designation and numbering Adenocortical: metabolic hormones (please read) Sex hormones: (please read) androgens (male) Testosterone Androsterone estrogens (female) Androstenedione dianabol Estrone Estradiol Synthetic steroids (please read) Progesterone Ethynylestradiol

12 27.8 Stereochemistry of steroids stereochemistry of the ring fusion (two rings that share a common - bond) decalin: two fused cyclohexanes ( 10 ) trans-decalin: cis-decalin 414 The A-B ring fusion of steroids can be either cis or trans (most commonly trans) The B and D ring fusions are usually trans 3 3 Dihydrotestosterone 2 holic acid

13 27.9 holesterol biosynthesis (figure 27.6, pages ) part a: the cyclization Squalene epoxidase eme, 2 Squalene ( ) A Squalene xide ( ) Squalene cyclase Protosterol cation 416 holesterol biosynthesis, part b: the 1,2-shifts Protosterol cation ( ) 1,2-hydride shift ,2-hydride shift ,2-methyl shift ,2-methyl shift B: Lanosterol ( ) Lanosterol ( ) holesterol ( )