Chapter 26 Lipids 4

Lipids Lipids are naturally occurring substances grouped together on the basis of a common property—they are more soluble in nonpolar solvents than in water. Some of the most important of them—the ones in this chapter—are related in that they have acetic acid (acetate) as their biosynthetic origin. In many biosynthetic pathways a substance called acetyl coenzyme A serves as the source of acetate.

26.1 Acetyl Coenzyme A 4

Structure of Coenzyme A R = H; Coenzyme A R = CCH3; Acetyl coenzyme A O

Reactivity of Coenzyme A Nucleophilic acyl substitution CH3CSCoA O CH3C O HY • • Y • • + HSCoA Acetyl coenzyme A is a source of an acetyl group toward biological nucleophiles; it is an acetyl transfer agent.

Reactivity of Coenzyme A can react via enol CH3CSCoA O CSCoA OH H2C E+ Acetyl coenzyme A reacts with biological electrophiles at its a carbon atom. CH2CSCoA O E

26.2 Fats, Oils, and Fatty Acids 4

Fats and Oils RCOCH CH2OCR' O CH2OCR" Fats and oils are naturally occurring mixture of triacylglycerols (also called triglycerides). Fats are solids; oils are liquids.

Fats and Oils CH3(CH2)16COCH CH2OC(CH2)16CH3 O Tristearin; mp 72°C

Fats and Oils CH2OC(CH2)16CH3 O CH2(CH2)6COCH C H CH3(CH2)6CH2 2-Oleyl-1,3-distearylglycerol; mp 43°C

2-Oleyl-1,3-distearylglycerol mp 43°C Fats and Oils 2-Oleyl-1,3-distearylglycerol mp 43°C H2, Pt Tristearin mp 72°C

Fatty Acids O R'COCH CH2OCR CH2OCR" O HOCR O R'COH HOCH CH2OH H2O O Acids obtained by the hydrolysis of fats and oils are called fatty acids. Fatty acids usually have an unbranched chain with an even number of carbon atoms. If double bonds are present, they are almost always cis.

Table 26.1 (p 1018) Systematic name Common name O CH3(CH2)10COH Dodecanoic acid Lauric acid O CH3(CH2)12COH Tetradecanoic acid Myristic acid O CH3(CH2)14COH Hexadecanoic acid Palmitic acid

Table 26.1 (p 1018) Systematic name Common name O CH3(CH2)16COH Octadecanoic acid Stearic acid O CH3(CH2)18COH Icosanoic acid Arachidic acid

Table 26.1 (p 1018) O C H CH3(CH2)7 (CH2)7COH Systematic name: (Z)-9-Octadecenoic acid Common name: Oleic acid

Table 26.1 (p 1018) C H CH3(CH2)4 O (CH2)7COH CH2 Systematic name: (9Z, 12Z)-9,12-Octadecadienoic acid Common name: Linoleic acid

Table 26.1 (p 1018) C H O (CH2)7COH CH2 CH3CH2 Systematic name: (9Z, 12Z, 15Z)-9,12,15- Octadecatrienoic acid Common name: Linolenic acid

Table 26.1 (p 1018) H OH O Systematic name: (5Z, 8Z, 11Z, 14Z)-5,8,11,14- Icosatetraenoic acid Common name: Arachidonic acid

26.3 Fatty Acid Biosynthesis 4

Fatty Acid Biosynthesis Fatty acids are biosynthesized via acetyl coenzyme A. The group of enzymes involved in the overall process is called fatty acid synthetase. One of the key components of fatty acid synthetase is acyl carrier protein (ACP—SH).

Fatty Acid Biosynthesis An early step in fatty acid biosynthesis is the reaction of acyl carrier protein with acetyl coenzyme A. CH3CSCoA O CH3CS—ACP O + HS—ACP + HSCoA

Fatty Acid Biosynthesis A second molecule of acetyl coenzyme A reacts at its a carbon atom with carbon dioxide (as HCO3–) to give malonyl coenzyme A. CH3CSCoA O OCCH2CSCoA O – HCO3 – + Acetyl coenzyme A Malonyl coenzyme A

Fatty Acid Biosynthesis Malonyl coenzyme A then reacts with acyl carrier protein. OCCH2CS—ACP O – OCCH2CSCoA O – ACP—SH Malonyl coenzyme A

Fatty Acid Biosynthesis Malonyl—ACP and acetyl—ACP react by carbon-carbon bond formation, accompanied by decarboxylation. O CH2CS—ACP O CH3C CH3C S—ACP CH2CS—ACP O – C •• • • S-Acetoacetyl—ACP

Fatty Acid Biosynthesis In the next step, the ketone carbonyl is reduced to a secondary alcohol. CH2CS—ACP O CH3C OH H CH2CS—ACP O CH3C NADPH S-Acetoacetyl—ACP

Fatty Acid Biosynthesis The alcohol then dehydrates. CH2CS—ACP O CH3C OH H CHCS—ACP O CH3CH

Fatty Acid Biosynthesis Reduction of the double bond yields ACP bearing an attached butanoyl group. Repeating the process gives a 6-carbon acyl group, then an 8-carbon one, then 10, etc. CH3CH2CH2CS—ACP O CHCS—ACP O CH3CH

26.4 Phospholipids 4

Phospholipids Phospholipids are intermediates in the biosynthesis of triacylglycerols. The starting materials are L-glycerol 3-phosphate and the appropriate acyl coenzyme A molecules.

CH2OPO3H2 CH2OH H HO RCSCoA O R'CSCoA O + + The diacylated species formed in this step is called a phosphatidic acid. CH2OPO3H2 CH2OCR H R'CO O

The phosphatidic acid then undergoes hydrolysis of its phosphate ester function. CH2OPO3H2 CH2OCR H R'CO O

CH2OH CH2OCR H R'CO O Reaction with a third acyl coenzyme A molecule yields the triacylglycerol. H2O CH2OPO3H2 CH2OCR H R'CO O

CH2OH CH2OCR H R'CO O Reaction with a third acyl coenzyme A molecule yields the triacylglycerol. R"CSCoA O CH2OCR" CH2OCR H R'CO O

Phosphatidylcholine Phosphatidic acids are intermediates in the formation of phosphatidylcholine. CH2OPO3H2 CH2OCR H R'CO O CH2OPO2 CH2OCR H R'CO O – (CH3)3NCH2CH2O +

Phosphatidylcholine CH2OPO2 CH2OCR H R'CO O – (CH3)3NCH2CH2O + hydrophobic "tail" hydrophobic "tail" polar "head group"

hydrophobic (lipophilic) "tails" Phosphatidylcholine hydrophobic (lipophilic) "tails" hydrophilic "head group"

Cell Membranes water Cell membranes are "lipid bilayers." Each layer has an assembly of phosphatidyl choline molecules as its main structural component. water

Cell Membranes water The interior of the cell membrane is hydrocarbon-like. Polar materials cannot pass from one side to the other of the membrane. water

26.5 Waxes 4

Waxes Waxes are water-repelling solids that coat the leaves of plants, etc. Structurally, waxes are mixtures of esters. The esters are derived from fatty acids and long-chain alcohols.

Waxes Waxes are water-repelling solids that coat the leaves of plants, etc. Structurally, waxes are mixtures of esters. The esters are derived from fatty acids and long-chain alcohols. CH3(CH2)14COCH2(CH2)28CH3 O Triacontyl hexadecanoate: occurs in beeswax

26.6 Prostaglandins 4

Prostaglandins Prostaglandins are involved in many biological processes. Are biosynthesized from linoleic acid (C18) via arachidonic acid (C20). (See Table 26.1)

Examples: PGE1 and PGF1a O HO OH PGE1 HO OH O PGF1a