1. Chapter 26 Lipids 4

2. 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.

3. 26.1 Acetyl Coenzyme A 4

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

5. 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.

6. 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

7. 26.2 Fats, Oils, and Fatty Acids4

8. 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.

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

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

11. 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

12. 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.

13. 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

14. 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

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

16. 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

17. 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

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

19. 26.3 Fatty Acid Biosynthesis4

20. 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).

21. 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

22. 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

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

24. 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

25. 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

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

27. 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

28. 26.4 Phospholipids 4

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

30. 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

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

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

33. 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

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

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

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

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

38. 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

39. 26.5 Waxes 4

40. 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.

41. 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

42. 26.6 Prostaglandins 4

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

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