1. Dr. Wolf's CHM 424 26- 1 Chapter 26 Lipids

2. Dr. Wolf's CHM 424 26- 2 LipidsLipids 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. Dr. Wolf's CHM 424 26- 3 26.1 Acetyl Coenzyme A

4. Dr. Wolf's CHM 424 26- 4 Structure of Coenzyme A R = H; Coenzyme A R = CCH 3 ; Acetyl coenzyme A O

5. Dr. Wolf's CHM 424 26- 5 Reactivity of Coenzyme A Nucleophilic acyl substitution CH 3 CSCoA O HYHYHYHY CH 3 C O Y + HSCoA Acetyl coenzyme A is a source of an acetyl group toward biological nucleophiles; it is an acetyl transfer agent.

6. Dr. Wolf's CHM 424 26- 6 Reactivity of Coenzyme A can react via enol CH 3 CSCoA O Acetyl coenzyme A reacts with biological electrophiles at its  carbon atom. CSCoA OH H2CH2CH2CH2C E+E+E+E+ CH 2 CSCoA OE

7. Dr. Wolf's CHM 424 26- 7 26.2 Fats, Oils, and Fatty Acids

8. Dr. Wolf's CHM 424 26- 8 Fats and Oils Fats and oils are naturally occurring mixture of triacylglycerols (also called triglycerides). Fats are solids; oils are liquids. RCOCH CH 2 OCR' O CH 2 OCR" OO

9. Dr. Wolf's CHM 424 26- 9 CH 3 (CH 2 ) 16 COCH CH 2 OC(CH 2 ) 16 CH 3 O OO Fats and Oils Tristearin; mp 72°C

10. Dr. Wolf's CHM 424 26- 10 Fats and Oils 2-Oleyl-1,3-distearylglycerol; mp 43°C CH 2 OC(CH 2 ) 16 CH 3 OO CH 2 (CH 2 ) 6 COCH O C H C H CH 3 (CH 2 ) 6 CH 2

11. Dr. Wolf's CHM 424 26- 11 Fats and Oils 2-Oleyl-1,3-distearylglycerol mp 43°C H 2, Pt Tristearin mp 72°C

12. Dr. Wolf's CHM 424 26- 12 O R'COCH CH 2 OCR O CH 2 OCR" O Fatty Acids 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. H2OH2OH2OH2O HOCH CH 2 OH OHOCR OR'COH OHOCR"

13. Dr. Wolf's CHM 424 26- 13 Table 26.1 O CH 3 (CH 2 ) 10 COH Dodecanoic acid Lauric acid Systematic name Common name O CH 3 (CH 2 ) 12 COH Tetradecanoic acid Myristic acid O CH 3 (CH 2 ) 14 COH Hexadecanoic acid Palmitic acid

14. Dr. Wolf's CHM 424 26- 14 Table 26.1 O CH 3 (CH 2 ) 16 COH Octadecanoic acid Stearic acid O CH 3 (CH 2 ) 18 COH Icosanoic acid Arachidic acid Systematic name Common name

15. Dr. Wolf's CHM 424 26- 15 Table 26.1 OC H C H CH 3 (CH 2 ) 7 (CH 2 ) 7 COH Systematic name: (Z)-9-Octadecenoic acid Common name: Oleic acid

16. Dr. Wolf's CHM 424 26- 16 Table 26.1 Systematic name: (9Z, 12Z)-9,12-Octadecadienoic acid Common name: Linoleic acid C H C H CH 3 (CH 2 ) 4 O (CH 2 ) 7 COH CH 2 C H C H

17. Dr. Wolf's CHM 424 26- 17 Table 26.1 Systematic name: (9Z, 12Z, 15Z)-9,12,15- Octadecatrienoic acid Common name: Linolenic acid C H C HO (CH 2 ) 7 COH CH 2 C H C H CH 3 CH 2 C H C H CH 2

18. Dr. Wolf's CHM 424 26- 18 Table 26.1 Systematic name: (5Z, 8Z, 11Z, 14Z)-5,8,11,14- Icosatetraenoic acid Common name: Arachidonic acid H HH H HH H H OHO

19. Dr. Wolf's CHM 424 26- 19 trans-Fatty Acids Are formed by isomerization that can occur when esters of cis-fatty acids are hydrogenated. O ORHOOR H H 2, cat

20. Dr. Wolf's CHM 424 26- 20OOR HOOR H H O ORH H 2, cat

21. Dr. Wolf's CHM 424 26- 21 26.3 Fatty Acid Biosynthesis

22. Dr. Wolf's CHM 424 26- 22 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).

23. Dr. Wolf's CHM 424 26- 23 Fatty Acid Biosynthesis An early step in fatty acid biosynthesis is the reaction of acyl carrier protein with acetyl coenzyme A. CH 3 CSCoA O+ HS—ACP CH 3 CS—ACP O+ HSCoA

24. Dr. Wolf's CHM 424 26- 24 Fatty Acid Biosynthesis A second molecule of acetyl coenzyme A reacts at its  carbon atom with carbon dioxide (as HCO 3 – ) to give malonyl coenzyme A. CH 3 CSCoA O+ HCO 3 – Acetyl coenzyme A OCCH 2 CSCoA O –O Malonyl coenzyme A

25. Dr. Wolf's CHM 424 26- 25 Fatty Acid Biosynthesis Malonyl coenzyme A then reacts with acyl carrier protein. OCCH 2 CSCoA O –O Malonyl coenzyme A ACP—SH OCCH 2 CS—ACP O –O

26. Dr. Wolf's CHM 424 26- 26 Fatty Acid Biosynthesis Malonyl—ACP and acetyl—ACP react by carbon-carbon bond formation, accompanied by decarboxylation. CH 2 CS—ACP O –OCO CH 3 C S—ACPO CH 2 CS—ACP O CH 3 C O S-Acetoacetyl—ACP

27. Dr. Wolf's CHM 424 26- 27 Fatty Acid Biosynthesis In the next step, the ketone carbonyl is reduced to a secondary alcohol. CH 2 CS—ACP O CH 3 C O S-Acetoacetyl—ACP NADPH CH 2 CS—ACP O CH 3 C OH H

28. Dr. Wolf's CHM 424 26- 28 Fatty Acid Biosynthesis The alcohol then dehydrates. CH 2 CS—ACP O CH 3 C OH H CHCS—ACP O CH 3 CH

29. Dr. Wolf's CHM 424 26- 29 Fatty Acid Biosynthesis Repeating the process gives a 6-carbon acyl group, then an 8-carbon one, then 10, etc. CH 3 CH 2 CH 2 CS—ACP O CHCS—ACP O CH 3 CH Reduction of the double bond yields ACP bearing an attached butanoyl group.

30. Dr. Wolf's CHM 424 26- 30 26.4 Phospholipids

31. Dr. Wolf's CHM 424 26- 31 PhospholipidsPhospholipids Phospholipids are intermediates in the biosynthesis of triacylglycerols. The starting materials are L -glycerol 3- phosphate and the appropriate acyl coenzyme A molecules.

32. Dr. Wolf's CHM 424 26- 32 CH 2 OPO 3 H 2 CH 2 OH H HO + R'CSCoA O RCSCoA O+ CH 2 OPO 3 H 2 CH 2 OCR H R'CO O O The diacylated species formed in this step is called a phosphatidic acid.

33. Dr. Wolf's CHM 424 26- 33 CH 2 OPO 3 H 2 CH 2 OCR H R'CO OO The phosphatidic acid then undergoes hydrolysis of its phosphate ester function. CH 2 OH CH 2 OCR H R'CO OO H2OH2OH2OH2O

34. Dr. Wolf's CHM 424 26- 34 Reaction with a third acyl coenzyme A molecule yields the triacylglycerol. CH 2 OH CH 2 OCR H R'CO OO R"CSCoAO CH 2 OCR" CH 2 OCR H R'CO O O O

35. Dr. Wolf's CHM 424 26- 35 CH 2 OPO 3 H 2 CH 2 OCR H R'CO OO Phosphatidic acids are intermediates in the formation of phosphatidylcholine. PhosphatidylcholinePhosphatidylcholine CH 2 OPO 2 CH 2 OCR H R'CO OO– (CH 3 ) 3 NCH 2 CH 2 O +

36. Dr. Wolf's CHM 424 26- 36 PhosphatidylcholinePhosphatidylcholine CH 2 OPO 2 CH 2 OCR H R'CO OO– (CH 3 ) 3 NCH 2 CH 2 O + polar "head group" hydrophobic "tail"

37. Dr. Wolf's CHM 424 26- 37 PhosphatidylcholinePhosphatidylcholine hydrophilic "head group" hydrophobic (lipophilic) "tails"

38. Dr. Wolf's CHM 424 26- 38 Cell Membranes Cell membranes are "lipid bilayers." Each layer has an assembly of phosphatidyl choline molecules as its main structural component. water water

39. Dr. Wolf's CHM 424 26- 39 Cell Membranes The interior of the cell membrane is hydrocarbon-like. Polar materials cannot pass from one side to the other of the membrane. water water

40. Dr. Wolf's CHM 424 26- 40 26.5 Waxes

41. Dr. Wolf's CHM 424 26- 41 WaxesWaxes 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. CH 3 (CH 2 ) 14 COCH 2 (CH 2 ) 28 CH 3 O Triacontyl hexadecanoate: occurs in beeswax

42. Dr. Wolf's CHM 424 26- 42 26.6 Prostaglandins

43. Dr. Wolf's CHM 424 26- 43 ProstaglandinsProstaglandins Prostaglandins are involved in many biological processes. Are biosynthesized from linoleic acid (C 18 ) via arachidonic acid (C 20 ). (See Table 26.1)

44. Dr. Wolf's CHM 424 26- 44 Examples: PGE 1 and PGF 1  O HOOOH OH HO HO OHOOH PGE 1 PGF 1 

45. Dr. Wolf's CHM 424 26- 45 Prostaglandin Biosynthesis PGE 2 is biosynthesized from arachidonic acid The oxygens come from O 2 The enzyme involved (prostaglandin endoperoxide synthase) has cyclooxygenase (COX) acitivity

46. Dr. Wolf's CHM 424 26- 46 Prostaglandin Biosynthesis Arachidonic acid O 2 fatty acid cyclooxygenase CO 2 H CH 3 PGG 2 O HOO CO 2 H CH 3 O

47. Dr. Wolf's CHM 424 26- 47 Prostaglandin Biosynthesis reduction of hydroperoxide PGG 2 O HOO CO 2 H CH 3 O PGH 2 O HO CO 2 H CH 3 O

48. Dr. Wolf's CHM 424 26- 48 Prostaglandin Biosynthesis O HO HO CO 2 H CH 3 PGE 2 PGH 2 O HO CO 2 H CH 3 O

49. Dr. Wolf's CHM 424 26- 49 IcosanoidsIcosanoids Icosanoids include: prostaglandins thromboxanes prostacyclins leukotrienes Icosanoids are compounds related to icosanoic acid CH 3 (CH 2 ) 18 CO 2 H.

50. Dr. Wolf's CHM 424 26- 50 Thromboxane A 2 (TXA 2 ) PGH 2 O HO CO 2 H CH 3 O TXA 2 O O HO CO 2 H CH 3 Thromboxane A 2 is biosynthesized from PGH 2 TXA 2 promotes platelet aggregation and blood clotting

51. Dr. Wolf's CHM 424 26- 51 Prostacyclin I 2 (PGI 2 ) PGI 2 Like thromboxane A 2, prostacyclin I 2 is biosynthesized from PGH 2 PGI 2 inhibits platelet aggregation and relaxes coronary arteries OH HO 2 C CH 3 HO O

52. Dr. Wolf's CHM 424 26- 52 Leukotriene C 4 (LTC 4 ) Leukotrienes arise from arachidonic acid via a different biosynthetic pathway. They are the substances most responsible for constricting bronchial passages during asthma attacks.

53. Dr. Wolf's CHM 424 26- 53 Leukotriene C 4 (LTC 4 ) CO 2 H OH CH 3 S CH 2 CHCNHCH 2 CO 2 H O NH CO O 2 CCHCH 2 CH 2 NH 3 + –

54. Dr. Wolf's CHM 424 26- 54 26.7 Terpenes: The Isoprene Rule

55. Dr. Wolf's CHM 424 26- 55 TerpenesTerpenes Terpenes are natural products that are structurally related to isoprene. H2CH2CH2CH2C C CH 3 CH CH 2 or Isoprene (2-methyl-1,3-butadiene)

56. Dr. Wolf's CHM 424 26- 56 TerpenesTerpenes Myrcene (isolated from oil of bayberry) is a typical terpene. CH 2 CH 3 CH 3 C CHCH 2 CH 2 CCH CH 2 or

57. Dr. Wolf's CHM 424 26- 57 The Isoprene Unit An isoprene unit is the carbon skeleton of isoprene (ignoring the double bonds) Myrcene contains two isoprene units.

58. Dr. Wolf's CHM 424 26- 58 The Isoprene Unit The isoprene units of myrcene are joined "head- to-tail." headtail tail head

59. Dr. Wolf's CHM 424 26- 59 Table 26.2 ClassNumber of carbon atoms Monoterpene10 Sesquiterpene15 Diterpene20 Sesterpene25 Triterpene30 Tetraterpene40 Classification of Terpenes

60. Dr. Wolf's CHM 424 26- 60 Figure 26.6 Representative Monoterpenes  -Phellandrene (eucalyptus) Menthol (peppermint) Citral (lemon grass) OH OH

61. Dr. Wolf's CHM 424 26- 61 Figure 26.6 Representative Monoterpenes  -Phellandrene (eucalyptus) Menthol (peppermint) Citral (lemon grass) OH OH

62. Dr. Wolf's CHM 424 26- 62 Figure 26.6 Representative Monoterpenes  -Phellandrene (eucalyptus) Menthol (peppermint) Citral (lemon grass)

63. Dr. Wolf's CHM 424 26- 63 Figure 26.6 Representative Sesquiterpenes  -Selinene (celery) H

64. Dr. Wolf's CHM 424 26- 64 Figure 26.6 Representative Sesquiterpenes  -Selinene (celery) H

65. Dr. Wolf's CHM 424 26- 65 Figure 26.6 Representative Sesquiterpenes  -Selinene (celery)

66. Dr. Wolf's CHM 424 26- 66 Figure 26.6 Representative Diterpenes Vitamin A OH

67. Dr. Wolf's CHM 424 26- 67 Figure 26.6 Representative Diterpenes Vitamin A OH

68. Dr. Wolf's CHM 424 26- 68 Figure 26.6 Representative Diterpenes Vitamin A

69. Dr. Wolf's CHM 424 26- 69 Figure 26.6 Representative Triterpene Squalene (shark liver oil) tail-to-tail linkage of isoprene units

70. Dr. Wolf's CHM 424 26- 70 26.8 Isopentenyl Pyrophosphate: The Biological Isoprene Unit

71. Dr. Wolf's CHM 424 26- 71 The Biological Isoprene Unit The isoprene units in terpenes do not come from isoprene. They come from isopentenyl pyrophosphate. Isopentenyl pyrophosphate (5 carbons) comes from acetate (2 carbons) via mevalonate (6 carbons).

72. Dr. Wolf's CHM 424 26- 72 The Biological Isoprene Unit CH 3 COH O3 HOCCH 2 CCH 2 CH 2 OH CH 3 OH O Mevalonic acid H2CH2CH2CH2C CCH 2 CH 2 OPOPOH CH 3 OO Isopentenyl pyrophosphate

73. Dr. Wolf's CHM 424 26- 73 Isopentenyl Pyrophosphate H2CH2CH2CH2C CCH 2 CH 2 OPOPOH CH 3 OO Isopentenyl pyrophosphate or OPP

74. Dr. Wolf's CHM 424 26- 74 Isopentenyl and Dimethylallyl Pyrophosphate Isopentenyl pyrophosphate is interconvertible with 2-methylallyl pyrophosphate. OPP OPP Dimethylallyl pyrophosphate has a leaving group (pyrophosphate) at an allylic carbon; it is reactive toward nucleophilic substitution at this position. Isopentenyl pyrophosphate Dimethylallyl pyrophosphate

75. Dr. Wolf's CHM 424 26- 75 26.9 Carbon-Carbon Bond Formation in Terpene Biosynthesis

76. Dr. Wolf's CHM 424 26- 76 Carbon-Carbon Bond Formation The key process involves the double bond of isopentenyl pyrophosphate acting as a nucleophile toward the allylic carbon of dimethylallyl pyrophosphate. + OPPOPP

77. Dr. Wolf's CHM 424 26- 77 Carbon-Carbon Bond Formation + OPP OPP – + OPPOPP

78. Dr. Wolf's CHM 424 26- 78 After C—C Bond Formation... + OPP The carbocation can lose a proton to give a double bond. OPP H – +

79. Dr. Wolf's CHM 424 26- 79 After C—C Bond Formation... OPP This compound is called geranyl pyrophosphate. It can undergo hydrolysis of its pyrophosphate to give geraniol (rose oil).

80. Dr. Wolf's CHM 424 26- 80 After C—C Bond Formation... OPP OH Geraniol H2OH2OH2OH2O

81. Dr. Wolf's CHM 424 26- 81 From 10 Carbons to 15 + OPPOPP Geranyl pyrophosphate + OPP

82. Dr. Wolf's CHM 424 26- 82 From 10 Carbons to 15 + OPP H –+ OPP

83. Dr. Wolf's CHM 424 26- 83 From 10 Carbons to 15 OPP This compound is called farnesyl pyrophosphate. Hydrolysis of the pyrophosphate ester gives the alcohol farnesol (Figure 26.6).

84. Dr. Wolf's CHM 424 26- 84 From 15 Carbons to 20 OPP Farnesyl pyrophosphate is extended by another isoprene unit by reaction with isopentenyl pyrophosphate. OPP

85. Dr. Wolf's CHM 424 26- 85 CyclizationCyclization Rings form by intramolecular carbon-carbon bond formation. OPP OPP + E double bond Z double bond

86. Dr. Wolf's CHM 424 26- 86+OH H –+ H2OH2OH2OH2O Limonene  -Terpineol

87. Dr. Wolf's CHM 424 26- 87 Bicyclic Terpenes ++ +  -Pinene +  -Pinene

88. Dr. Wolf's CHM 424 26- 88 26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate

89. Dr. Wolf's CHM 424 26- 89 RecallRecall CH 3 COH O3 HOCCH 2 CCH 2 CH 2 OH CH 3 OH O Mevalonic acid H2CH2CH2CH2C CCH 2 CH 2 OPOPOH CH 3 OO Isopentenyl pyrophosphate

90. Dr. Wolf's CHM 424 26- 90 Biosynthesis of Mevalonic Acid CH 3 CCH 2 CSCoA OO S-Acetoacetyl coenzyme A In a sequence analogous to the early steps of fatty acid biosynthesis, acetyl coenzyme A is converted to S-acetoacetyl coenzyme A.

91. Dr. Wolf's CHM 424 26- 91 Biosynthesis of Mevalonic Acid CH 3 CSCoA O+ CH 3 CCH 2 CSCoA OO In the next step, S-acetoacetyl coenzyme A reacts with acetyl coenzyme A. Nucleophilic addition of acetyl coenzyme A (probably via its enol) to the ketone carbonyl of S-acetoacetyl coenzyme A occurs.

92. Dr. Wolf's CHM 424 26- 92 Biosynthesis of Mevalonic Acid CH 3 CSCoA O CH 3 CCH 2 CSCoA CH 2 COH HOO O + CH 3 CCH 2 CSCoA OO

93. Dr. Wolf's CHM 424 26- 93 Biosynthesis of Mevalonic Acid CH 3 CCH 2 CSCoA CH 2 COH HOO O Next, the acyl coenzyme A function is reduced. The product of this reduction is mevalonic acid.

94. Dr. Wolf's CHM 424 26- 94 CH 3 CCH 2 CSCoA CH 2 COH HOO O CH 3 CCH 2 CH 2 OH CH 2 COH HOO Mevalonic acid

95. Dr. Wolf's CHM 424 26- 95 Conversion of Mevalonic Acid to Isopentenyl Pyrophosphate CH 3 CCH 2 CH 2 OH CH 2 COH HOHOHOHOO The two hydroxyl groups of mevalonic acid undergo phosphorylation. CH 3 CCH 2 CH 2 OPP CH 2 COH O OPO 3 2–

96. Dr. Wolf's CHM 424 26- 96 Conversion of Mevalonic Acid to Isopentenyl Pyrophosphate Phosphorylation is followed by a novel elimination involving loss of CO 2 and PO 4 3–. CH 3 CCH 2 CH 2 OPP CH 2 O OPO 3 2–C O – CH 3 CCH 2 CH 2 OPP CH 2 OPO 3 3–OCO

97. Dr. Wolf's CHM 424 26- 97 Conversion of Mevalonic Acid to Isopentenyl Pyrophosphate The product of this elimination is isopentenyl pyrophosphate. CH 3 CCH 2 CH 2 OPP CH 2

98. Dr. Wolf's CHM 424 26- 98 Biosynthetic pathway is based on experiments with 14 C-labeled acetate CH 3 COH O HOCCH 2 CCH 2 CH 2 OH CH3CH3CH3CH3OH O Mevalonic acid H2CH2CH2CH2C CCH 2 CH 2 OPOPOH CH3CH3CH3CH3OO Isopentenyl pyrophosphate

99. Dr. Wolf's CHM 424 26- 99 Biosynthetic pathway is based on experiments with 14 C-labeled acetate CH 3 COH O Citronellal biosynthesized using 14 C-labeled acetate as the carbon source had the labeled carbons in the positions indicated. H2CH2CH2CH2C CCH 2 CH 2 OPOPOH CH3CH3CH3CH3OO O H

100. Dr. Wolf's CHM 424 26- 100 26.11 Steroids: Cholesterol

101. Dr. Wolf's CHM 424 26- 101 Structure of Cholesterol Fundamental framework of steroids is the tetracyclic unit shown.

102. Dr. Wolf's CHM 424 26- 102 Structure of Cholesterol Cholesterol has the fundamental steroid skeleton modified as shown. HO CH 3 H H H

103. Dr. Wolf's CHM 424 26- 103 Structure of Cholesterol Some parts of the cholesterol molecule are isoprenoid. But other parts don't obey the isoprene rule. Also, cholesterol has 27 carbons, which is not a multiple of 5. HO CH 3 H H H

104. Dr. Wolf's CHM 424 26- 104 Biosynthesis of Cholesterol Cholesterol is biosynthesized from the triterpene squalene. In the first step, squalene is converted to its 2,3-epoxide. O O 2, NADH, enzyme

105. Dr. Wolf's CHM 424 26- 105 Biosynthesis of Cholesterol To understand the second step, we need to look at squalene oxide in a different conformation, one that is in a geometry suitable for cyclization. O O

106. Dr. Wolf's CHM 424 26- 106 Biosynthesis of Cholesterol Cyclization is triggered by epoxide ring opening. O H+H+H+H+ + HO H

107. Dr. Wolf's CHM 424 26- 107 Biosynthesis of Cholesterol The five-membered ring expands to a six-membered one. + HO H H HOH

108. Dr. Wolf's CHM 424 26- 108 Biosynthesis of Cholesterol Cyclization to form a tetracyclic carbocation. H HOH HHHO protosteryl cation

109. Dr. Wolf's CHM 424 26- 109 Biosynthesis of Cholesterol Deprotonation and multiple migrations. HO OH 2 H H HO H H

110. Dr. Wolf's CHM 424 26- 110 Biosynthesis of Cholesterol The product of this rearrangement is a triterpene called lanosterol. A number of enzyme-catalyzed steps follow that convert lanosterol to cholesterol. HO H H

111. Dr. Wolf's CHM 424 26- 111 CholesterolCholesterol Cholesterol is the biosynthetic precursor to a large number of important steroids: Bile acids Vitamin D Corticosteroids Sex hormones

112. Dr. Wolf's CHM 424 26- 112 26.12 Vitamin D

113. Dr. Wolf's CHM 424 26- 113 CholesterolCholesterol HO CH 3 H H H Cholesterol is the precursor to vitamin D. Enzymes dehydrogenate cholesterol to introduce a second double bond in conjugation with the existing one. The product of this reaction is called 7-dehydrocholesterol.

114. Dr. Wolf's CHM 424 26- 114 7-Dehydrocholesterol7-Dehydrocholesterol HO CH 3 H H Sunlight converts 7-dehydrocholesterol on the skin's surface to vitamin D 3.

115. Dr. Wolf's CHM 424 26- 115 Vitamin D 3 CH 3 HO H Insufficient sunlight can lead to a deficiency of vitamin D 3, interfering with Ca 2+ transport and bone development. Rickets can result.

116. Dr. Wolf's CHM 424 26- 116 26.13 Bile Acids

117. Dr. Wolf's CHM 424 26- 117 CholesterolCholesterol HO CH 3 H H H Oxidation in the liver degrades the cholesterol side chain and introduces OH groups at various positions on the steroid skeleton. Cholic acid (next slide) is the most abundant of the bile acids.

118. Dr. Wolf's CHM 424 26- 118 Cholic Acid Salts of cholic acid amides (bile salts), such as sodium taurocholate (next slide), act as emulsifying agents to aid digestion. HOHOHOHO CH 3 H H H H OHOHOHOH HOHOHOHOOOH

119. Dr. Wolf's CHM 424 26- 119 Sodium Taurocholate HOHOHOHO CH 3 H H H H OHOHOHOH HOHOHOHOO NHCH 2 CH 2 SO 3 Na

120. Dr. Wolf's CHM 424 26- 120 26.14 Corticosteroids

121. Dr. Wolf's CHM 424 26- 121 CholesterolCholesterol HO CH 3 H H H Enzymatic degradation of the side chain and oxidation of various positions on the steroid skeleton convert cholesterol to corticosteroids.

122. Dr. Wolf's CHM 424 26- 122 CortisolCortisol Cortisol is the most abundant of the corticosteroids. Enzyme-catalyzed oxidation of cortisol gives cortisone. O CH 3 H H H OHOHOHOH HOHOHOHO O OHOHOHOH

123. Dr. Wolf's CHM 424 26- 123 CortisoneCortisone Corticosteroids are involved in maintaining electrolyte levels, in the metabolism of carbohydrates, and in mediating the allergic response. O CH 3 H H H OHOHOHOH O O OHOHOHOH

124. Dr. Wolf's CHM 424 26- 124 26.15 Sex Hormones

125. Dr. Wolf's CHM 424 26- 125 TestosteroneTestosterone Testosterone is the main male sex hormone. O H H H H3CH3CH3CH3C H3CH3CH3CH3COH

126. Dr. Wolf's CHM 424 26- 126 EstradiolEstradiol Estradiol is a female sex hormone involved in regulating the menstrual cycle and in reproduction. HO H H H H3CH3CH3CH3C OH

127. Dr. Wolf's CHM 424 26- 127 ProgesteroneProgesterone Supresses ovulation during pregnancy. O H H H H3CH3CH3CH3C H3CH3CH3CH3CO

128. Dr. Wolf's CHM 424 26- 128 26.16 Carotenoids

129. Dr. Wolf's CHM 424 26- 129 CarotenoidsCarotenoids Carotenoids are naturally occurring pigments. Structurally, carotenoids are tetraterpenes. They have 40 carbons. Two C 20 units are linked in a tail-to-tail fashion. Examples are lycopene and  -carotene.

130. Dr. Wolf's CHM 424 26- 130 CarotenoidsCarotenoids Lycopene (tomatoes)  -Carotene (carrots)

131. Dr. Wolf's CHM 424 26- 131 End of Chapter 26