1. Chapter 24
Lipids

2. Lipids
Lipids: a class of naturally occurring organic compounds which are:
insoluble in water, but soluble in organic solvents
Lipids are generally put into three classes
Storage Lipids
Structural Lipids
Lipids as Signals, Cofactors, and Pigments

3. Lipids Storage Lipids (80% of the mass of a fat cell) Fatty acids
Long chain alkane or alkene with carboxylic acid at one end.
Triacylglycerols
Glycerol triester of three fatty acids
Waxes
Fatty acid ester with long chain alcohol

4. Lipids Structural Lipids (5% to 10% of dry mass of most cells)
Phosphoacylglycerols (glycerophospholipids)
Galactolipids (glycolipids)
Sulfolipids
Sphingolipids
Cholesterol (and Bile acids)

5. Lipids Signals, Cofactors, and Pigments Steroid hormones
Lipid-soluble vitamins
Eicosanoids (not transported in the blood)
Prostaglandins
Thromboxanes
Leukotrienes

6. Triglyceride
Triglyceride: an ester of glycerol with three fatty acids

7. Fatty Acids
Fatty acid: an unbranched-chain carboxylic acid derived from hydrolysis of animal fats, vegetable oils, or membrane phospholipids
nearly all have an even number of carbon atoms, most between 12 and 20, in an unbranched chain
the three most abundant are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1)
in most unsaturated fatty acids, the cis isomer predominates; the trans isomer is rare
unsaturated fatty acids have lower melting points than their saturated counterparts; the greater the degree of unsaturation, the lower the melting point

8. Fatty Acids

9. Triglycerides Physical properties depend on the fatty acid components
melting point increases as the number of carbons in the hydrocarbon chains increases and as the number of double bonds decreases
triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oils
triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fats

10. Triglycerides
The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape
hydrocarbon chains of saturated fatty acids can lie parallel with strong London dispersion forces between their chains; they pack into well-ordered, compact crystalline forms and melt above room temperature
because of the cis configuration of the double bonds in unsaturated fatty acids, their hydrocarbon chains have a less ordered structure and London dispersion forces between them are weaker; these triglycerides have melting points below room temperature

11. Hydrogenation
Hardening: reduction of some or all of the carbon-carbon double bonds of an unsaturated triglyceride using H2/catalyst
in practice, the degree of hardening is carefully controlled to produce fats of a desired consistency
the resulting fats are sold for kitchen use (Crisco, Spry, Dexo, and others)
margarine and other butter substitutes are produced by partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils

12. Soaps
Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap)

13. Soaps Soaps clean by acting as emulsifying agents
their long hydrophobic hydrocarbon chains cluster so as to minimize their contact with water
their polar hydrophilic carboxylate groups remain in contact with the surrounding water molecules
driven by these two forces, soap molecules spontaneously cluster into micelles

14. Soaps
soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard water)

15. Complex Lipids Phospholipids Glycolipids
contain an alcohol, two fatty acids, and a phosphate ester
in glycerophospholipids, the alcohol is glycerol
in sphingolipids, the alcohol is sphingosine
Glycolipids
complex lipids that contain a carbohydrate

16. Complex Lipids
Sphingosine – amino alcohol
Glycerol

17. Membranes
Complex lipids form the membranes around cells and small structures within cells
In aqueous solution, complex lipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers
polar head groups are in contact with the aqueous environment
nonpolar tails are buried within the bilayer
the major force driving the formation of lipid bilayers is hydrophobic interaction
the arrangement of hydrocarbon tails in the interior can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids)

18. Fluid Mosaic Model

19. Glycerophospholipids
Glycerophospholipids are the second most abundant group of naturally occurring lipids
they are also called phosphoglycerides
found almost exclusively in plant and animal membranes, which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins
the most abundant phosphoacylglycerols are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid
the three most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1)

20. Glycerophospholipids
A phosphatidic acid
the fatty acid on carbon 2 is always unsaturated
further esterification with a low-molecular-weight alcohol gives a glycerophospholipid

21. Glycerophospholipids
More often phosphatidyl____________

22. Glycerophospholipids
a lecithin (phosphotidylcholine)

23. Sphingolipids Found in the coatings of nerve axons (myelin)
contain the long-chain aminoalcohol, sphingosine,

24. Glycolipids Glycolipid: a complex lipid that contains a carbohydrate
the carbohydrate is either glucose or galactose
the cerebrosides are ceramide mono- or oligosaccharides

25. Steroids
Steroids: a group of plant and animal lipids that have this tetracyclic ring structure

26. Cholesterol Cholesterol is the most abundant steroid in the human body
in plasma membranes in all animal cells
precursor of all steroid hormones and bile acids

27. Lipoproteins
Cholesterol, along with fats, are transported by lipoproteins

28. Lipoproteins
Schematic of a low-density lipoprotein

29. Cholesterol Transport
transport of cholesterol from the liver starts with VLDL
VLDL is carried in the serum
as fat is removed, its density increases and it becomes LDL; LDL stays in the plasma for about 2.5 days
LDL carries cholesterol to cells, where specific LDL receptors bind it
after binding, LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters

30. Cholesterol Transport
high-density lipoproteins (HDL) transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL
while in the serum, free cholesterol in HDL is converted to cholesteryl esters
in the liver, HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell
these esters are used for the synthesis of steroid hormones and bile acids
after LDL has delivered its cholesteryl esters to liver cells, it reenters circulation

31. Levels of LDL and HDL most of the cholesterol is carried by LDL
normal plasma levels are 175 mg/100 mL
if there are sufficient LDL receptors on the surface of cells, LDL is removed from circulation and its concentration drops
the number of LDL receptors is controlled by a feedback mechanism
when the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed
in the disease called hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may be as high as 680 mg/100 mL

32. Levels of LDL and HDL
these high levels of cholesterol can cause premature atherosclerosis and heart attacks
in general, high LDL means high cholesterol content in the plasma because LDL cannot get into cells
therefore, high LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis
the serum cholesterol level controls cholesterol synthesis in the liver
when serum cholesterol is high, its synthesis in the liver is low, and vice versa
the commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase

33. Steroid Hormones Androgens: male sex hormones
synthesized in the testes
responsible for the development of male secondary sex characteristics

34. Steroid Hormones
Among the synthetic anabolic steroids are

35. Steroid Hormones Estrogens: female sex hormones
synthesized in the ovaries
responsible for the development of female secondary sex characteristics and control of the menstrual cycle

36. Steroid Hormones
Progesterone-like analogs are used in oral contraceptives

37. Steroid Hormones Glucorticoid hormones
synthesized in the adrenal cortex
regulate metabolism of carbohydrates
decrease inflammation
involved in the reaction to stress

38. Bile Salts Bile salts, the oxidation products of cholesterol
synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats

39. Prostaglandins
Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid

40. Prostaglandins
Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers
one such polyunsaturated fatty acid is arachidonic acid

41. Prostaglandins

42. COX Enzymes The COX enzyme occurs in two forms
COX-1 catalyzes the normal physiological production of prostaglandins
COX-2 is responsible for the production of prostaglandins in inflammation
when a tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with resident cells, for example, smooth muscle cells
this interaction activates COX-2 and prostaglandins are synthesized

43. Thromboxanes Thromboxanes are also derived from arachidonic acid
thromboxane A2 induces platelet aggregation and vasoconstriction
aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme

44. Leukotrienes Leukotrienes are also synthesized from arachidonic acid
they occur mainly in leukocytes
they produce muscle contractions, especially in the lungs … can cause asthma-like attacks
they are 100 times more potent than histamine
anti-asthma drugs inhibit leukotrienes synthesis

45. Lipids
End
Chapter 20