1、Chapter 10 Lipids1. Lipids encompass a large and diverse group of organic compounds1.1 Lipids are broadly defined as biological molecules that are soluble in organic solvents.1.1.1 Lipids are usually extracted from biological materials by nonpolar solvents like ether, chloroform（氯仿）（氯仿）, benzene（苯）（

2、苯）.1.2 The biological functions of lipids are diverse.1.2.1 Certain lipids (e.g., triacylglycerols（三脂酰甘油）（三脂酰甘油）, commonly called fats) serve as efficient reserves for the storage of energy. 1.2.2 Lipids (including mainly glycerophospholipids （甘油磷脂）（甘油磷脂）, sphingolipids, and sterols) are the major s

3、tructural elements of the biomembranes. 1.2.3 The water-insoluble vitamins like vitamin A, D, E, K and some hormones (like steroids（類固醇）（類固醇）, prostaglandins（前列腺素）（前列腺素）) are lipids.1.2.4 The bile acids help to solubilize (emulsify) other classes of lipids for better digestion.1.2.5 Lipids also serv

4、e as enzyme cofactors, light-absorbing pigments, intracellular messengers.Fat cells of guinea pigA cotyledon cell from a seed of the plant arabidopsisFatty acid composition of three food fatsMelting pointas affected by the proportion of saturated fatBeewax: an ester of palmitic acid（軟脂酸）（軟脂酸） with t

5、he alcohol triacontanol2. Fatty acids are a class of compounds containing a long hydrocarbon chain and a terminal carboxylate group2.1 Fatty acids can be saturated or unsaturated.2.1.1 Saturated fatty acids do not contain carbon-carbon double bonds.2.1.2 The two most common saturated fatty acids are

6、 palmitic and stearic acids（軟脂酸和硬（軟脂酸和硬脂酸）脂酸）, containing 16 and 18 carbons, respectively (abbreviated as 16:0 and 18:0).2.1.3 Unsaturated fatty acids contain one or more carbon-carbon double bonds, usually of cis configuration in the aliphatic（脂肪族的）（脂肪族的） chains.2.1.4 Positions of double bonds are

7、specified by superscript numbers following a symbol, e.g., linoleic acid（亞油酸）（亞油酸） is abbreviated as 18:2( 9,12).2.1.5 The number of carbons in a fatty acid is commonly even and the positions of carbon-carbon double bonds are regular (usually at positions 9, 12, 15 (+3), separated by a methylene gro

8、up and never conjugate, that is, alternating single and double bonds). (cis).2.1.6 Oleic acid（油酸）（油酸）, 18:1( 9), is the most common monounsaturated fatty acid in mammals.2.1.7 Linoleic acid, 18:2( 9,12), and linolenic acid（亞麻酸）（亞麻酸）, 18:3( 9,12,15), can not be synthesized by mammals and are called e

9、ssential fatty acids (like vitamins, they have to be taken from food).2.2 The physical properties of fatty acids are mainly determined by the length and degree of unsaturation on the hydrocarbon chain.2.2.1 The shorter the hydrocarbon chain, the lower its melting point (saturated fatty acids of 10 o

10、r less carbon atoms are liquid, of 12 or more carbons are waxy or solid at room temperature).2.2.2 Existence of carbon-carbon double bonds lowers the melting point of fatty acids due to the kink introduced by double bonds (therefore preventing the tight packing).2.3 Fatty acids are usually found as

11、components of complex lipids.2.3.1 Fatty acids are major components of the triacylglycerols, the common storage lipids.2.3.2 Fatty acids are also components of the membrane phospolipids and glycolipids.2.3.3 A small amount of free fatty acids are carried by serum albumin（血清白蛋白）（血清白蛋白） in the blood o

12、f vertebrate animals.2.4 Triacylglycerols are fatty acid esters of glycerol（甘油）（甘油） and provide stored energy and insulation.2.4.1 Triacylglycerols are nonpolar, hydrophobic, and essentially insoluble in water.2.4.2 Triacylglycerols serve as stored energy in animal adipocytes (fat cells) and plant s

13、eeds.2.4.3 Oxidation of triacylglycerols yields more than twice the amount of energy than carbonhydrates or proteins, gram for gram (due to the higher level of reduction of the acyl（酰基）（酰基） groups).2.4.4 Triacylglycerols（三脂酰甘油）（三脂酰甘油） are unhydrated and thus much lighter than saccharides, which are

14、highly hydrated (e.g., one gram of dry glycogen binds two grams of water!).2.4.5 Warm-blooded polar animals are amply padded with triacylglycerols as insulation against very low temperatures.Oleic acid or OileateStearic acid3. Glycerophospholipids（甘油磷脂）（甘油磷脂）, sphingolipids（鞘脂）（鞘脂）, and sterols（膽固醇）

15、（膽固醇） are the three major types of lipids present in biomembranes.3.1 Glycerophospholipids are derivatives of phosphatidic acid （磷脂酸）（磷脂酸）(i.e., 1,2-diacylglycerol-3-phosphate)3.1.1 Different polar alcohols are joined to the phosphate（磷酸鹽）（磷酸鹽） group to make the various glycerophospholipids. 3.1.2 G

16、lycerophospholipids are usually named for their head alcohol groups with the prefix “phosphatidyl”: e.g., phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidyl glycerol, phosphatidylinositol. 3.1.3 In cardiolipin（二磷脂酰甘油）（二磷脂酰甘油）, two phosphatidic acids share a single glycer

17、ol (fig.).3.1.4 In plasmalogens（縮醛磷脂）（縮醛磷脂） and platelet-activating factor（PAF，血小板活化因，血小板活化因子）子）, one hydrocarbon chain form a ether linkage to the glycerol backbone.3.1.5 In general, a glycerophospholipid （甘油磷脂）（甘油磷脂） contains a saturated fatty acid at C-1, and an unsaturated fatty acid at C-2 (com

18、monly 16 or 18 carbon long).3.2 Sphingolipids are derivatives of sphingosine（(神經神經) 鞘氨醇）鞘氨醇）.3.2.1 Sphingosine is a long-chain amino alcohol (with amino group at C-2, hydroxyl groups at C-1 and C-3) having a carbon-carbon double bond between C-4 and C-5.3.2.2 The two -OH groups at C-1, C-3, and the

19、-NH2 amino group at C-2 are structurally homologous with the three -OH groups of glycerol in glycerophospholipids（甘油磷脂）（甘油磷脂）.3.2.3 The fundamental structural unit common to all sphingolipids（神經鞘脂）（神經鞘脂） is ceramide（神經酰胺）（神經酰胺） having a fatty acid attached to the 2-NH2 group in amide linkage.3.2.4 S

20、phingolipids can be categorized as three subclasses, differing in their polar head groups: sphingomyelins（(神經神經)鞘磷脂）鞘磷脂） (containing phosphoholine or phosphoethanolamine), neutral glycolipids (containing one or a few neutral sugars like glucose, galactose), gangliosides (containing complex oligosacc

21、harides with at least one negatively charged N-acetylneuraminic acid or sialic acid).3.2.5 The glycolipids having only one sugar residue (either galactose or glucose) at the head are called cerebroside （腦苷脂）（腦苷脂）(being the simplest glycolipids). (function?)3.2.6 Both glycerophospholipids and sphingo

22、myelins are phospholipids with similar molecular structures. (overlap in classification).3.2.7 Sphingolipids are involved in biological recognition: e.g., glycosphingolipids (of various sugar groups at the end of the head oligosaccharides) are part of the determinants of the human blood groups A, B,

23、 and O. (cell surface antigens?).3.3 Sterols contain a characteristic steroid nucleus of four fused hydrocarbon rings.3.3.1 Three of the fused rings are six-membered, one is five-membered.3.3.2 The fusion of the rings make the C-C bonds not rotatable, which in turn makes the steroid nucleus almost p

24、lanar and rigid.3.3.3 Cholesterol（膽固醇）（膽固醇） is the major sterol in membranes of animal cells.3.3.4 The carbon atoms of the cholesterol are numbered.3.3.5 The hydroxyl group at C-3 is the polar head and the rest nonpolar part.3.3.6 Sterols similar to cholesterol are found in plants and fungi.3.3.7 Ba

25、cteria often lack sterols.3.3.8 Sterols serve as precursors for a variety of products including bile acids (with a polar side chain at C-17, acting as emulsifying agents in animal intestines) and many steroid hormones (fig.).3.3.9 Many Nobel Prizes have been awarded to works related to cholesterol.3

26、.4 Specific enzymes degrade membrane lipids.3.4.1 Phospholipases（磷脂酶）（磷脂酶） A1 and A2 hydrolyze the ester bonds of intact glycerophospholipids at C-1 and C-2 of glycerol, respectively.3.4.2 Phospholipases C and D each hydrolyze one of the two phosphodiester bonds in the head group. (fig of the bonds

27、broken).3.4.3 Some inherited human diseases are results of abnormal accumulations of membrane lipids (e.g., Niemann-Pick disease, the Tay-Sachs disease).5. Some lipids have specific biological activities.5.1 Cholesterol is the precursor of five major classes of steroid hormones5.1.1 Progestagens (su

28、ch as progesterone) prepare the uterus for implantation of an egg and prevent ovulation during pregnancy.5.1.2 Androgens, or male sex hormones (such as testosterone) are responsible for the development of male secondary sex characteristics.5.1.3 Estrogen, or female sex hormones (such as estradiol) a

29、re reponsible for the development of female secondary sex characteristics.5.1.4 Glucocorticoids（糖（糖(腎上腺腎上腺)皮質激素）皮質激素） (such as cortisol) promotes gluconeogenesis.5.1.5 Mineralocorticoids（鹽皮質激素）（鹽皮質激素） (such as aldosterone) act on the renal tubules to increase the reabsorption of Na+ and the excretio

30、n of K+ and H+, leading to an increase in blood volume and blood pressure.5.1.6 These steroid hormones are synthesized from cholesterol mainly in the gonads and adrenal cortex and carried in the bloodstream to target tissues.5.1.7 The steroid hormones bind to highly specific receptors and move into

31、cell nucleus to regulate gene transcription.5.2 Receptor-triggered hydrolysis of phosphatidylinositol bisphosphate on plasma membranes generates two secondary messengers.5.2.1 Binding of certain hormones (e.g., vasopressin) to specific receptors on cell surfaces leads to activation of the membrane b

32、ound phospholipase C.5.2.2 Phospholipase C catalyzes the hydrolysis of phosphatidyl inositol 4,5-bisphophate (PIP2) to form inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG).5.2.3 IP3 further triggers release of intracellular Ca2+, which leads to activation of many Ca2+-dependent enzymes.5.

33、2.4 DAG activates protein kinase C, which further activates many enzymes by phosphorylation.5.3 Eicosanoids are derivatives of arachidonic acid, 20:4(5,8,11,14), and have a variety of extremely potent hormone-like actions on vertebrate tissues.5.3.1 Arachidonic acid is released from membrane phospho

34、lipids by the catalysis of phospholipase A2 in response to certain hormone signals.5.3.2 Three major classes of eicosanoids have been identified. 5.3.3 Prostaglandins （前列腺素）（前列腺素）(PG) contain a characteristic five-carbon ring. (fig.).5.3.4 Prostaglandins seem to have multiple functions including sti

35、mulation of contraction of smooth muscles, raising body temperature (producing fever), causing inflammation, regulating blood flow to particular organs, generating wake-sleep cycle, resulting in pain. 5.3.5 Thromboxanes（血栓素，凝血噁烷）（血栓素，凝血噁烷） (TX) contain a characteristic six-membered ether ring.5.3.6

36、Thromoboxanes are synthesized by platelets and act in blood clotting.5.3.7 Leukotrienes（白三烯（白三烯,白細胞三烯，白白細胞三烯，白細胞血管收縮素）細胞血管收縮素） contain three characteristic conjugated double bonds.5.3.8 Overproduction of leukatrienes causes asthmatic and anaphylactic shocks.5.3.9 Sue Bergstrom, Bengt Ingemar Samuels

37、son, and John Robert Vane won the 1982 Nobel Prize in medicine or physiology for studying prostaglandins and related bioactive compounds.5.4 Vitamins A, D, E, K are all isoprenoid（類異（類異戊二烯戊二烯(的的)） compounds synthesized by the condensation of isoprene units (also precursors of sterols).5.4.1 Vitamin

38、A (retinol) is usually derived from b b-carotenoids, light-absorbing pigments existing in many yellow-colored plants (like carrots, sweet potatoes).5.4.2 Vitamin A (11-trans-retinol) is the precursor of 11-cis-retinal, an essential pigment for vision (the cofactor of rhodopsin（視紫質（視紫質, 視視網膜紫質）網膜紫質）)

39、. 5.4.3 Vitamin D is derived from 7-dehydrocholesterol（脫氫膽甾醇）（脫氫膽甾醇）in the skin by irradiation.5.4.4 Vitamin D is the precursor of 1,25-dihydroxycholecalciferol, a hormone regulating the uptake of calcium and phosphate (in what forms from where, kidney, intestine, bone). 5.4.5 Vitamin D deficiency i

40、n children produces rickets (resulting from inadequate calcification of cartilage and bone).5.4.6 Vitamin E (also called tocopherols) contain a substituted aromatic ring and a long hydrocarbon side chain.5.4.7 Vitamin E was first recognized as an compound that prevented sterility in rats.5.4.8 The f

41、unction of vitamin E is still not clear, but is believed to act as an antioxidant to prevent peroxidation of polyunsaturated fatty acids. 5.4.9 Vitamin K is a quinone（醌，苯醌）（醌，苯醌） needed for blood clotting. 5.4.10 Vitamin K acts as a cofactor in converting Glu residues into g g-carboxylglutamate in p

42、rothrombin（凝血素）（凝血素）, modifications making prothrombin a much stronger Ca2+ chelator（螯合劑）（螯合劑）.5.4.11 Binding of Ca2+ helps the proteolytic（ (分分)解蛋白的解蛋白的,蛋白水解的）蛋白水解的） activation of prothrombin into thrombin（凝血酶）（凝血酶）, which converts fibrinogen（纖維蛋白原）（纖維蛋白原） into fibrin（ (血血)纖維蛋白纖維蛋白, (血血)纖維）纖維） whic

43、h forms blood blots.5.4.12 George Wald share the 1967 Nobel Prize in medicine or physiology for his studies on vitamin A.5.4.13 Adolf Otto Reinhold Windaus won the 1928 Nobel Prize in Chemistry for discovering the cholesterol derived from vitamin D3.5.4.14 Henrik Dam and Edward A. Doisy won the 1943

44、 Nobel Prize in medicine or physiology for their studies on vitamin K.Vitamin DSkin to liverto kidney4. Membrane lipids are amphipathic（兩性分子（兩性分子的的 ） and form ordered structures spontaneously in water4.1 All membrane lipids contain a polar (hydrophilic) head and a nonpolar (hydrophobic) tail.4.1.1 Membrane lipids are usually represented by a circle head and one or two attached wavy or straight lines as the tails.4.2 The amphipathic membrane lipids form ordered