第 2 章脂类 Lipids

第2章脂类 Lipids

1.脂结构、功能的多样性 1.1脂常被定义为不溶于水的（或微溶的）有机化合物 1.1.1 脂可溶于氯仿,苯. 1.2 脂的生物学功能是多样的. 1.2.1 某些脂类 (e.g., triacylglycerols（三脂酰甘油）) 常作为能量的储存单位

1.2.2脂（包括甘油磷脂、鞘磷脂和固醇）是所有生物膜的重要结构成分1.2.2脂（包括甘油磷脂、鞘磷脂和固醇）是所有生物膜的重要结构成分 1.2.3 不能溶于水的维生素 A, D, E, K 和一些前列腺素 (象类固醇、前列腺素) 都是脂. 1.2.4 生长因子. 1.2.5 脂常作为光吸收色素，细胞内的信号分子 1.2.6 抗氧化剂

2.脂肪酸包含一个长的碳氢链和一个羧酸基团（末端） p82 2.1 脂肪酸分为饱和脂肪酸和不饱和脂肪酸 2.1.1 饱和脂肪酸没有C—C双键 2.1.2 最普遍的饱和脂肪酸是软脂酸和硬脂酸；16:0 and 18:0. 2.1.3 不饱和脂肪酸有一个或一个以上的C—C双键，且常为顺式结构.

Carbon #1 Two representation of the fully saturated acid, stearic acid(硬脂酸)—18:0 The zigzag form and space-filling model Carbon #18

2.1.4 命名：例如，亚油酸 18:2(9,12). 2.1.5 脂肪酸双键的位置基本上在 9, 12, 15 (+3)上，且常为顺式结构.

2.1.6 （油酸）, 18:1(9), 是哺乳动物中最常见的不饱和酸。 2.1.7 亚油酸, 18:2(9,12), 和亚麻酸, 18:3(9,12,15), 在哺乳动物中不能被合成，因此称为必需脂肪酸(象维生素一样,它们必须从食物中获得).

Unsaturated bond (a cis double bond- rigid bend) Oleic Acid (18:1D9) 油酸

2.2脂肪酸的物理性质主要由碳氢链的长度和不饱和度决定的。2.2脂肪酸的物理性质主要由碳氢链的长度和不饱和度决定的。 2.2.1随着烃链长度的增加，饱和脂肪酸的熔点也随之增高(在室温下，10碳以下的饱和脂肪酸常为液态, 12个碳以上的饱和脂肪酸常为固态). 2.2.2 cis不饱和脂肪酸的熔点比同等链长的饱和脂肪酸的熔点低

hydrophobic Fully saturated fatty acids in the extended form pack into nearly crystalline arrays, stabilized by many hydrophobic interactions

hydrophobic The presence of one or more cis double bonds interferes with this tight packing and results in less stable aggregates. Less stable aggregates

Structural Basis of Melting points for fatty acids

2.3 脂肪酸可以作为代谢中的重要的燃料分子，脂肪酸氧化获得的能量（～37kj/g-1）比蛋白质或糖氧化产生的能量（～16kj/g-1）高得多。脂肪酸通常都是以中性脂三脂酰甘油（triacylglycerols）形式贮存的。

2.4三脂酰甘油 2.4.1三脂酰甘油不溶于水 2.4.2三脂酰甘油主要位于动物的脂肪细胞内和植物的种子中 2.4.3三脂酰甘油氧化能产生大量的能量，比糖产生的能量要高得多.

2.4.4 三脂酰甘油比糖结合的水要少 (e.g., 一克肝糖原能结合2克水!). 2.4.5 位于两极的温血动物有大量的三脂酰甘油，具有保温的作用.

(a) Cross section of four guinea pig adipocytes, showing huge fat droplets that virtually fill the cells. Also visible are several capillaries in cross section. Fat droplets

(b) Cross section of a cotyledon cell from a seed of the plant Arabidopsis. The large dark structures are protein bodies, which are surrounded by stored oils in the light-colored oil bodies.

Sperm Whales Major component: lipid Controls density and buoyancy when diving deep into the ocean

Fatty acid composition of three food fats. Olive oil, butter, and beef fat consist of mixtures of triacylglycerols, differing in their fatty acid composition. The melting points of these fats—and hence their physical state at room temperature (25℃)—are a direct function of their fatty acid composition. Olive oil has a high proportion of long-chain (C16 and C18) unsaturated fatty acids, which accounts for its liquid state at 25 ℃. The higher proportion of long-chain (C16 and C18) saturated fatty acids in butter increases its melting point, so butter is a soft solid at room temperature. Beef fat, with an even higher proportion of long-chain saturated fatty acids, is a hard solid.

Wax—bee was from honeycomb (a) Triacontanoylpalmitate, the major component of beeswax, is an ester of palmitic acid（棕榈酸） with the alcohol triacontanol.

(b) A honeycomb, constructed of beeswax, is firm at 25℃ and completely impervious to water. The term “wax” originates in the Old English weax, meaning “the material of the honeycomb.”

3. 甘油磷脂, 鞘脂, 胆固醇是生物膜从最常见的两性脂. 3.1最简单的甘油磷脂是磷脂酸（phosphatidate），它是由两个在甘油-3-磷酸的C-1和C-2处成酯的脂酰基组成的 3.1.1在更复杂的甘油磷脂中，磷酸与甘油以及另一个带有一个-OH的化合物都发生酯化反应

3.1.2磷脂酰乙醇胺（phosphatidylethanolamine）、磷脂酰胆碱（phosphatidylcholine）和磷脂酰丝氨酸（phosphatidylserine）3种甘油磷脂是生物膜脂的最主要成员。3.1.3 二磷脂酰甘油 3.1.4缩醛磷脂（plasmalogen ）有一个烃链是通过一个乙烯醚键与甘油骨架的C-1连接的。血小板激活因子（platelet activating factor，PAF）分子中的甘油骨架C-1处连有烷醚基，而C-2处连有乙酰基

Unusual phospholipids: Plasmalogens: ether-linked alkenyl chain instead of ester-linked fatty acid

PAF: long ether-linked alkyl chain at C-1, C-2 is linked to Acetic acid—more solubility Released by basophils to stimulate platelet aggregation and release of serotonin (vasoconstrictor)

3.1.5 通常，甘油磷脂在 C-1 的位置有一个饱和脂肪酸。在C-2的位置有一个不饱和的脂肪酸 (一般有 16 或 18个碳). 3.2鞘脂 3.2.1神经酰胺有一个长的氨基酸链（ C-2有氨基酸链， C-1 和C-3位置有羟基），并且在C-4 和 C-5之间有一个双键

3.2.2所有鞘脂代谢的前体－神经酰胺（ceramide）是由一个通过酰胺键与鞘氨醇的C-2氨基连接的脂肪酸构成的，鞘脂家族中的三个主要成员是鞘磷脂（sphingomyelins）、脑苷脂（cerebrosides）和神经节苷脂（gangliosides）。3.2.2所有鞘脂代谢的前体－神经酰胺（ceramide）是由一个通过酰胺键与鞘氨醇的C-2氨基连接的脂肪酸构成的，鞘脂家族中的三个主要成员是鞘磷脂（sphingomyelins）、脑苷脂（cerebrosides）和神经节苷脂（gangliosides）。

(like diacylglycerol) Sphingolipids: Derived from sphingosine—a amino alcohol N-acetylneuraminic acid (sialic acid)

sphingosine glycerol Palmitic acid The similarities in shape and in molecular structure of phosphatidylcholine (a glycerophospholipid) and sphingomyelin (a sphingolipid) are clear when their space-filling and structural formulas are drawn as here.

N-acetylneuraminic acid (sialic acid)

3.2.3鞘磷脂是由连接在神经酰胺C-1羟基上的磷酰胆碱组成的。鞘磷脂存在于大多数哺乳动物细胞的质膜内，是包围着某些神经细胞的髓鞘的主要成分。 3.2.3鞘磷脂是由连接在神经酰胺C-1羟基上的磷酰胆碱组成的。鞘磷脂存在于大多数哺乳动物细胞的质膜内，是包围着某些神经细胞的髓鞘的主要成分。

3.2.4脑苷脂是含有一个单糖残基的糖鞘脂，是一个极性头部为ß-D-半乳糖残基的脑苷脂3.2.4脑苷脂是含有一个单糖残基的糖鞘脂，是一个极性头部为ß-D-半乳糖残基的脑苷脂 3.2.5神经节苷脂是最复杂的糖鞘脂，分子中含有的N-乙酰神经氨酸的寡糖链连接在神经酰胺上 3.2.6鞘脂类物质在生物识别中起到了非常重要的作用

Glycosphingolipids as determinants of blood groups. The human blood groups (O, A, B) are determined in part by the oligosaccharide head groups (blue) of these glycosphingolipids. The same three oligosaccharides are also found attached to certain blood proteins of individuals of blood types O, A, and B, respectively. (Fuc represents the sugar fucose 海藻糖.) N-acetyl-D-galactosamine D-galactose

Pathways for the breakdown of GM1, globoside, sphingomyelin to ceramide (lysosomal hydrolases) Tay-Sachs disease—GM2 accumulates in brain and spleen—progressive retardation in development, paralysis（瘫痪）, blindness and death by the age of 3 or 5 yrs

Pathways for the breakdown of GM1, globoside, sphingomyelin to ceramide (lysosomal hydrolases) Fabry’s disease, Gaucher’s disease Sandhoff’s disease

Pathways for the breakdown of GM1, globoside, sphingomyelin to ceramide (lysosomal hydrolases) Any defects in any of these enzymes lead to accumulation of gangliosides in cells—diseases such as Niemann-Pick diseases (sphingomyelin accumulates in brain, spleen, liver-mental retardation.

EM of a brain from a infant with Tay-Sachs disease—abnormal deposits of gangliosides in lysosomes

3.3胆固醇是真核生物中常见的第三类膜脂 3.3.1胆固醇有一个由4个稠环组成的环形核－环戊烷多氢菲。其中3个环是6碳环（A、B和C环），一个环是5碳环（D环） 3.3.2胆固醇分子中C-3处有一个羟基，这也是称之"醇"的缘故。另外分子中的C-10和C-13处都连有甲基，同时一个8碳的侧链连接在C-17上。3.3.3胆固醇可以由哺乳动物细胞合成，它不仅是某些膜的成分，而且也是类固醇激素和胆酸盐的前体。

Sterols—structural lipids in membranes of most eukaryotic cells. Steroid nucleus—four fused rings—3 six carbon, 1 five carbon. Cholesterol_ rings A-D. At C3, there is a hydroxyl group (OH) as the head polar group. It condenses with fatty acids to form a sterol ester for storage and transport

Bile acids are poplar derivatives of cholesterol that acts like a detergents（清洁剂） in the intestine, emulsifying dietary fats to make them readily accessible to digestive lipases.

3.3.4 在植物和真菌中也能发现固醇类似物 3.3.5 细菌一般没有固醇. 3.3.6胆固醇也是类固醇激素和胆酸盐的前体。类固醇激素包括睾酮（雄性激素）和雌二醇（雌性激素之一）以及醛固酮（来自肾上腺，调节盐分泌）。 (fig.). 3.3.7 许多 Nobel Prizes获得者都于胆固醇的研究有关

3.4 磷脂酶A1和A2分别特异地催化甘油磷脂中C-1和C-2位置酯键的水解。由磷脂酶A作用产生的高浓度的溶血磷脂（lysophosphoglycerides）可能会破坏细胞膜，其它两种磷脂酶C和D，磷脂酶C催化甘油和磷酸之间的键的水解，释放出二脂酰甘油，磷脂酶D催化甘油磷脂水解生成磷脂酸。

Specificity of phopholipases (mostly in lysosomes) Ester bonds Phosphodiester bonds Phosphatidylinositol 4,5 bisphosphate

5. 一些脂具有特别的生物学作用. 5.1 胆固醇是淄类激素的前体 5.1.1 男性荷尔蒙是男性第二性征出现

第 2 章脂类 Lipids