CHAPTER 08 Lipid

8-1 What Are the Structures and Chemistry of Fatty Acids?

 Classes of lipids (all biological lipids are amphipathic)
1. the lipids found in biological systems are either hydrophobic or amphipathic
2. Lipid class：fatty acids、triacylglycerols、glycerophospholipids、sphingolipids、waxes、isoprene-
based lipids(including steroids)
 Storage lipids：fatty acids, triacylglycerol, wax
 Structural lipids in membranes：phospholipids, glycolipids, cholesterol
 Lipids as signal, cofactors and pigments
 Biological function of lipids
3. The structure of amphipathic lipids form
when added to aqueous solution
 monolayer
 bilayer (liposome)
 micelle
 Fatty acids
1. A fatty acid is composed of a long hydrocarbon chain and a terminal carboxyl group
2. Fatty acids occur in large amounts in biological systems
3. The simplest lipids：the constituent of many more complex lipids
4. Short and medium chain FAs are amphipathic and partially soluble in water
5. Long chain fatty acids are highly insoluble in water
6. Most of the fatty acids found in nature have an even number of carbon atoms
7. Branched and primary in bacteria
8. Fatty acids are either saturated or unsaturated
飽和脂肪酸不容易反應，不飽和脂肪酸因為有 pi 電子，因此容易反應
 Saturated chains pack tightly and form more rigid, organized aggregates
 Unsaturated chains bend and pack in a less ordered way, with greater potential for motion
飽和脂肪酸的名稱結尾是-anoic acid；不飽和脂肪酸的名稱結尾為-enoic acid
不飽和脂肪酸的表達為總碳數:雙鍵數目
 Some fatty acids are not synthesized by mammals and yet are necessary for growth and life
 These essential fatty acids include linoleic and 𝛾-linolenic acids

9. Melting point of fatty acids

 determined by chain length of fatty acid、degree of unsaturation of fatty acid
number of carbon increasing, melting point increasing
 number of double bound increasing, melting point decreasing
 Fatty acid 的順反判斷
1. Most unsaturated fatty acids in nature are cis fatty acids
2. 順式：cis, Z form；反式：trans, E form
3. 反式脂肪酸對人體不易分解，因此容易造成堆積
 命名：
1. Common name、systematic name
2. IUPAC：不飽和鍵碳號-順反式-總碳數-不飽和鍵碳號-enoic acid/anoic acid
3. 編碼：總碳數:幾個不飽和鍵:不飽和鍵碳號
4. Δ 代表正著數(從 COOH 開始)、ω 代表倒著數(從 COOH 另一端開始)
5. 範例：
18:2 Δ9,12 20:5 Δ5,8,1114,17
18:2 ω-6 20:5 ω-3
18:2 n-6 20:5 n-3
22:6 Δ4,7,10,13,16,19 22:1 Δ11
22:6 ω-3 22:1 ω-11
22:6 n-3 22:6 n-11
11Z-Docosa-11-enoic acid
6.補充：脂肪酸之代謝，僅在同 n 族(或 ω 族)間 可互變，不同族之間不可互變
n-6 族脂肪酸 →→→ 其它 n-6 族脂肪酸
n-3 族脂肪酸 →→→ 其它 n-3 族脂肪酸
 重點：命名、結構、常見脂肪酸、物理特性
8-2 What Are the Structures and Chemistry of Triacylglycerols?
 The structure of triacylglycerols
1. Triacylglycerols (TGs) are a major energy reserve and the principal neutral derivatives of glycerol
found in animals
2. These molecules consist of a glycerol esterified with three fatty acids (3glycerol +3 fatty acids →
triglyceride)
3. Fatty acids of triacylglycerols usually vary：
 fatty acid on carbon 1 is usually saturated
 fatty acid on carbon 2 usually unsaturated (double bond)
 fatty acid on carbon 3 can be either (但通常是接上飽和脂肪酸)
 unsaturated fatty acids decrease Tm (fat with high saturated fatty acids, Tm >20; but oil with high
unsaturated, Tm < 20)

 Function of triacylglycerols
1. Triacylglycerols in animals are found primarily in the adipose tissue, where it serves as a depot or
reservoir of stored energy
2. Most natural plant and animal fat is composed of mixtures of simple and mixed triacylglycerols
3. Energy production oxidation of fatty acid to generation of ATP
4. Heat production by brown adipose tissue oxidation
5. Insulation (thermal insulator cushion 阻熱)
6. Hydrolysis with alkali is called saponification and yields salts of free fatty acids and glycerol
8-3 What Are the Structures and Chemistry of Glycerophospholipids?
 Overview
1. Lipid classification
 Simple lipids：fats、waxes
 Complex lipids：phospholipids (glycerophospholipids、sphingophospholipids)、glycolipids、other
complex lipids
 Precursor and derived lipids
 Biological membranes
1. Lipid bilayers, amphipathic lipids (both eukaryotic and prokaryotic cells share the same properties)
2. Chemical asymmetry of composition
3. Dynamic structure allowing cell movement
4. Lipids are major components of membranes (不同胞器組成的脂肪分子不同)
 phospholipids (磷脂)：glycerophospholipid (甘油磷脂)、sphingophospholipid (神經鞘磷脂)
 glycolipids (醣脂)：glycosphingolipids (醣神經胺醇脂)、glycoglycerolipid (醣甘油脂)
 sterol：cholesterol (固醇)→非脂質，與細胞通透有關
 Glycerophospholipids Are the Most Common Phospholipids
1. Phosphatidic acid (PA), the parent compound for the glycerol-based phospholipids, consists of sn-
glycerol-3-phosphate, with fatty acids esterified at the 1- and 2-positions
2. Phosphatidic acid (PA) is the simplest membrane of glycerophospholipid
3. Phosphatidic acid + various head group → various glycerophospholipid

 Phosphatidic acid + H 形成 phosphatidic acid

 Phosphatidic acid + inositol (醣類)可以形成 phosphatidylinositol (PI)，作為訊息傳遞訊號
 Phosphatidic acid + ethanolamine 可以形成(胺類)可以形成 phosphatidylethanolamine (PE)
 Phosphatidic acid + serine 形成 phosphatidylserine，與細胞凋亡有關
 Phosphatidic acid + glycerol 可以形成 phosphatidylglycerol (PG)
 Phosphatidic acid + choline 形成 phosphatidylcholine (PC)，俗稱卵磷脂(lecithin)，是細胞膜含
量最高的 Phospholipids
 Phosphatidic acid + phosphatidyl-glycerol 形成 cardiolipin，出現在 complex III 上面綁住
cytochrome c，in mitochondrial inner membrane，是細胞 apoptosis 的重要物質\

 cardiolipin
1. 粒線體內有很多 cytochrome c, 作為 complex III 的電子接受者
2. Cardiolipin 可以固定 complex III in normal
3. 但是當 cardiolipin 被體內的自由基氧化後，會使 binding 能力下降→cytochrome C 排出細胞→
產生 ROS 或細胞凋亡反應
 PIP2 secondary messenger system
1. Hormone 與 receptor 結合→GTP 活化 phospholipase C→切斷 PIP2 的磷酸鍵，形成 DAG 與 IP3
→IP3 與內質網上的 receptor 結合→活化鈣離子通道產生 second messenger→DAG 與 protein
kinase C 作用→產生下游磷酸化的反應

 Some phospholipids have ether-linked fatty acids

1. Ether glycerophospholipids possess an ether linkage at the C-1 position of glycerol
 platelet-activating factor, or PAF
A. The alkyl group at C-1 of PAF is typically a 16-carbon chain, but the acyl group at C-2 is a 2-
carbon acetate unit
B. PAF is much more water soluble than other, allowing PAF to function as a soluble messenger
in signal transduction
C. platelet aggregation, dilation of blood vessels, mediator in inflammation, allergic responses,
and toxic shock syndrome
 Plasmalogens：for phospholipase resistance

8-4 What Are Sphingolipids, and How Are They Important for Higher Animals?

 分類：
1. Sphingolipids represent another class of lipids frequently found in biological membranes
2. 神經鞘氨醇(Sphingosine)為基底，第二個碳上接胺基，可與脂肪酸結合
3. 可以分成以下兩類：sphingomyelin (神經磷脂)、glycolipids
 Ceramide (神經醯胺)
1. a fatty acid is joined to a sphingosine via an amide linkage on amino group to form a ceramide
2. Sphingomyelin is formed by the esterification of a phosphorylcholine or a phosphorylethanolamine
to the 1-hydroxy group of a ceramide

 Glycosphingolipids (glycolipids)

1. they consist of a ceramide with one or more sugar residues in a 𝛽 -glycosidic linkage at the 1-
hydroxyl moiety
2. cerebrosides (monoglycosyl ceramides)：galactosylcerebrosides、glucosylcerebrosides
 neutral glycosphingolipids
 single glucose or galactose is bound in this manner
3. globosides (with 2 or more sugars)
4. gangliosides (with one or more sialic acid)：
 these being a sialic acid such as N-acetylneuraminic acid
 acidic glycosphingolipids, and they have a net negative charge at neutral pH
 Gangliosides are present in nerve endings and are important in nerve impulse transmission

5. Tay–Sachs disease
 genetically transmitted diseases involve the accumulation of specific glycosphingolipids due to an
absence of the enzymes (Hesosaminifase) needed for their degradation
 ganglioside GM2 in the brains of Tay–Sachs disease victims, a rare but fatal childhood disease
characterized by a red spot on the retina gradual blindness, and self-mutilation
 患者可以看見 lysosome 肥大
6. Sphingolipids at cell surface are sites of biological recognition：
 prominent in the plasma membranes of neurons
 ABO blood group antigens
 sphingomyelin as important component in nervous tissue (myelin sheath)
 some gangliosides promote the growth of neural tissue in cell culture (promote regeneration of
nerve tissue after spinal cord injury)
 membrane sphingolipids serve as sources of intracellular messengers
8-5 What Are Waxes, and How Are They Used?

 Structure of wax
1. Waxes are esters of long-chain alcohols with long-chain fatty acids
 Function and characteristic of wax
1. Melting point 60-100℃
2. Completely water-insoluble as water repellent in feather, leaves
3. As energy store in some marine microorganisms
4. Biological waxes and pharmaceutical/cosmetic industries
8-6 What Are Steroids, and What Are Their Cellular Functions? (詳細代謝會在 CHAPTER24 講解)
 Cholesterol
1. Common structural motif of three 6-membered rings and one 5-membered ring all fused together
2. Polymers of five-carbon isoprene units
3. Isoprene units can be linked in terpenes to form straight-chain or cyclic molecules, and the usual
method of linking isoprene units is head to tail
4. Many steroids contain an oxygen at C-3, either a hydroxyl group in sterols or a carbonyl group in
other steroids
5. Cholesterol is a principal component of animal cell plasma membranes, and smaller amounts of
cholesterol are found in the membranes of intracellular organelles
6. The weakly polar alcohol group at the C-3 position have important consequences for the properties
of plasma membranes

 Steroid Hormones Are Derived from Cholesterol

1. Steroids derived from cholesterol in animals include five families of hormones (the androgens,
estrogens, progestins, glucocorticoids, and mineralocorticoids) and bile acids
2. Steroid hormone serve many functions in animals including salt balance, metabolic function and
sexual functions
8-7 Membrane
 Membrane fluidity
1. 影響細胞膜流動性的三大因素：溫度、膽固醇、脂肪酸的飽和度
 2. 溫度：因為 Ek ∝ T，當溫度越高，分子動能越大，細胞膜的流動性上升
3. 膽固醇：膽固醇本身會增加細胞膜的穩定性，
低溫情況加入膽固醇：因為低溫時脂肪酸的運動程度低，加上膽固醇行促進脂肪酸的間距
拉大，導致流動性上升
高溫情況加入膽固醇：膽固醇會讓 lipid 之間相黏，導致流動性下降
4. 飽和度：飽和脂肪酸會導致細胞流動性下降，不飽和脂肪酸會增加流動性
 Membrane function：dynamics and fusion

1. Passive Diffusion
 passive diffusion of an uncharge species across a membrane depends only on the concentrations
on the two sides of the membrane
 the passive diffusion of a charged species across a membrane depends on the concentration and
also on the charge of the particle (Z) and the electrical potential difference across the membrane
1. Fatty acid 的 carbon skeleton 為(A)26:0 (B)16:0 (C) 20:4;5,8,11,14 (D) ω9, C18:1 請問 melting point 排序
2. 下列何者為不飽和之環狀脂肪酸? (A)Linoleic acid (B)Oleic acid (C) Chaulmoogric acid (D) Arachidonic
acid
3. 下列何者為不飽和之環狀脂肪酸? (A)Dodecanoic acid (B)Tetradecanoic acid (C)Teracosanoic acid (D)
15- Teracosanoic acid
4. 下 列 何 種 脂 質 是 屬 於 神 經 鞘 脂 質 (sphingolipids)? (A)lecithin (B)ceramide (C)phosphatidylserine
(D)prostaglandin
5. 下列何這不是 sphingomyelin 的組成物質? (A)choline (B)fatty acid (C)glycerol (D)sphingosine