Chapter 8
Lipids and Proteins Are Associated in
Biological Membranes
生化科吳嘉霖老師第一醫學大樓0859室校內分機：5159 What is a Lipid
Lipids: a heterogeneous class of naturally occurring organic
compounds classified together on the basis of common solubility
properties
•  insoluble in water, but soluble in aprotic organic solvents
including diethyl ether, chloroform, methylene chloride, and
acetone
•  Amphipathic （雙極性） in nature
Lipids include:
• Open Chain forms
•  fatty acids, triacylglycerols, sphingolipids,
phosphoacylglycerols, glycolipids,
•  lipid-soluble vitamins（A,D,E,K)
•  prostaglandins, leukotrienes, and thromboxanes
• Cyclic forms
•  cholesterol, steroid hormones, and bile acids
Fatty Acids
•  Fatty acid: an unbranched-chain carboxylic acid, most commonly of 12 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or
phosphodiacylglycerols of biological membranes
親水端疏水端 Fatty Acids
Length of fatty acid plays a role in its chemical character"
• Usually contain even numbers of carbons (can contain odd,
depending on how they are biosynthesized)"
• FA that contain C=C, are unsaturated(不飽和）: If contain only
C-C bonds, they are saturated（飽和）
Fatty Acids
•  In most unsaturated fatty acids, the cis(順式） isomer
predominates; the trans（反式） 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
Triacylglycerols（三酸甘油脂）
•  Triacylglycerol (triglyceride): an ester of glycerol with three
fatty acids
•  Triacylglycerol通常聚集在脂肪組織中，脂肪酸儲存的主要方法。
•  natural soaps are prepared by boiling triglycerides
(animal fats or vegetable oils) with NaOH, in a
reaction called saponification (Latin, sapo, soap)
Soaps
·• 生物體外用脂肪酸與鹼（如
NaOH)作用稱
saponification(皂化反應）
·• 生物體想利用脂肪酸時，
Triacylglycerol會被lipases水解 •  Soaps form water-insoluble
salts when used in water
containing Ca2+, Mg2+ (hard
water)-硬水中的Ca2+, Mg2+會
和脂肪酸反應產生沈澱 Soap
Phosphoacylglycerols (Phospholipids)-磷脂質
•  When one alcohol group of glycerol is esterified by a
phosphoric acid rather than by a carboxylic acid,
phosphatidic acid（磷脂酸） produced
•  Phosphoacylglycerols (phosphoglycerides) are the second
most abundant group of naturally occurring lipids, and they
are found in plant and animal membranes(細胞膜的主要成分）
Phosphoacylglycerols
Waxes（蠟）
•  A complex mixture of esters of long-chain carboxylic
acids and alcohols
•  Found as protective coatings for plants and animals（存在於植物的莖、葉、果實、動物毛皮、羽毛）
棕櫚蠟的主要成份鯨魚產生的蠟 Sphingolipids（神經鞘脂質）
•  Contain sphingosine, a longchain amino alcohol
sphingosine
•  Found in plants and animals
•  Abundant in nervous system
（神經系統含量特別豐富）
•  Bares structural similarity to
phospholipids
主要存在於神經系統之細胞膜內 Multiple sclerosis(多發性硬化症）
Myelin sheath: 70 - 85% lipids and about 15 – 30% proteins
Glycolipids(細胞膜上的標記）
•  Glycolipid: a compound in
which a carbohydrate is
bound to an -OH of the lipid
•  In most cases, sugar is
either glucose or galactose
•  many glycolipids are
derived from ceramides
•  Glycolipids with complex
carbohydrate moiety that
contains more than 3
sugars are known as
gangliosides（神經苷脂類：
含三個以上醣基）
葡萄糖腦苷脂 Gangliosides（神經苷脂類：含三個以上醣基）
Steroids（類固醇）
•  Steroids: a group of lipids that have fused-ring
structure（融合環結構） of 3 six-membered rings, and
1 five-membered ring.
膽固醇睪固酮雌二醇黃體激素 Sex Hormones
•  Androgens(雄激素）: male sex hormones
•  synthesized in the testes
•  responsible for the development of male secondary
sex characteristics
•  Testosterone
•  Estrogens(雌激素）: female sex hormones
•  synthesized in the ovaries
•  responsible for the development of female secondary
sex characteristics and control of the menstrual cycle
Cholesterol(膽固醇）
•  The steroid of most interest in our discussion of
biological membranes is cholesterol
Biological Membranes
•  Every cell has a cell membrane (plasma membrane)
•  Eukaryotic cells also have membrane-enclosed organelles
(nuclei, mitochondria…etc)
•  Molecular basis of membrane structure is in lipid
component(s):
•  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（疏水性作用力）
•  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)
Lipid Bilayers
•  The polar surface of
the bilayer contains
charged groups
•  The hydrophobic
tails lie in the interior
of the bilayer
Effect of Double Bonds on the
Conformations of Fatty Acids
•  Kink(扭結） in
hydrocarbon chain and
causes disorder in
packing against other
chains
•  This disorder causes
greater fluidity in
membranes with cisdouble bonds （碳=碳
雙鍵增加細胞膜流動性）
Biological Membranes
•  Plant membranes have a higher percentage of
unsaturated fatty acids than animal membranes
•  The presence of cholesterol is characteristic of
animal rather than plant membranes
•  Animal membranes are less fluid (more rigid) than
plant membranes（排列整密加上膽固醇的存在）
•  The membranes of prokaryotes, which contain no
appreciable amounts of steroids, are the most fluid
Cholesterol reduces Fluidity
•  Presence of cholesterol
reduces fluidity by
stabilizing extended
chain conformations of
hydrocarbon tails of FA
(細胞膜內的膽固醇的存
在使得細胞膜變得較不
具流動性)
膽固醇本身融合環結構很
堅固，並可藉由凡得瓦力
穩定飽和脂肪酸伸展的長
直鏈排列。 Membrane Layers
•  Both inner and outer
layers of bilayer contain
mixtures of lipids
•  Compositions on inside
and outside of lipid
bilayer can be
different(外層空間較大，
有較高濃度的大分子）
Temperature Transition in Lipid Bilayer
• 加熱會使排列規則的脂質雙層膜變得不規則 • Mobility of the lipid chains increases dramatically
Q&A
Membrane Proteins
•  Functions: transport substances across membranes; act as
receptor sites, and sites of enzyme catalysis
•  Peripheral proteins（周邊蛋白質）
•  bound by electrostatic interactions
•  can be removed by raising the ionic strength
•  Integral proteins（嵌入蛋白質）
•  bound tightly to the interior of the membrane
•  can be removed by treatment with detergents or
ultrasonification
•  removal generally denatures them
Integral and Peripheral proteins
Peripheral
protein
Certain Proteins are anchored to
membrane by lipid anchors
•  N-myristoyl- and S-palmitoyl anchoring motifs
Fluid Mosaic Model
•  Fluid: there is lateral motion of components in the membrane;
•  proteins, for example, “float” in the membrane and
can move along its plane
•  Mosaic: components in the membrane exist side-by-side as
separate entities
•  the structure is that of a lipid bilayer with proteins,
glycolipids, and steroids such as cholesterol
embedded in it
•  no complexes, as for example, lipid-protein
complexes, are formed
Fluid Mosaic Model of Membrane Structure
Freezefracture(冷凍破
裂膜技術）
Membrane Function: Membrane Transport
•  Passive transport（被動運輸）
•  driven by a concentration gradient（高濃度往低濃度）
•  simple diffusion: a molecule or ion moves through an
opening (non charged molecules)
•  facilitated diffusion: a molecule or ion is carried across a
membrane by a carrier/channel protein ex. Glucose
permease
•  Active transport（主動運輸）-耗能 •  a substance is moved against a concentration gradient（低
濃度往高濃度）
•  primary active transport: transport is linked to the
hydrolysis of ATP or other high-energy molecule; for
example, the Na+/K+ ion pump
•  secondary active transport: driven by H+ gradient ex.
Galactoside permease
Passive transport (simple diffusion)
Simple diffusion: a molecule or ion moves through an
opening (non charged molecules)
Passive transport (facilitated diffusion)
•  Passive diffusion of species (uncharged) across
membrane dependent on concentration, presence
of carrier protein
葡萄糖通透酶 Active transport (primary active transport)
水解蛋白質上磷酸
根後，構型回復 K＋：細胞內>細胞外
Na+:細胞外>細胞內
蛋白質接上磷酸根
導致蛋白質構型改
變並可與Na＋結合
，打開離子孔洞。 Na+/K+ ion pump
Active transport (secondary active transport)
細胞外高濃度H+離子
驅使乳醣（lactose)進
入細胞內 Galactoside permease（半乳醣苷滲透酶）
How do member receptors work
LDL在細胞內釋
出膽固醇，過度
供應膽固醇會抑制
LDL受體蛋白合成 Lipid-Soluble Vitamins
•  Vitamins are divided into two classes: lipid-soluble and water-soluble
Vitamin A（和視覺有關）
•  Vitamin A (retinol) occurs only in the animal world
•  Extensively unsaturated hydrocarbon (β-carotene, β-胡蘿蔔素)
Vitamin A
•  The best understood role of Vitamin A is its participation in the
visual cycle in rod cells
•  the active molecule is retinal (vitamin A) retinal forms an imine
with an -NH2 group of the protein opsin（視蛋白） to form the
visual pigment called rhodopsin（視紫質）
•  Night Blindness（夜盲症），表現為在黑暗中或光線較弱的地方看
不清東西 Vitamin D（和鈣質吸收有關）
•  A group of structurally related compounds that are involved in the
regulation of calcium and phosphorus metabolism
•  the most abundant form in the circulatory system is vitamin D3
•  Rickets(佝僂病）：缺乏維生素D導致骨頭變軟而變形調節腸道
吸收鈣和磷 Vitamin E（良好的抗氧化效果）
•  The most active of vitamin E is α-tocopherol (α-生育醇，在大鼠中
為生殖所必須）
•  Vitamin E is an antioxidant（抗氧化劑），本身為一良好還原劑，可在
氧化劑與其他生物分子作用前先與之反應。亦可與細胞內自由基
（free radicals）反應並加以清除。 Vitamin K（修飾凝血酶原Prothrombin)
•  Vitamin K
(koagulation)has an
important role in the
blood-clotting process
•  Long unsaturated
hydrocarbon side consists
of repeating isoprene
units
Vitamin K
dicumarol & warfarin(抗凝血劑）：維生素K的拮抗劑 Prostaglandins（前列腺素）
•  Prostaglandins: a family of compounds that have the 20carbon skeleton of prostanoic acid
•  First detected in seminal fluid…from prostate
•  The metabolic precursor is arachidonic acid,花生四烯酸 (20
carbon atoms: 4 double bonds)
•  Production of prostaglandins from arachidonic acid occurs in
several steps.
Prostaglandins: 控制血壓、刺激平滑肌收縮、導致發炎、
抑制血小板凝集 Aspirin、cortisone: 抑制Prostaglandins合成，可抗發炎 Arachodonic Acid and Some Prostoglandins
Leukotrienes（白三烯素）
• Compounds also derived from arachidonic acid
• Found in white blood cells (leukocytes)
• Consists of 3 conjugated double bonds
• An important property is constriction of smooth muscles,
especially in the lungs（刺激肺中平滑肌收縮）
Leukotriene C
利用抑制Leukotrienes
合成的藥物治療氣喘 Thromboxanes (凝血素）
第三類arachidonic acid
衍生物，與血小板凝
結及平滑肌收縮有關