9

Slide1: 

Metabolism of lipid 1.summarize • characteristics • classification

Slide4: 

• nomenclature

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• essential fatty acid for nutrition purpose

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• physiological functions

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2. digestion & absorption • in the small intestine • need bile salt

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• the characteristics of lipid digestion

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3. the transportation of lipids in blood stream ( lipoprotein)

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• the components & contents a. the kinds

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血脂 甘油三酯 磷脂 胆固醇 脂肪酸 胆固醇酯 游离胆固醇 磷脂酰胆碱 磷脂酰乙醇胺 神经鞘磷脂 半酯化脂肪酸 酯化脂肪酸

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b. The importance

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• lipoprotein concept components & classification

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according the behavior of electrophoresis or density centrifugation

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电泳法 乳糜微粒 前B-脂蛋白 B-脂蛋白 a-脂蛋白 电泳位置 原 a2球 B-球 a球 密度法 CM VLDL LDL HDL 密度 颗粒大小 TG 胆固醇 磷脂 生成部位 功能 ++++ +++ + + + + ++ +++ ++ +++ 肠 肠、肝 血浆 肝、肠 运输外源TG 运输内源TG 运输胆固醇到全身 运输全身胆固醇到肝 ++

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b. the structure of lipoprotein

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c. apolipoproteins concept kinds synthetic site function

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• the function & metabolism of lipoprotein in blood

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a. CM synthesis transportation metabolism function

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capillary CM mature CM hydrolyze TG in CM ApoC-Ⅱ ApoE activated （activated （recognized LPL of LPL ) by CMR recept) FA HDL CMR liver return ApoC- Ⅱ

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characteristics b. VLDL synthesis transportation metabolism function

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LPL activated VLDL hydrolysis TG in VLDL ApoC-Ⅱ ApoE FA utilization ApoC-Ⅱ、 cholesterol or storage lecithoid in extrahepatic tissues HDL IDL cholesterol ester   LDL（ rich of ester cholesterol)

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characteristics c. LDL synthesis characteristics metabolism function

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LDLin blood LDL receptor in tissue Recognized & binded by ApoB,E in LDL entered into tissue lysosome enzyme cholesterol fatty acid ApoB、 E break down

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Cholesterol in cell: Utilized control of metabolism of cholesterol Lack of LDL receptor ----- familial hypercholesterolemia

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d. HDL synthesis function metabolism

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LCAT in blood Liver HDL HDLin blood CH in HDL cell （ApoA、E、 （dishing） esterify C、D） （ CH、lecithoid） ApoC、E ApoC- Ⅱ CM、VLDL HDL synthesized mature HDL in intestine （globular） C CE  IDL taken by liver

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Function of HDL 3 points

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hyperlipoproteinemia concept the primary affection （ receptor,enzyme,Apo) the secondary affection (diabetes,liver,kidney,thyroid fatness)

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高脂血症 概念：空腹胆固醇>6mmol/L TG>2.26mmol/L 高脂血症=高脂蛋白血症 脂类代谢异常 高脂血症 心血管疾病 LDL、胆固醇 与 动脉硬化 正相关 HDL 与动脉硬化 负相关 （保护因子） 如LDL HDL 则危险性

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4. Intermediately metabolism of TG • catabolism of TG

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a. mobilization of TG concept characteristics

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limited enzyme triglyceride lipase ( hormone sensitive lipase)

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1) lipolytic hormone 2) antilipolytic hormone (insulin)

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b. Oxidative catabolism of fatty acid characteristics

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• -oxidation a. evidence

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Even carbon atoms β α C6H5-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH   C6H5—CH2-COOH（苯乙酸）+Gly (苯乙尿酸)

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Odd carbon atoms β α C6H5-CH2-CH2-CH2-CH2-CH2-CH2-COOH   C6H5—COOH（苯甲酸）+Gly ( 马尿酸)

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b. preparation 1) activation of fatty acid substrate: cofactors: enzyme: reaction site :

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Product: fatty acyl-CoA Process:

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2) transported into mitochondria the carrier-------carnitine enzyme:

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（CH3）3-N-CH2-CH-CH2-COOH OH the formula of carnitine

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3) -oxidation of saturated fatty acid 4 steps:

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a. dehydrogenation(FAD) b. hydration c. dehydrogenation (NAD+) d. thiolysis

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acetyl-CoA enter the TCA cycle

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the energy release & utilization

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Palmitate(16C) for instance 73ATP（NADH+H+）=21ATP [7  2.5ATP （NADH+H+）=17.5ATP ] 7  2ATP（FADH2）=14ATP [7  1.5 ATP（FADH2）= 10.5ATP] net yield 129ATP or 106ATP 8  12ATP(acetyl-CoA)=96 ATP [8  10ATP(acetyl-CoA)= 80 ATP] Total yield: 131ATP or 108 ATP

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C. the synthesis & utilization of ketone bodies

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fatty acid heart,muscle liver B-oxidation B-oxidation thorough oxidative catabolism of Acetyl-CoA Acetyl-CoA small part Large part oxidative catabolism acetone acetoacetate B-hydroxybutyrate acetoacetate

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• concept • the advantages and disadvantages of ketone bodies for human body

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• The reasons of elevate the level of blood ketone bodies

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hunger , diabetes fat mobilization elevate of ketone bodies ketone bodies synthesis > utilization ketonemia ketonuria

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a. the synthesis of ketone bodies 1) site 2) substrate 3) process

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4) enzymes thiolase * HMG-CoA synthetase HMG-CoA lyase  -hydroxybutyrate dehydrogenase

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the utilization of ketone bodies 1) site 2) process

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4) enzymes 5) product

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c. Oxidation of glycerol

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甘油三酯 甘油三酯脂肪酶 甘油 脂肪酸 甘油激酶 氧化 a-磷酸甘油 脂肪酸的活化 脂酰CoA合成酶 消耗ATP 脂肪酸进入线粒体（肉毒碱） 脂肪酸的B氧化 脱氢（FADH2) 加水 再脱氢（NADH+H) 硫解（乙酰辅酶A) TCA循环 肝酮体生成 磷酸二羟丙酮 糖异生 氧化分解 NADH+H

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• synthesis of TG a. synthesis of fatty acid

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1) site 2) substrate 3) process

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acetyl CoA enter cytosol

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1 2

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synthesis of malonyl-CoA Key enzyme: Acetyl-CoA carboxylase

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Palmitate synthesis , for instance 1) site 2) materials 3) enzyme

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ACP

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b.biosynthesis of TG intestine：food MG TG lipocyte： G MG TG liver： G MG TG 1) site

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2) materials 3) process

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c. regulation of biosynthesis & catabolism of fatty acid

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Adipose tissue insulin LPL activated Induced promote Acetyl CoA carboxylase、 Fatty acid synthetase α-P-glycerol + fatty acid Fatty acid in CM、VLDL Promotion of synthesis of TG phosphotidate enter Fat tissue promote Synthesis of TG

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glucagon inhibition Acetyl CoA carboxylase inhibition synthesis of fatty acid,、TG

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5. metabolism of phospholipids 1) Structure & classification

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FA glycerol FA phosphate X

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According to the core glycerophospholipids sphingolipids

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According to the X group Phosphatidy choline Phosphatidy ethanolamine Phosphatidy serine Phosphatidy inositol

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FA glycerol FA phosphate X

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2) Metabolism of phospholipids a. catabolism

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2) products 3) process 1) enzyme

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b . anabolism * lysophospholipid 1) site

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2) process de nove synthesis salvage synthesis

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* Phosphatidic acid

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the importance of Phosphocholine

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choline Phosphocholine + DG phosphatidyl choline VLDL Transportation of TG In liver Synthesis TG in liver Fatty liver FA

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The causes of fatty liver inbanlance in the rate of TG formation and export starvation or diabetes , fat mobilization LPL hydrolysis of TG in lipoprotein formation,secret of VLDL < fatty acid infiltration in liver

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2、Metabolic block in the production of plasma lipoprotein apoprotein lipoprotein phospholipids provision secretory mechanism

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3 、ethanol CH3-CH2-OH CH3-CHO NAD+ NADH+H+ NADH+H+ fatty acid oxidation hepatic fatty acid synthesis

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4. deficiency of choline 5. Vit E

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the importance of Phospholipids

6.metabolism of cholesterol: 

6.metabolism of cholesterol characteristics a. anabolism

1) site: 

1) site 2) materials 3) process

Slide118: 

synthesis of mevalonate synthesis of squalene synthesis of cholesterol 3 stage:

Key enzymeHMG-CoA reductase: 

Key enzyme HMG-CoA reductase

Slide121: 

MVA 5-P MVA IPP （5C） （6C） ATP CO2 DPP （5C） IPP+DPP geranylpyrophosphate（10C） + IPP farnesylpyrophosphate（15C） 2 farnesylpyrophosphate squalene NADPH+H+

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5) traits 6) regulations of cholesterol biosynthesis ( HMG-CoA reductase)

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food Hormone insulin thyroid hormone glucagon bile acid drugs

7 ) cholesterol has several  fates: 

7 ) cholesterol has several fates cholesterol Vitamin D bile acid Steroid hormones excrete