1

Metabolism of lipid

1.summarize

• characteristics

• classification

2

3

4

• nomenclature

5

6

• essential fatty acid for

nutrition purpose

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• physiological functions

8

2. digestion & absorption

• in the small intestine

• need bile salt

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10

• 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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a. 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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20

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 CMApoC- ApoE activatedⅡ（ 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- ApoE FA utilizationⅡ 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 bloodLiver 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 （ globula

r ） 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

37

38

limited enzyme

triglyceride lipase

( hormone sensitive lipase)

39

40

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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54

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4) acetyl-CoA enter the TCA

cycle

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5) the energy release &

utilization

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Palmitate(16C) for instance 73ATP （ 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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61

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-hydroxybutyrateacetoacetate

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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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b. 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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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

101

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

109

choline

Phosphocholine + DG phosphatidyl choline

VLDL

Transportation of TG

In liver

Synthesis TG in liver

Fatty liver

FA

110

The causes of fatty liver

1. 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

111

2 、 Metabolic block in the production of

plasma lipoprotein

apoprotein

lipoprotein

phospholipids provision

secretory mechanism

112

3 、 ethanol

CH3-CH2-OH CH3-CHO

NAD+ NADH+H+

NADH+H+ fatty acid oxidation

hepatic fatty acid synthesis

113

4. deficiency of choline

5. Vit E

114

• the importance of

Phospholipids

115

116

6.metabolism of cholesterol

characteristics

a. anabolism

117

1) site

2) materials

3) process

118

synthesis of mevalonate

synthesis of squalene

synthesis of cholesterol

3 stage:

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120

4) Key enzyme

HMG-CoA reductase

121

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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123

5) traits

6) regulations of

cholesterol biosynthesis

( HMG-CoA reductase)

124

foodHormone

insulin

thyroid hormone

glucagon bile acid

drugs

125

7 ) cholesterol has several fates

cholesterol Vitamin D bile acid

Steroid hormones

excrete