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第 5 章. 脂类代谢. Metabolism of Lipid. 脂类概述. 定义 :. 脂肪和类脂总称为脂类 (lipids ) 。. 分类 :. 三脂酰甘油 (triacylglycerol, TAG) , 也称为 甘油三酯 (triglyceride, TG). 脂肪 (fat). 胆固醇 (cholesterol, CHOL) 胆固醇酯 (cholesterol ester, CE) 磷脂 (phospholipid, PL) 糖脂 (glycolipid) 鞘脂 (sphingolipid). 类脂 (lipoid).

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第 5 章

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5

5

Metabolism of Lipid


5

  • :

(lipids)

  • :

(triacylglycerol, TAG) (triglyceride, TG)

(fat)

(cholesterol, CHOL)

(cholesterol ester, CE)

(phospholipid, PL)

(glycolipid)

(sphingolipid)

(lipoid)


5

  • (fatty acids)

  • ,(saturated fatty acid)(unsaturated fatty acid)

  • (essential fatty acid)


5

FA

FA

FA

FA

FA

Pi

X

FA

(phosphoglyceride)

X=


5

X=


5

FA

FA

Pi

X

FA


5


5

The Classification and Naming of Unsaturated Fatty Acids


5

  • n


5

(n)


5

  • 10

  • 20


5

(CH3-COOH)(-CH2-)

2.

  • (monounsaturated fatty acid)

  • (polyunsaturated fatty acid)


5

w-3w-6w-7w-9

-6-3-6-9-9-7-6-3


5

5-1


5

Digestion and Absorption of Lipid


5

-


5


5

A2

(micelles)

2- + 2 FFA

+ FFA

+ FFA


5

10,000N


5

(6C10C)(2C4C)(mixed micelles)


5

TG

+ FFA


5

(apo) B48CAA

TGCEPL

+

(chylomicron, CM)

TG

2-

CE

PL


5

CoA

CoA + RCOOH RCOCoA

ATP AMP PPi

CoA

CoA

R2COCoA

CoA

R3COCoA CoA


5


Metabolism of triglyceride

Metabolism of Triglyceride


5


5

  • (triacylglycerol)

  • (simple triacylglycerol);(mixed triacylglycerol)


5


5

1.

1g TG = 38kJ

2.

21%26


5

    • (fat mobilization)FFA


5

  • (hormone-sensitive triglyceride lipase , HSL)

ACTH TSH

E2


5

ATP

+

+

+

G

-

AC

HSLa()

cAMP

PKA

HSLb()

DG

TG

FFA

FFA

FFA

  • HSL-----


5


5

-

,


5

1. CoA

CoA

+

CoA-SH

ATP AMP PPi

CoA(acyl-CoA synthetase)


5

2.CoA-

carnitine acyl transferase -


5

FAD

FADH2

CoA

2-CoA

H2O

2--CoA

NAD+

L(+)-

CoA

NADH+H+

CoA

CoA-SH

3. -CoA

CoA

L(+)-CoA

CoA

CoA+CoA


5

5


5

CoA

FADH2

NADH + H+

3ATP

2ATP

H2O

H2O


5

2ATP

CoA

FAD

FADH2

AMP

PPi

H2O

CoA

ATP

CoASH

H2O

2

--CoA

3ATP

L(+)-

CoA

H2O

NAD+

NADH+H+

CoA-SH

CoA

TAC


5

4.

16

2

-

  • 1CoA

    • 1CoA

    • 1NADH+H+

    • 1FADH2


5

  • 7 8CoA

    • 7NADH+H+

    • 7FADH2

    • ATP810 + 72.5 + 71.5 = 108

  • ATP108 2 = 106


5

ATP


5

3-2CoA

3-CoA

2-CoA

2-CoA

H2O

D(-)-CoA

D(-)-CoA

L(+)-CoA

1.


5

CoA

912

3

CoA

36

3,2-

CoA

CoA

26

2


5

O

H

2

SCoA

1

3

c

H

C

3

O

CoA

2

CoA

D(+)--CoA

-CoA

L(-)--CoA

4

4 CoA


5

2.

(C20C22)

FAD


5

ATP

CO2

5-

3.CoA

Ile Met Thr Val

CH3CH2CO~CoA

L-CoA

D-CoA

CoA

TAC


5

(acetoacetate) -(-hydroxybutyrate)(acetone)(ketone bodies)

  • 0.03~0.5mmol/L(0.3~5mg/dl)


5

CO2

1.

HMGCoA

CoASH

CoA

CoASH

HMGCoA

NADH+H+

NAD+

-


5

2.

CoA

NAD+

NADH+H+

CoA

CoASH+ATP

PPi+AMP

CoASH

CoA

CoA


5

2CoA

CoA

CoA

HMGCoA

CoA

D(-)--

CoA

2CoA


5

3.


5

FFA

4.

1


5

FFATG

CoA

CoA

+

CoA

2

-


5

3CoACoA

CoACoA


5

1.

    • 16


5

CoA

Glc

2.

CoAATPHCO3-NADPHMn2+

  • CoA:

CoA -(citrate pyruvate cycle)

  • NADPH:


5

CO2

CO2

NADP+

H2O

CoA

NADPH+H+

AMP PPi

ATP

ATP

CoA

CoA

CoA


5

ADP+Pi

ATP

- + HCO3

--CO2

--CO2+ CoA

- + CoA

3.

1CoA

  • :

ATP + HCO3- + CoA

CoA+ADP + Pi


5

CoA (acetyl CoA carboxylase)Mn2+


5

2

CoACoA2


5

7CoA---


5

  • 7


5

(ACP)

  • 4-,


5

CE-S-

()

CoA

CoA

ACP-S-


5

NADP+H+

CO2

NADP+

H2O

NADPH+H+

NADP+


5

C

E

A

C

P

A

C

P

C

E

S

S

HS

O=C

HS

C=O

CH2

CH2

CH2

CH2

CH3

CH3

E2--SHACP) E1--SHCE


5

O-

O=C

A

C

P

A

C

P

A

C

P

CH2

4H++4e-

4H++4e-

4H++4e-

CH2

C

E

CO2

CO2

CO2

CH2

S

S

S

CH2

C

E

A

C

P

C=O

C=O

C=O

CH2

CH2COO-

CH2COO-

CH2COO-

C

E

S

CH2

C

E

O=C

S

CH2

CH2

S

O=C

CH2

CH2

C=O

S

CH3

CH2

S

O=C

CH2COO-

CH2

CH2

O=C

CH2

CH2

CH2

C

E

A

C

P

CH2

CH2

CH2

+

CH2

CH2

CH2

CH2

CH3

CH2

CH2

CH3

CH2

HS

HS

CH3

CH3

7


5

  • :

CH3(CH2)14COOH

+

7 CO2

+

6H2O

+

8HSCoA

+

14NADP+

CH3COSCoA

+

7 HOOCH2COSCoA

+

14NADPH+H+


5


5

1.

CoA NADPH+H+2CoASH2418


5

2.

  • CoA NADPH+H+--22426


5

H++NADH

E-FAD

Fe2+

Fe2+

CoA+2H2O

NAD+

E-FADH2

Fe3+

Fe3+

CoA+O2

NADH-cytb5

Cytb5

4589

91215


5


5

1.

  • CoA

    • CoACoA

NADPHCoA


5

CoAATP-

TG

+

+

TG

2.

  • CoA

PKA


5

TGVLDL

CMVLDLFA


5

  • CMFFA


5

CoA

CoA

CoA

CoA

CoA

CoA

R1COCoA

R2COCoA

R3COCoA

Pi


5

ATP

ADP

  • 3-


5

  • (prostaglandin, PG)

  • (thromboxane, TX)

  • (leukotrienes, LT)


5

20:4581114

  • (PG)


5

PG 9


5

R1R2PG123


5

  • (TX)


5

(LTB4)

  • (LT)

  • ,


5

PGTXLT

1.

PG

TX


5

2.

(LTA4)

lipoxygenase

(5-HPETE, 5-hydroperoxy-eicotetraenoic acid)

LTB4LTC4

LTD4LTE4


5

PGTXLT

1. PG

  • PGE2

  • PGE2PGA2

  • PGE2PGI2

  • PGF2


5

2. TX

  • PGF2TXA2 PGI2 PGI3

  • TXA3TXA2


5

3. LT

  • LTC4LTD4LTE4

  • LTD4

  • LTB4


Metabolism of phospholipid

Metabolism of Phospholipid


5


5

FA

FA

Pi

X

FA

Pi

X

X


5


5

X =


5


5


5

(cephalin)

(lecithin)

(phosphatidyl inositol)

(phosphatidyl serine)


5

(cardiolipin)


5

()

1(ceramide)


5

  • (sphingolipids)

    • (sphingosine)


5

X

X


5


5

  • ATPCTP


5

3.

1


5

2CDP-


5

  • S-


5

(phospholipid exchange proteins)16,00030,000pH5.0


5

X

R1R2


5

PLA1

PLB2

PLD

PLB1

PLA2

PLC

(phospholipase , PLA)


5

CoANADPH+H+FADH2


5


5


5

N-

(PLC)


Metabolism of cholesterol

Metabolism of Cholesterol


5


5

  • (cholesterol)


5

(27)


5

(29)

(28)


5

140

    • ,


5

  • D


5

CoANADPH


5

1

18CoA + 36ATP + 16(NADPH+H+)

CoA-


5


5


5

  • HMG-CoA

  • (

  • HMG-COA


5

  • HMG-CoA


5

  • HMG-CoA

  • HMG-CoA


5

(bile acid)


5

D3

7-


5

Metabolism of Lipoprotein


5


5


5


5

CM

(lipoprotein)


5

  • CMVLDLLDLHDL

chylomicron ( CM)

very low density lipoprotein (VLDL)

low density lipoprotein (LDL)

high density lipoprotein (HDL)


5


5

(apolipoprotein, apo)

  • 20

apo A: AAA AV

apo B: B100B48

apo C: CCCC

apo D

apo E


5

AHDL

B100E LDL

ALCAT ()

CLPL ()

ALPL

CLPL

AHL ()


5

TG


5

TG

apo B48A

A A

+


5

FFA

CM

CM

CM

LPL

LDL


5

LPL

  • CMTGFA

  • CM

  • TG


5

TG

+ apo B100E

LPLHL

LPL

VLDL

LDL

VLDL

FFA

FFA

LPL HL


5

VLDL

  • VLDLTG


5

  • VLDL

  • LDL

LDL,apo Eapo B100apo B,E


5

VLDL


5

ACATCoA


5

  • LDL

LDLLDLLDL (ox-LDL)(scavenger receptor, SR)LDL


5

LDL


5

45%LDL2/3LDL1/3

  • LDL


5

CMVLDLapo AAAapo CHDL

HDL1

HDL2

HDL3


5

VLDL LDL

CE

CETP

LCAT

CM VLDL

apoC apoE

CM VLDL

CMVLDL

apoA A

HDL

HDL3

HDL2

LCAT

CETP


5

LCATapo A

HDL23

HDL

HDL


5

HDLSR-B1

  • HDL VLDL

    • HDL


5

HDL


5

  • HDL

  • (reverse cholesterol transport, RCT)

  • HDLapo


5

RCT

HDL(acceptor)ABCA1RCT

HDLCE

,


5

ABCA1

ABCA1ATPAI (ATP-binding cassetle transporter A1)(cholesterol-efflux regulatory protein, CERP)


5

2261

ABCA1

ATP

12(motif)


5


5

(hyperlipoproteinemia)


5

  • ()

  • ()


5

atherosclerosisAS

1. LDLVLDLAS

  • As

  • LDLAS


5

LDL

mmLDL

oxLDL


5

2. HDLAS

HDLAS

1

2LDL


5

LPLLCATapoCBEACLDL


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