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第四章 血浆脂蛋白及其代谢紊乱 Plasma Lipoproteins and Its Metabolic Disorder. 湘南学院医学检验系 临床生化检验教研室. 本章内容概要. 第一节 血浆脂蛋白结构与受体 第二节 脂蛋白代谢 第三节 脂蛋白代谢紊乱 第四节 脂蛋白代谢紊乱与 AS 第五节 血脂、脂蛋白及载脂蛋白测定. 教学目标. [ 掌握 ] 脂蛋白代谢紊乱(高脂血症分型及特征),血浆脂类及脂蛋白测定方法 。 [ 熟悉 ] 血浆脂蛋白的化学和正常代谢,载脂蛋白的结构与功能 。 [ 了解 ] 脂蛋白受体及代谢有关酶 。. - PowerPoint PPT Presentation
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Plasma Lipoproteins and Its Metabolic Disorder
AS
[] [] [] [] 6
951. 2. 3. 4. 5. 6. 51. 2. 3.
(triglyceride, TG)
(free cholesterol,FC)
cholesterol ester, CE)
(TC)
(phospholipid, PL)
(free fatty acid, FFA)
() plasma lipids (glycolipid)
1 +(TGPLFC+CE) (1) HDL>LDL>VLDL>CM CM>VLDL>LDL>HDL (2) (Apo)()
2 ApoPL(PL) (TGCE)PL ApoPLFC Apo
, TGCE PLFFA
HDL LDL VLDL Lp(a) IDL
CM VLDL LDL HDL CM - LP-LP-LP
(ultra centrifugation method)(density-gradient method) Sf (Svedberg floatation rate)
Sf
d(g/ml)
CM
>400
(electrophoresis method)
TGrich LipoproteinChrich Lipoprotein
CM, , CM (), AS
VLDL
LDL,ASASLDL
HDL HDLAS,
() ()
()(apolipoproteinApo) 12 1972AlaupovicApoABCDEFGHJ
apoAapoAapoAapoAapoAapoAapoAHDL
apoBapoB100apoB48apoB100LDLapoB48CM
apoCapoCapoCapoCapoCVLDLapoB100apoC apoD apoEapoE2apoE3apoE4
3 LCATapoAapoAapoCapoALpLapoCapoAapoCHLapoA
apoBapoBELDLapoEapoBEapoELDLLRPapoAHDL
CETPHDLVLDLLDLPTPCMVLDLHDL apoDLCATapoAapoA-apoD-LCAT
() genotype ()(Phenotype)
1
( 1 )ApoAApoBApo(a)
(intron) 3
(exon) 4
( 2) ApoACA112 ApoECC193
2 ( 1 ) ApoA 1 863bp34 658bp ApoAApoA 11
( 2 ) ApoB 2ApoB100 43kb2829 7 572bp39bp
( 3 ) ApoE 1934 ApoE3 ApoE2ApoE3ApoE4 E2/2E3/3()E4/46 E2/3E2/4E3/4 ( 4 ) ApoC ApoCApoC3347bp 3133bp3,4
( 5 ) Apo(a) 6 525kb1918 Apo(a)2634
ApoCIApoA
*A 11q23-qApoAA1 q23-q23ApoAA11ApoA(a)6Apo(a)B2q24-q23ApoBC19q13.2ApoCC19ApoCC11ApoCD 3ApoDE19q13.2ApoEH 17q23-qApoHJ8p21CL
ApoEApoC ApoCII
19q311q2 , , , ApoCApoAApoAApoA
LDLVLDL
LDLLDL receptor 1974 LDL 1LDL 836115kD5
2LDL1 coated pit ;
(2) ApoB100ApoE ApoB-E ApoB48 LDLApoB100LDLLDL ApoB/ELDL
3LDLLDL receptor pathway 1LDLApoB100EVLDL-VLDLLDLLDL-VLDLVLDL-LP CEApoApoEApoCVLDL
2LDL LDL+LDL LDL-LDLcoated vesicles LDLLDLLDL Apo CE FFA+FC TG +FFA
(3) FC Ch HMGCoA ACATCoAFCCE LDLLDLLDL
4 LDLLDL VLDL CM LDLCMCMApoB48LDLApoEApoCLDLCM
VLDL 1 LDL5 2 ApoEVLDL-VLDLApoB100LDL Ch
3 VLDL-VLDL 4 1As 2
scavenger receptor LDL LDL LDL AsLDL-CELDLLDLLDLLDLLDL
1
220 ku,, LDLN-C-inside-out6N-C
2 1LDL LDLLDLox-LDLAs 2
3 LDLox-LDLAs LDL
HDL(RCT) VLDL-IDL-LDLVLDL, IDLLDL,CMChTGCMLP
(CM)
TG TGTG :
CM
()VLDL1.2.TG(50%-70%)ApoB100ChCM3.TG 4.
VLDLHDL IDL
VLDL TGVLDL
() LDL1.VLDL2. Ch(45%-50%)CEHDL(CETP) APOApoB100 3.4. (1) LDL
2 LDLLDLLDLLDL (ox-LDL)(scavenger receptor, SR)LDL* 45%LDL2/3LDL1/3
LDL
LDL
LDL,LDLLDL
()HDL 1. 2. 3. HDLApoEApoC HDLHDL 4.
HDL
HDLHDL3 HDL2 LCAT CETP
Hyperlipoproteinemia Hyperlipidemia TG/TC
:
ApoLP WHOab
()CM 1. 1LPL 2ApoC Apo C() LPL CMTG CMCM CM 2.
3.14CM 2TG 3CM 4CM 5LPLLPLApoC
()IIa1. LDL (1) LDL (2) LDLLDL (3) LDL LDLLDL LDLLDL-Ch AS
2. ASAS3.12 TG34LDL ApoB
() b-LP -LP 1.: ApoB100VLDLLDL 2. baLDL
3. (1 2 TG 3LPPre LP 4 LDL VLDL
() (-VLDL-) 1. ApoE ApoEApoE2E3E4ApoE(VLDL)E2VLDLApoE3/E3VLDLApoE2/E2VLDLVLDL
2.AS3.1 2TG Ch 3-VLDL LPPre LP--VLDL4 IDL (-VLDL)
() (TG VLDL) 1. VLDL/VLDL
2.142 TG Ch 3 Pre 4 VLDL VLDL
3.
() (CM-LP) 1. ApoC LPL CMVLDL TG LPL
2. 203050
3.12TG Ch 3CM 4CM VLDL
() HDL HDLASASHDLHDL 1 HDL-Ch> 2.6mmol/L0.78-2.2mmol/L0.3-0.85g/L
2 (1) CETPCETPHDL-CEHDL, HDL HTGL, HDL, HDL HDL, HDL-ch(3~5) (2)
CETP HTGL HDL HDL-C2.6mmol/LHDL CETPHTGLHDL
HDL
(secondary hyperlipoproteinemia) () , () () ()
VLDLLPLCMVLDLTG TG
ab: LPL,VLDL; HTGL,IDL; LDL,LDL
Cushing VLDLVLDLLDLa b
ApoBVLDLVLDLLDLb LPLVLDL
AS AS HDLAS
ASASLDL-VLDL oxLDLAS HDLAS AS
AS
CMVLDLLPLCMIDLApoE -VLDL(ApoE)-VLDLASAS
LDL LDLLDLLDL,LDL: LDL LDL LDL LDLApoB100LDLLDLAS
LDL-CAS LDLAB: B(LDL)AS,BLDL,LDLLDLCHD LDL(SD-LDL) BLDL
(a)LP-(a)Lipoprotein(a) 1963LDL
TGPLFCCE ApoB100Apo(a)()
LDL
LP(a)As,Apo(a)As
1 2LDL 3 4 5 6 HDLAS
HDLApoAIApoB
HDL: CENCEHFCHDLNCEH FC: NCEH NCEH
ASAS
TCTGHDL-CLDL-C ApoAIApoBLpa TCTGHDL-CLDL-C 4 TCTG
CDC
12h4
() (CEH)(cholesterol oxidaseCOD)4H2O2(POD) H2O24-(4AAP)(PAP)500nm
-4060001-2 C
2.85.2mmolL
112020405070234
21TC - CoA 2TC
() -----GPO-PAP
C
0.55-1.70mmol/L 2.30mmol/L 4.50mmol/LTG
1TG TGCHDTG 2TG
() .
()---LDLVLDLLp(a)HDL(TC)HDL(HDL-C)HDLTGpH4h
HDL-C 0.9mmol/L
:(1)HDL-CHDL-C0.9mmolL(2)HDL-C(3)TGHDL-C4HDL-C5HDL-C6HDL-C
()-----Friedewald
LDL-CTCHDL-CTG2.2(mmolL) FriedewaldLDL-CTCTGHDL-CLDL-C CMTG>4.52mmolL(400mgd1)-FriedewaldLDL-C
LDL-C 2.13.1mmol/L 2.8mmol/L
: LDL(LDL-C)LDLLDL-CTCLDL-CLDL-CLDL-C
AIB ApoAIApoBApoAApoBApoAIApoBApoAIApoB
ApoAI1.00~1.50gLApoB0.80~1.00gL
ApoAIHDLHDLApoBLDLLDLLDLApoAIApoB,HDL-CLDL-CApoAIApoBApoAIApoB
1 2ApoAAB100 C 3LDL??LDL??? 4CM VLDL LDL HDL 5? 6? 7APOA1APOB100HDLLDL
1.063g/ml(1.75mol/L Nacl)1.063 1.063(HDL) Sf LDL VLDLLDL LDL VLDLLDL
1 ApoB100/ApoE,ApoB100ApoELDLligand VLDLVLDL-VLDL2EGF 3 4 5 C- LDL,LDLLDL