WordNet

a conjugated protein having a lipid component; the principal means for transporting lipids in the blood

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/09 21:49:30」(JST)

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Lipoprotein structure (chylomicron)

ApoA, ApoB, ApoC, ApoE (apolipoproteins); T (triacylglycerol); C (cholesterol); green (phospholipids)

A lipoprotein is a biochemical assembly that contains both proteins and lipids, bound to the proteins, which allow fats to move through the water inside and outside cells. The proteins serve to emulsify the lipid (otherwise called fat) molecules. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins. Examples include the plasma lipoprotein particles classified under high-density (HDL) and low-density (LDL) lipoproteins, which enable fats to be carried in the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and bacterial lipoproteins.^[1]

Scope[edit source | edit]

Transmembrane lipoproteins[edit source | edit]

The lipids are often an essential part of the complex, even if they seem to have no catalytic activity by themselves. To isolate transmembrane lipoproteins from their associated membranes, detergents are often needed.

Plasma lipoprotein particles[edit source | edit]

The scope of lipoprotein particles is to transport triacylglycerols and cholesterol in the blood between all the tissues of the body. The most common being the liver and the adipocytes of the adipose tissue. Particles are created in the intestinum tenue and the liver, but interestingly not in the adipocytes.

All cells use and rely on fats and cholesterol as building-blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems.

The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol, and apoproteins directed outward. Such characteristics make them soluble in the salt water-based blood pool. Triglyceride-fats and cholesterol esters are carried internally, shielded from the water by the phospholipid monolayer and the apoproteins.

The interaction of the proteins forming the surface of the particles (a) with enzymes in the blood, (b) with each other, and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.

Regarding atheroma development and progression as opposed to regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.^{[citation needed]}

Function[edit source | edit]

The handling of lipoprotein particles in the body is referred to as lipoprotein particle metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through de novo synthesis of triacylglycerols.

The hepatocytes are the main platform for the handling of TGs and cholesterol; the liver can also store certain amounts of glycogen and triacylglycerols. Intriguingly, adipocytes, though being the main storage cells for triacylglycerols, do not produce any kind of lipoprotein particle.

Exogenous pathway[edit source | edit]

Bile emulsifies fats contained in the chyme, then pancreatic lipase cleaves triacylglyceride molecules into two fatty acids and one 2-monoacylglycerol. Enterocytes readily absorb this molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triacylglycerides. Then these lipids (i.e. triacylglycerols, phospholipids, cholesterol, and cholesteryl esters) are assembled with apolipoprotein B-48 into nascent chylomicrons. These particles are then secreted into the lacteals in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream.

In the blood stream, nascent chylomicron particles bump with HDL particles; as a result, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent chylomicron; the chylomicron is now considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes the hydrolysis of triacylglycerol (i.e., glycerol covalently joined to three fatty acids) that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage.

The hydrolyzed chylomicrons are now called chylomicron remnants. The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.

Endogenous pathway[edit source | edit]

The liver is the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the hepatocytes. Hepatocytes are also able to create triacylglycerols via de novo synthesis. And the also produce the bile from cholesterol.

In the hepatocytes, triacylglycerols, cholesterol cholesteryl esters are assembled with apolipoprotein B-100 to form nascent VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.

In the blood stream, nascent VLDL particles bump with HDL particles; as a result, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent VLDL particle; Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature.

Again like chylomicrons, VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate-density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase.

Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low-density lipoproteins (LDL), which contain a relatively high cholesterol content ( ^[2] see native LDL structure at 37°C on YouTube). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 on the LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.

Classification[edit source | edit]

By density[edit source | edit]

Lipoproteins may be classified as follows, listed from larger and less dense to smaller and denser. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of electrophoresis and ultracentrifugation.

Chylomicrons carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and to adipose tissue.
Very-low-density lipoproteins (VLDL) carry (newly synthesised) triglycerides from the liver to adipose tissue.
Intermediate-density lipoproteins (IDL) are intermediate between VLDL and LDL. They are not usually detectable in the blood.
Low-density lipoproteins (LDL) carry cholesterol from the liver to cells of the body. LDLs are sometimes referred to as the "bad cholesterol" lipoprotein.
- large buoyant LDL (lb LDL) particles
- small dense LDL (sd LDL) particles
- Lipoprotein(a) is a lipoprotein particle of a certain phenotype
High-density lipoproteins (HDL) collect cholesterol from the body's tissues, and take it back to the liver. HDLs are sometimes referred to as the "good cholesterol" lipoprotein.

.

Density (g/mL)	Class	Diameter (nm)	% protein	% cholesterol	% phospholipid	% triacylglycerol & cholesterol ester
>1.063	HDL	5–15	33	30	29	4
1.019–1.063	LDL	18–28	25	50	21	8
1.006–1.019	IDL	25–50	18	29	22	31
0.95–1.006	VLDL	30–80	10	22	18	50
<0.95	Chylomicrons	100-1000	<2	8	7	84

^[3]

Alpha and beta[edit source | edit]

It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as Abetalipoproteinemia.

Lipoprotein(a)[edit source | edit]

Lipoprotein(a) – Lp(a), Cardiology diagnostic tests

< 14 mg/dL : Normal

14-19 mg/dL : ?

> 19 mg/dL : High risk

How to lower: aerobic exercise, niacin, aspirin, guggulipid.^[4]

Further information: Lipoprotein(a)

Studies[edit source | edit]

Atherosclerosis is the number one mortality cause in the western hemisphere, and since the 1980s, a lot of studies have been conducted to look for correlations between the incidence of the disease and plasma lipoprotein particle concentrations in the blood. Hypothesis exist for possible causations. Studies showed correlation between atherosclerosis and concentrations of particles. Further studies looked for correlations between nutrition and concentration of the distinguishable lipoprotein particles, e.g. whether the ratio of dietary fat raises or lowers levels of LDL particles. Studies showed that different phenotypes regarding the amount of particles and reaction to diet composition do exist.

References[edit source | edit]

^ mrc-lmb.cam.ac.uk
^ Kumar V, Butcher SJ, Öörni K, Engelhardt P, Heikkonen J, et al. (2011) Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16Å Resolution at Physiological Body Temperature. [1]
^ Biochemistry 2nd Ed. 1995 Garrett & Grisham
^ Beyond Cholesterol, Julius Torelli MD, 2005 ISBN 0-312-34863-0 p.91

External links[edit source | edit]

Database of bacterial lipoproteins at mrc-lmb.cam.ac.uk
Overview and diagram at washington.edu
Lipoprotein research at the Medical University of Vienna
Lipoprotein assembly at wisc.edu
Lipoprotein circulation at purdue.edu
Lipoproteins at the US National Library of Medicine Medical Subject Headings (MeSH)
Proteolipids at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. リポ蛋白の分類、代謝、およびアテローム性動脈硬化症における役割 lipoprotein classification metabolism and role in atherosclerosis
2. 血清脂質およびリポ蛋白の測定 measurement of serum lipids and lipoproteins
3. リポ蛋白aと心血管疾患 lipoprotein a and cardiovascular disease
4. HDL代謝およびHDLコレステロール値異常の患者に対するアプローチ hdl metabolism and approach to the patient with abnormal hdl cholesterol levels
5. リポ蛋白糸球体症 lipoprotein glomerulopathy

English Journal

Novel anti-diabetic effect of SCM-198 via inhibiting the hepatic NF-κB pathway in db/db mice.

Huang H, Xin H, Liu X, Xu Y, Wen D, Zhang Y, Zhu YZ.SourceDepartment of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai Chempartner Co. Ltd, Shanghai 201203, People's Republic of China.
Bioscience reports.Biosci Rep.2012 Apr 1;32(2):185-95.
There are reports of early evidence that suggest the involvement of chronic low-grade inflammation in the pathogenesis of Type 2 diabetes. Thus, substances that have effects in reducing inflammation could be potential drugs for Type 2 diabetes. Leonurine (4-guanidino-n-butyl syringate; SCM-198) is
PMID 21859425

Protective effects of calcium on copper toxicity in Pelteobagrus fulvidraco: Copper accumulation, enzymatic activities, histology.

Chen QL, Luo Z, Zheng JL, Li XD, Liu CX, Zhao YH, Gong Y.SourceFishery College, Huazhong Agricultural University, Wuhan 430070, China.
Ecotoxicology and environmental safety.Ecotoxicol Environ Saf.2012 Feb;76(2):126-34. Epub 2011 Oct 21.
The present study was conducted to determine interactive effects of waterborne co-exposure of copper (Cu) and calcium (Ca) on Cu accumulation, enzymatic activities and histology in yellow catfish Pelteobagrus fulvidraco and test the prediction that Ca could protect against Cu-induced toxicity in the
PMID 22019308

Japanese Journal

Bedside Teaching HDLの多面的効果

蔵野信,木下誠
呼吸と循環 60(11), 1166-1171, 2012-11
NAID 40019466757

Effect of plasma lipids, hypertension and APOE genotype on cognitive decline

Yasuno Fumihiko,Tanimukai Satoshi,Sasaki Megumi,Ikejima Chiaki,Yamashita Fumio,Kodama Chiine,Hidaka Shin,Mizukami Katsuyoshi,Asada Takashi,安野史彦,池嶋千秋,水上勝義,朝田隆
Neurobiology of aging 33(11), 2633-2640, 2012-11
… Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. …
NAID 120004921502

Related Pictures

★リンクテーブル★

リンク元	「リポ蛋白」「コレステロール」
拡張検索	「lipoprotein(a)」「familial hypoalphalipoproteinemia」「familial multiple lipoprotein-type hyperlipidemia」「apolipoprotein A-I」
関連記事	「lipoproteins」

「リポ蛋白」

　　[★]

英: lipoprotein, LP
同: リポ蛋白質、リポタンパク、リポタンパク質、リポプロテイン
関: アポリポ蛋白、脂質異常症、血漿リポタンパク、リポプロテイン(a)

WIL.1595

型

密度
(g/mL)

電気移動度

産生部位

組成

主なアポ蛋白

脂
質

コ
レ

リ
脂

蛋
白

AI

AII

AIV

B48

B100

CI

CII

CIII

E

apo(a)

Chylomicrons

< 0.95

Origin

腸

85

●

●

○

Chylomicron remnants

<1.006

Origin

腸

60

20

●

●

VLDL

<1.006

Pre-β

肝臓

55

20

●

IDL

1.006-1.019

β

VLDL由来

35

25

●

●

LDL

1.019-1.063

β

IDL由来

60

5

●

HDL

1.063-1.210

α

肝臓、腸、血漿

5

20

25

50

●

●

HDL2

1.063-1.125

α

HDL3

1.125-1.210

α

Lp(a)

1.050-1.090

α

肝臓

5

60

●

●

IDLをpre-Bとする文献もある。

WIL TABLE 36-3

リポ蛋白

AI

AII

AIV

AV

B100

B48

CI

CII

CIII

E

apo(a)

D

平均血漿濃度 (mg/dL)

130

40

<1

85

Variable

6

3

12

5

Variable

10

染色体

11

1

11

2

19

11

19

6

3

分子量(kDa)

∼29

∼17 (dimer)

∼45

39

∼513

∼241

∼6.6

8.9

8.8

∼34

∼400-800

∼20

ペプチドの長さ(a.a.)

243

77

376

343

4536

2152

57

79

299

4000-6000

169

主な合成部位

肝臓
小腸

肝臓

小腸

肝臓

小腸

肝臓

肝臓
脳
皮膚
精巣
脾臓

肝臓

肝臓
小腸

主な機能

・HDLの構造蛋白
・LCATのCofactor
・コレステロールの逆転送に重要

・apo-Eの受容体への結合を妨げる
(E-AII複合体形成による)

・細胞からのコレステロールの流出を促進する
・LCATの活性化
・小腸からの脂質分泌を促進

・LPLを介した脂質分解の活性化
・肝でのVLDL合成を妨げる？

・VLDL・LDLの構造蛋白
・LDL受容体のリガンド

・カイロミクロンの構造蛋白

・レムナントの受容体への結合を調節する
・LCATを活性化する

LPLのcofactor

・レムナントの受容体への結合を調節する
・LPLを阻害する

・LDLとレムナント受容体のリガンド
・局所の脂質の再配分
・コレステロール逆転送(apo-EをもったHDL)

血栓形成と線維素溶解を調節する

LCATの活性化？

Functions and interrelationships of different classes of plasma lipoproteins

PNAS 1969 64:1128-1137

リポ蛋白の構成 QB CBT vol.1 p.140

コレステロールが多いのがLDL。トリグリセリドが除去されることでVLD　L→　IDL　→　LDL
HDLは蛋白質が多い。HDLは末梢からコレステロールの逆転送のいわばキャリアーとなる。

参考

1. リポ蛋白・コレステロールの代謝マップ

http://www.jokoh.com/dandi/taisya.gif

「コレステロール」

　　[★]

英: cholesterol
同: コレステリン cholesterin
関: lipoprotein

コレステロールは多くの場合、長鎖脂肪酸のコレステロールエステルとして食品に多く含まれる (SP.739)

分子式

C27H46O = 386.66

吸収

小腸から放出された脂質とコレステロールはアポ蛋白とカイロミクロンを形成する。
カイロミクロンは血液循環に入り、循環中にカイロミクロンレムナント chylomicron remnantとなる。

カイロミクロンに含まれる脂質は、血管内皮に存在するリポ蛋白リパーゼ(LPL)により分解されて脂肪酸を遊離し、コレステロールの比が高いカイロミクロンレムナントとなる。

肝臓はカイロミクロンレムナントを取り込む

生合成

コレステロールは酢酸を原料として合成される。

acetyl-CoA→hydroxymethyl-glutaryl coenzyme A(HMG-CoA)－(HMG-CoA reductase)→mebaronate→･･･→コレステロール

→コレステロールの生合成

体内循環

肝臓は血液循環にVLDLを放出する

血液循環中のVLDLの脂質は、、血管内皮に存在するリポ蛋白リパーゼ(LPL)により分解されて脂肪酸を遊離し、コレステロールの比が高いIDL、LDLとなる。

組織からはコレステロール比型が高いHDLが放出され、そのまま肝臓に取り込まれるか、IDLにコレステロールを渡すことでコレステロールの逆輸送を行っている(内因性の抗動脈硬化作用)。

肝臓は血液循環からHDL, IDL, VDLを受容体を介して取り込む

排泄

肝臓でコレステロールは胆汁酸に変換され、胆汁として排出される

see HBC.236

Lipoprotein	Source	Diameter (nm)	Density (g/mL)	Composition		Main Lipid Components	Apolipoproteins
				Protein	Lipid
				(%)	(%)
Chylomicrons	Intestine	90～100	< 0.95	1～2	98.99	Triacylglycerol	A-I, A-II, A-IV,1 B-48, C-I, C-II, C-III, E
Chylomicron remnants	Chylomicrons	45～150	< 1.006	6～8	92.94	Triacylglycerol, phospholipids, cholesterol	B-48, E
VLDL	Liver (intestine)	30～90	0.95～1.006	7～10	90～93	Triacylglycerol	B-100, C-I, C-II, C-III
IDL	VLDL	25～35	1.006～1.019	11	89	Triacylglycerol, cholesterol	B-100, E
LDL	VLDL	20～25	1.019～1.063	21	79	Cholesterol	B-100
HDL1	Liver, intestine, VLDL, chylomicrons	20～25	1.019.1.063	32	68	Phospholipids, cholesterol	A-I, A-II, A-IV, C-I, C-II, C-III, D,2 E
HDL2		10～20	1.063～1.125	33	67
HDL3		5～10	1.125～1.210	57	43
Preβ-HDL3		< 5	> 1.210				A-I
Albumin/free fatty	Adipose acids tissue		> 1.281	99	1	Free fatty acids