What are the lipoproteins and what are they used for in the body

Because lipids are insoluble in water, they cannot circulate freely in the blood. For this reason, they are linked with special proteins (the apolipo-proteins or apoproteins) and form complex substances (the lipoproteins) that are soluble in water and can be transported through the blood circulation all over the body. More specifically, the lipoproteins contain a lipid core (from free cholesterol, cholesterol esters, triglycerides and phospholipids) and a protein cover, the apolipoproteins. Lipoproteins are distinguished into five main categories (Table 23.1), depending on their density: chylomicrons, very low density (VLDL), intermediate density (IDL), low density (LDL) and high density lipoproteins (HDL). There are many apolipoproteins (A-I, A-II, A-IV, B-48, B-100, C-I, C-II, C-III, D, E, apo(a)), which not only participate as structural components in the molecule of the various lipoproteins, but also have very important biologic participation in their metabolism. The lipoprotein Lp(a) is a special form of low-density-lipoprotein (LDL), which is surrounded by a special apolipo-protein, the apo(a). It should also be noticed that the fatty acids can circulate in the serum as free fatty acids (FFAs), bound to albumin.

Table 23.1. Classification of lipoproteins

Lipoproteins

Chylomicrons

VLDL

IDL

LDL

HDL

Subclasses

1, 2, 3

2, 3

Diameter (nm)

500

43

27

27, 26.6, 26

9.5, 6.

Composition (%)

Proteins

2

10

18

25

55

Triglycerides

85

50

26

10

4

Cholesterol

1

7

12

8

2

Cholesterol

esters

3

13

22

37

15

Phospholipids

9

20

22

20

24

Apolipoproteins

B-48, A-I,

B-100,

B-100,

B-100

A-I, A-

A-II, C-I,

A-I, A-II,

B-48,

C-I,

C-II, C-III,

C-I, C-II,

E

C-III

E

C-III, E

D, E

VLDL: Very low density lipoproteins; IDL: Intermediate density lipoproteins; LDL: Low density lipoproteins; HDL: High density lipoproteins

VLDL: Very low density lipoproteins; IDL: Intermediate density lipoproteins; LDL: Low density lipoproteins; HDL: High density lipoproteins

Epidemiological studies have shown that an increase in the level of total cholesterol (TC) and of low-density-lipoprotein cholesterol (LDL-C) is associated with an increased risk for cardiovascular events. The level of high-density-lipoprotein cholesterol (HDL-C), however, is associated with low risk, both in the general population and in diabetic patients. The lipoprotein Lp(a) level has also been associated with elevated risk for such events.

How are the lipids and lipoproteins metabolized in the body?

The metabolism of lipids and lipoproteins can generally be divided into two overlapping metabolic pathways, the exogenous and the endogenous (Figure 23.1).

Endogenous Lipoprotein Metabolism

Figure 23.1. Endogenous and exogenous lipid metabolism pathway. LPL = Lipoprotein Lipase, HL = Hepatic Lipase, CETP = Cholesterol Ester Transfer Protein, LCAT = Lecithin Cholesterol Acyltransferase, VLDL = Very low density lipoproteins, IDL = Intermediate density lipoproteins, LDL = Low density lipoproteins, HDl = High density lipoproteins, FFA = Free fatty acids, apoB = apolipoprotein B (Reprinted from Textbook of Diabetes, 3rd edn., J. Pickup & G. Williams, Copyright 2003, with permission from Blackwell Science Ltd.).

Figure 23.1. Endogenous and exogenous lipid metabolism pathway. LPL = Lipoprotein Lipase, HL = Hepatic Lipase, CETP = Cholesterol Ester Transfer Protein, LCAT = Lecithin Cholesterol Acyltransferase, VLDL = Very low density lipoproteins, IDL = Intermediate density lipoproteins, LDL = Low density lipoproteins, HDl = High density lipoproteins, FFA = Free fatty acids, apoB = apolipoprotein B (Reprinted from Textbook of Diabetes, 3rd edn., J. Pickup & G. Williams, Copyright 2003, with permission from Blackwell Science Ltd.).

In the exogenous pathway, the dietary lipids (mainly triglycerides and less so cholesterol), but also the cholesterol emanating from the bile, are absorbed by the intestine in the form of chylomicrons (the main protein component of which is the apolipoprotein B-48). These enter the systemic circulation via the lymphatics and undergo the hydrolytic effect of lipoprotein lipase (LPL), an enzyme found in capillary endothelium (the activity of LPL is increased by insulin and is decreased by apolipoprotein C-III). The FFAs that are released from the chylomicrons are transported in the tissues for storage (as triglycerides in the adipose tissue) or for energy production in the muscles, depending on the needs of the body at that point in time. During the chylomicron hydrolysis, many of their surface components (mainly apolipoproteins) are extracted and transported for the formation of HDL lipoproteins. The residual chylomicron remnants that remain after the hydrolysis of triglycerides are removed by the liver through special receptors. It should be noticed that these remnants are particularly atherogenic, because of their small size and because they are relatively rich in cholesterol. The so-called postprandial lipaemia, attributed to the increase of the chylomicrons and their remnants, constitutes a physiologic phenomenon, which is particularly evident, however, in poorly controlled diabetic patients, as well as when insulin resistance is present (since LPL activity is under the influence of insulin, in insulin resistant situations the hydrolysis of chylomicrons is deficient). Inside the liver cells, chylomicron remnants (that still contain cholesterol) undergo a chain of reactions that 'reassemble' their constitutive lipids into other types of lipoproteins (VLDL) or excrete the cholesterol in the bile.

The endogenous pathway begins with the formation of VLDL lipoproteins in the liver. The liver produces both cholesterol and triglycerides, which 'are packed' together with proteins and phospholipids in large lipoprotein-molecules (VLDL1) and released in the circulation (their main protein component is now the apolipoprotein B-100). Due to the effect of LPL, these large VLDL1 molecules expel triglycerides, take on other apolipoproteins and convert into smaller molecules (VLDL2). Then, with the effect of hepatic lipase [HL], they are converted into still smaller molecules, the IDL-lipoproteins, from which finally the LDL-lipoproteins are formed. These are removed from the circulation via special hepatic LDL-receptors (apo B/E receptors). The cholesterol of these LDL molecules is ultimately removed through the intestine (as free cholesterol in the bile or with the bile acids) or is used by the liver cells for their needs.

LDL receptors exist also on all body cells, serving the purpose of taking up cholesterol from the blood and using it for their needs (steroidogenesis, cell membrane synthesis, etc.). In the event that the clearance of LDL by the liver is deficient for various reasons (lack or reduced number of receptors, disturbance in binding with the receptor, etc.), the LDL molecules remain for a long time in the blood, undergo oxidative modification and become atherogenic (they are taken up by macrophages of the vessel wall, which are converted into foam cells - the precocious cells of the atheromatous plaque). During the process of food-derived chylomicron catabolism and the liver-derived VLDL catabolism (i.e., catabolism of the triglycerides containing lipoproteins), many of their surface components are degraded and are transported into small 'nascent' HDL particles, which are initially deprived from cholesterol and cholesterol esters (they contain apolipoproteins A-I and A-II and phospholipids) and can take up cholesterol from the tissues (HDL3). This cholesterol is subsequently esterified under the effect of a special enzyme (LCAT - Lecithin Cholesterol Acyl Transferase). These mature, larger molecules (HDL2) can then transfer cholesterol outside of the body (either through special scavenger receptors [SR-B1 receptors] in the liver and the kidneys, or through an exchange of cholesterol esters with triglycerides between the HDL and the apo-B containing lipoproteins [VLDL, IDL, LDL], with the effect of the enzyme CETP [Cholesterol Ester Transfer Protein]). The HDL lipoprotein is therefore useful for the 'reverse cholesterol transport' from the tissues to the liver and then outside the body. The more efficient the catabolism of the triglycerides' enriched lipoproteins (for example, due to increased activity of the LPL), the higher the concentration of HDL-cholesterol will be.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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  • MARKUS
    What are lipoproteins?
    7 years ago

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