LIPOPROTEIN METABOLISM

Lipoprotein Metabolism

ENZYMES, RESEPTORS, ANTIOXIDANTS AND LIPID

ENZYMES, RESEPTORS, ANTIOXIDANTS AND LIPIDS

Enzymes

Lipoprotein lipase (LPL), found in muscle and adipose tissue capillaries, hydrolyses lipoprotein triglycerides. Hepatic lipase also hydrolyses lipoprotein triglyceride and is involved in the conversion of IDL to LDL. Cholesterol synthesis is controlled by 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase). Non-hepatic cells receive most of their cholesterol from LDL not from endogenous synthesis. A fall in cell cholesterol up regulates HMG-CoA reductase. A great deal of the lipoprotein-cholesterol that is secreted subsequently returns to the liver, either on LDL or from reverse transport on HDL.

Lecithin cholesterol acyltransferase (LCAT), which accompanies HDL, esterifies free cholesterol, the ester moving to the HDL core. HDL3 becomes the larger HDL2; this process may be reversed by hepatic lipase. LCAT aids the removal of phospholipids and free cholesterol from VLDL during catabolism, and also their passage to HDL.

Lipids exchange between lipoproteins and there is active enzyme-mediated transfer. Cholesterol ester transfer proteins (CETP) pass HDL cholesterol ester to VLDL with reverse movement of triglycerides: this limits the accumulation of cholesterol ester in HDL, However, excess cholesterol ester in VLDL may not be physiologically appropriate.

Receptors

Lipoproteins are recognizes apoB100, and IDL apoE, taking up cholesterol into the cell. Higher cholesterol levels in the cell lead to :
1. Increased acyl cholesterol acyltransferase (ACAT) activity with cholesterol re-esterification.
2. Inhibition of HMG-CoA reductase and cholesterol synthesis.
3. Decreased new LDL-receptor synthesis and membrane insertion.
LRP binds multiple apoE copies on chylomicron remnants, facilitating their hepatic removal.

Atherosclerotic plaques are an inflammatory response to vessel wall injury; they contain macrophages and T lymphocytes, and have cytokine and growth factor expression. Endothelium modifies LDL, with phospholipid peroxidation and apoB degradation.

Activated macrophage with acetyl-LDL or oxidized-LDL receptors avidly remove modified LDL. Macrophage uptake may be a helpful scavenging mechanism, but in excess macrophage become lipid-laden foam cells of the fatty streak, which have a pivotal role in atherogenesis.

Antioxidants

Antioxidants may protect LDL from oxidative damage, and may be anti-atherogenic. The antioxidants vitamin E and β-carotene are carried on LDL. Changes in diabetic metabolism that predispose to lipoprotein oxidation may accelerate atherogenesis.


See images as description on the links below :
1.Lipid (cholesterol); transport, penetration, and balance
2.Forming of The Mixed micelle
3.Helical wheel projection of a portion of ApoA-I

STRUCTURE AND FUNCTIONS OF LIPOPROTEINS

STRUCTURE AND FUNCTIONS OF LIPOPROTEINS


Lipids are transported in blood as large macromolecules; these are complexes with proteins. Free fatty acids are the exception, mainly binding to albumin. Hydrophobic lipids, triglycerides and phospholipids are within the lipoprotein core, with the polar portions of phospholipids and the water-soluble alcohol portion of free cholesterol projecting into the aqueous environment, causing solubilization of the lipoprotein.

Types of lipoproteins are chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), Low-density lipoprotein (LDL) and High-density lipoprotein (HDL). Lipoprotein classes can be separated physicochemically, either by electrophoresis wich uses surface charge or by ultracentrifugation which uses relative density.


Chylomicrons are the largest, lightest lipoproteins, they carry dietary triglycerides to be hydrolysed by peripheral tissues lipoprotein lipase (LPL). Fatty acids either provide energy or are stored as triglycerides. Whereas VLDL carry triglycerides synthesized in the liver also to the periphery. LDL are the main cholesterol carriers, delivering cholesterol to peripheral tissues, or back to the liver, through LDL receptors. IDL normally undergo rapid conversion to LDL or are removed by the liver.

As triglycerides are removed, chylomicrons and VLDL shrink in size, and are further catabolized as remnants. Chylomicron remnants are removed by a liver chylomicron remnant receptor, known as LRP (LDL receptor-related protein) or the α2-macroglobulin receptor, VLDL remnants, intermediate-density lipoproteins (IDL), are acted on by hepatic lipase, removed by the liver or converted to low-density lipoproteins (LDL).

Apolipoproteins

The apoliporoteins are major components of lipoproteins. Apolipoproteins have structural and functional roles; stabilization of the molecule; receptor-recognition peptides for cell lipoprotein uptake; or coenzimes for lipid metabolism. Types of apolipoproreins are apoprotein B (apoB48 and apoB100), apoprotein C (apoC-I, apoC-II and apoC-III; the last has three isoforms: C-III0, C-III1 and C-III2), apoprotein E, apoprotein A (apoA-I, apoAII) and apoprotein (a).

Lipoprotein Structure

Generalized structure of a plasma lipoprotein is shown on the figure below.


The similarities with the structure of the plasma membrane are to be noted. A small amount of cholesterol ester are triacylglycerol are to be found in the surface layer and little free cholesterol in the core.

BIOSYNTHESIS SUMMARY OF CHOLESTEROL

Biosynthesis Summary of Cholesterol

STEROIDS CHEMICAL STRUCTURE

LIPIDS -- Steroids Chemical Structure

PHOSPHOLIPID AND BIOLOGICAL MEMBRANE STUCTURE

Phospholipid Bilayer and Biological Membrane
Sructure

LIPIDS (FAT AND PHOSPHOLIPID) STUCTURE

Fats and Phospholipids

A

B

C

D

E


A. Fat Structure, B. Glycerol, C. Saturated Vs Unsaturated, D. Phospholipid Stucture, E. Phospholipid Bilayer

LIPIDS TEST AND YOUR LIPIDS PROFILE MEAN

LIPIDS TEST AND YOUR LIPIDS PROFILE MEAN


This blood test measures the level of fats (lipids) in your blood. It is best to have a blood test called a “lipids profile” or a “lipoprotein profile” to find out your cholesterol and triglyceride numbers. After you eat, your body digests the fat in your food and releases it into your bloodstream in two forms, cholesterol and triglyceride. For the test , blood is drawn from a vein in your arm and sent to a laboratory where blood fats are measured. To get an accurate reading, it’s best to fast for at least 12 hours before blood is drawn.

People who don’t have diabetes should have a lipids test every 3 to 5 years – more often if their blood fat level are above normal or they have a family history of elevated blood fats. People with diabetes should have the test at least once a year. That’s because diabetes can accelerate the development of clogged and hardened arteries (atherosclerosis), which increased your risk of a heart attack, stroke and poor circulation in your feet and legs.

This blood test gives information about your total cholesterol level, LDL (bad) cholesterol level – the main source of cholesterol buildup and blockage in the arteries, HDL (good) cholesterol level– helps keep cholesterol from building up in the arteries, Triglycerides level – another form of fat in your blood. If it is not possible to get a lipid profile done, knowing your total cholesterol and HDL cholesterol can give you a general idea about your cholesterol levels. If your total cholesterol is 200 mg/dL or more or if your HDL is less than 40 mg/dL, you will need to have a lipid profile done.

See how your cholesterol and triglyceride numbers compare to the values below, according to The National Cholesterol Education, a branch of The National Institutes of Health. Cholesterol and triglyceride levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood.

Total Cholesterol level :
Lower than 200 mg/dL, your level mean is desirable
200 mg/dL – 239 mg/dL, your level mean is borderline high
240 mg/dL or higher, your level mean is high

LDL Cholesterol level :
Lower than 100 mg/dL, your level mean is optimal
100 mg/dL – 129 mg/dL, your level mean is near optimal
130 mg/dL – 159 mg/dL, your level mean is borderline high
160 mg/dL – 189 mg/dL, your level mean is high
190 mg/dL or higher, your level mean is very high

HDL Cholesterol level :
Lower than 40 mg/dL, your level mean is low
60 mg/dL or higher, your level mean is high

Triglicerides level :
Lower then 150 mg/dL, your level mean is normal
150 mg/dL – 199 mg/dL, your level mean is borderline high
200 mg/dL – 499 mg/dL, your level mean is high
500 mg/dL or higher, your level mean is very high

HDL (good) cholesterol protects against heart disease, so for HDL, higher numbers are better. A level less than 40 mg/dL is low and is considered a major risk factor because it increases your risk for developing heart disease. HDL levels of 60 mg/dL or more help to lower your risk for heart disease. Triglycerides can also raise heart disease risk. Levels that are borderline high (150-199 mg/dL) or high (200 mg/dL or more) may need treatment in some people. As you compare your numbers with these values, remember that numbers alone don’t tell the whole story. Ask your doctor to interpret your test result.

A rising level of blood fats can alert your doctor to increased risk of blood vessel damage. Knowing your blood fat levels also helps your doctor determine if you could benefit from medication to lower your cholesterol or triglyceride levels. Diet and exercise are the first defenses against unhealthy blood fat levels, just as they are in managing diabetes. A cholesterol or triglyceride lowering medication may be prescribed if these steps aren’t effective or if your LDL or triglyceride levels are extremely high.

By Andi Surya Amal


References :
1. National Cholesterol Education Program, Adult Treatment Panel III,2002
2. Mayo Foundation for Medical Education an research (MFMER); What is a Lipid Test, 2003
3. National Cholesterol Education Program , a branch of The National Institutes of Health; High Blood Cholesterol What you need to know , November 2009
4. Reckless JPD, Diabetes and Lipids, Martin Dunitz Ltd, 1994, 11-18
5. Boh, L.E. 1996. Clinical Clerkship Manual. Applied Threpuetics, Inc. Washington, 5-33, 5-34, 5-36

Links to other articles :
1. What are Lipids ?
2. Clinical Laboratory Test of Lipoprotein Panel
3. My article in Bahasa

WHAT ARE LIPIDS ?

WHAT ARE LIPIDS ?


Lipids are organic molecules, largely insoluble in water, and mainly hydrocarbons of varying structure. Lipids are transported in blood as large macromolecules; these are complexes with proteins. Free fatty acids are the exception, mainly binding to albumin.

Cholesterol
Cholesterol is steroid molecule with hydrocarbon chain. Cholesterol ester with fatty acid is much less water soluble than free cholesterol. Cholesterol is a waxy, fatlike substance. Your body needs cholesterol for making cell walls and insulating your nerves. Your liver also uses in to make bile acids, which help digest your food. It’s when have too much cholesterol – especially too much of certain kind – that trouble may occur.

Cholesterol can’t travel through your bloodstream in its original form. During digestion your body coast cholesterol with protein. Once coated, the package is called a lipoprotein (lip-o PRO-teen), or a fat-filled protein. Cholesterol is packaged in three forms :

1. Low-density lipoprotein (LDL)
This form is often described as “bad” cholesterol. One way to remember this is to think of the first L as meaning “lousy”. If you have too much LDL cholesterol in your blood, your body’s cells become saturated with cholesterol , and the cholesterol is deposited on your artery walls, where it accumulates and hardens. This hard substance, an accumulation of plaques, begins to narrow and harden artery wall , making it more difficult for blood to pass through them. If the flow of blood to your heart is severely diminished or completely interrupted, you’ll have a stroke.

2. High-density lipoprotein (HDL)
Unlike cholesterol, which contains mostly protein. This form of cholesterol, HDL cholesterol contains mostly protein. This form of cholesterol is often described as the “good” cholesterol. Think of the H as standing for “healthy”. HDL cholesterol actually picks up cholesterol deposited on your artery walls and transports it to your liver disposal.

3. Very-low-density lipoprotein (VLDL)
Very-low-density lipoprotein is mainly composed of triglycerides, along with smaller amounts of cholesterol and protein. Elevations in VLDL cholesterol also can to increase your risk heart disease.

Triglycerides
Triglycerides are the chemicals in which most fat exists in your body. Your body converts calories it doesn’t immediately need to triglycerides and transports them to fat cells for storage. Later, hormones regulate the release of triglycerides to meet your energy needs between meals. Just as you need some cholesterol for good health, you need a certain level of triglycerides. But high levels can be unhealthy. Most triglycerides are transported through your bloodstream as very-low-density lipoprotein.