Lipoprotein Metabolism

Lipoprotein Metabolism

Basic definitions and terms:

- Lipoproteins: complex compounds formed of lipids bound to proteins to facilitate the transfer of lipids between different tissues.

- Apoproptein: (also called apolipoprotein) the protein ingredient of lipoproteins.

- Integral protein: it is an essential component protein which is penetrating through the whole thickness of the phospholipid layer of lipoprotein particle. Examples: apoA, apoB100 and apoB48.

- Peripheral protein: surface protein component of the lipoprotein which can be exchanged between different types of lipoproteins and act as enzyme activator or receptor binding site.

- Centrifugal transport: transport of lipids from liver to the peripheral tissues, e.g. adipose tissue and muscles.

- Centripetal transport: transport of lipids from peripheral tissues to the liver.

Chylimicrons:

• Synthesis: in the epithelial cells of the small intestines (enterocytes)

- The lipid component is synthesized from the absorbed dietary fatty acids, monoacyl glycerol and cholesterol.

- The apolipoprotein part (apoB48 and apoA) is synthesized in the rough endoplasmic reticulum by the ribosomes.

- The assembly of lipids with apolipoproteins takes place in the Glogi apparatus then they are packed into secretory vesicles where they are secreted by exocytosis into the intercellular space.

- The chylimicrons in this form are called nascent and are drained into the lacteals. They reach the thoracic duct and enter the venous circulation where they receive apoC and apoE from HDL to become mature chylimicrons.

• Structure: mature chylimicrons are about 1µ in diameter and consist of 2% proteins (apoB48, apoA. apoC and apoE) and 98% lipids (mainly triglycerides).
• Fate: the mature chylimicrons reach the peripheral tissues (adipose tissue and skeletal and cardiac muscles) where they are acted upon by the enzyme plasma lipoprotein lipase (LPL) which needs apoCII for its activation. This enzyme is present anchored with heparin sulfate to the capillary endothelium of the fore mentioned tissues. The action of this enzyme results in hydrolysis of triglycerides into glycerol and free fatty acids. The fatty acids are taken up by the cells in these tissues and are either used in the production of energy (skeletal and cardiac muscles) or used in the synthesis of tissue or milk fat (adipose tissues and lactating mammary glands. After losing the main bulk of its triglycerides, the chylimicrons returns the apoA and apoC back to the HDL and become chylimicron remnants. These particles give most of the remaining triglycerides to the HDL in exchange for cholesterol esters by means of CETP (cholestryl ester exchange protein also known as apoD). Then they are recognized by the liver through their apoE component and become endocytosed by the liver cells where they are hydrolyzed into amino acids, cholesterol and fatty acids.
• Function: transport of the absorbed dietary (exogenous) triglycerides to the tissues. They also transport dietary cholesterol and fat soluble vitamins to the liver.

N.B's:

- Plasma lipoprotein lipase is called clearing factor because it clears the plasma from its turbidity caused by the presence of chylimicrons.

- Plasma lipoprotein lipase is activated by insulin and heparin.

- The chylimicrons are called so because they are 1µ in diameter and present in lymph (chyle).

- ApoB48 is encoded by the same gene for apoB100 with the addition of termination code to the mRNA by RNA editing enzymes. It has 48% of the molecular weight of apoB100.

- The neonatal liver has the enzyme LPL.

- Normally chylimicrons can not be detected in the plasma in the fasting state (>12 hours after meals).

Very low density lipoproteins (VLDL):

• Synthesis: in the liver cells (hepatocytes)

- The triglyceride component is synthesized de novo or by re-esterification of free fatty acids.

- The apolipoprotein (apoB100) is synthesized in the microsomes.

- The VLDL in this form is called nascent and is secreted into the sinusoids. They venous circulation where they receive apoC and apoE from HDL to become mature VLDL.

• Structure: VLDL consists of 10% proteins (apoB100, apoC and apoE) and 90% lipids (mainly triglycerides).
• Fate: the mature VLDL reaches the peripheral tissues (adipose tissue and skeletal and cardiac muscles) where it is acted upon by the enzyme plasma lipoprotein lipase (LPL) which needs apoCII for its activation. The action of this enzyme results in hydrolysis of triglycerides into glycerol and free fatty acids. The fatty acids are taken up by the cells in these tissues and are either used in the production of energy (skeletal and cardiac muscles) or used in the synthesis of tissue or milk fat (adipose tissues and lactating mammary glands. After losing the main bulk of its triglycerides, the VLDL returns the apoC back to the HDL and become VLDL remnants (IDL). These particles give most of the remaining triglycerides to the HDL in exchange for cholesterol esters by means of CETP (cholestryl ester exchange protein also known as apoD). Then VLDL remnants give their apoE back to the HDL and become LDL.
• Function: centrifugal transport or the endogenous triglycerides.

Low density lipoproteins (LDL):

• Synthesis: LDL is formed of IDL (VLDL remnants) after exchange of triglycerides for cholesterol ester with HDL and loss of apoE.
• Structure: LDL consists of 20% proteins (apoB100) and 80% lipids (mainly cholesterol).
• Fate: the LDL binds to specific LDL receptors in the liver and peripheral tissues, then it is uptaken and hydrolyzed to give cholesterol.
• Function: important source of cholesterol for peripheral tissues.

High density lipoproteins (HDL):

• Synthesis: HDL is synthesized in the cells of liver and small intestine as discoidal HDL.
• Structure: HDL consists of 32-55% proteins (apoA, apoC, apoE and apoD) and 45-68% lipids (phospholipids and cholesterol).
• Fate: the HDL receives free cholesterol from tissues. This cholesterol may get esterified with fatty acids by means of LCAT (licethine cholesterol acyl transferase). The cholesterol esters are stored between the phospholipid bilayer transforming discoidal HDL to spheroidal HDL. Later on cholesterol esters may be given to chylimicron remnants or VLDL remnants in exchange for triglycerides by means of apoD (CETP cholesterol ester transfer protein).
• Function: - centripetal transport of cholesterol (reverse cholesterol transport pathway).

- reservoir for apoE and apoC needed for maturation of chylimicrons and VLDL.