Sunday, October 28, 2012

General structure and classification of lipoproteins


Lipids absorbed from the diet and synthesized by the liver and adipose tissue must be transported between various cells and organs for utilization and storage. Since lipids are insoluble in water, the problem of transportation in the aqueous plasma is solved by associating nonpolar lipids (triacylglycerols and cholesteryl esters) with amphipathic lipids(phospholipids and cholesterol) and proteins to make water-miscible Lipoproteins.
General Structure of Lipo protein
 Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids
The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure-1). These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.
 
Figure-1- showing general structure of lipoprotein
 Classification of Lipoproteins
 Lipoproteins can be classified in three ways-
 1) Based on density
Because fat is less dense than water, the density of a lipoprotein decreases as the proportion of lipid to protein increases.  Lipoproteins with high lipid content will have low density and so float on centrifugation. Those with high protein content sediment easily and have a high density. They are separated by Ultracentrifugation. Depending upon the floatation constant (Sf), Five major groups of lipoproteins have been identified that are important physiologically and in clinical diagnosis. These are
 (i) Chylomicons, derived from intestinal absorption of triacylglycerol and other lipids; Density is generally less than0.95 while the mean diameter lies between 100- 500 nm
 (ii) Very low density lipoproteins(VLDL), derived from the liver for the export of triacylglycerol; density lies between 0.95- 1.006 and the mean diameter lies between 30-80 nm.
 (iii) Intermediate density lipoproteins (IDL) are  derived from the catabolism of VLDL,with a density  ranging intermediate between Very low densityand Low density lipoproteins i.e. ranging between 1.006-1.019 and the meandiameter ranges between 25-50nm.
 (iv)Low-density lipoproteins (LDL), representing a final stage in thecatabolism of VLDL; density lies between 1.019-1.063 and mean diameter lies between 18-28 nm
 (iv) High-density lipoproteins (HDL),involved in cholesterol transport and also in VLDL and chylomicron metabolism. Density ranges between 1.063-1.121 and the mean diameter varies between 5-15 nm. (Table)

Figure- 2-showing the relationship of density and mean diameter of lipoproteins

Triacylglycerol is the predominant lipid in chylomicron and VLDL, whereas cholesterol and phospholipid are the predominant lipids in LDL and HDL, respectively. (Table)
 2) Based on electrophoretic mobilities
Lipoproteins may be separated according to their electrophoretic properties into alpha , beta, pre-beta,and broad beta lipoproteins. The mobility of a  lipoprotein is mainly dependent upon protein content. Those with higher protein content will move faster towards the anode and those with minimum protein content will have minimum mobility.
 HDL are alpha , LDLbeta, VLDL pre-beta, and IDL are broad beta lipoproteins. Free fattyacids and albumin complex although not a lipoprotein is an important lipid fraction in serum and is the fastest moving fraction. Chylomicons remain at the origin since they have more lipid content. VLDL with less protein content than LDL move faster than LDL, this is due to nature of apoprotein present.
Table- showing the composition of lipoproteins. As the lipid content increases, density decreases and size increases, that is why Chylomicons are least dense but biggest in size, while HDL are rich in proteins , hence most dense but smallest in size.
 3)Based on nature of Apo- protein content
 One or more apolipoproteins (proteins or polypeptides) are present in each lipoprotein. The major apolipoproteins of HDL Alpha Lipoproteins) are designated A.The main apolipoprotein of LDL (beta -lipoprotein) is apolipoprotein B(B-100), which is found also in VLDL. Chylomicons contain a truncated form of apo B (B-48) that is synthesized in the intestine, while B-100 is synthesized in the liver. Apo B-100 is one of the longest single polypeptide chains known,having 4536 amino acids and a molecular mass of 550,000 Da. Apo B-48 (48% ofB-100) is formed from the same mRNA as apo B-100 after the introduction of a stop signal by an RNA editing enzyme. Apo C-I, C-II, and C-III are smaller polypeptides (molecular mass 7000–9000 Da) freely transferable between several different lipoproteins. Apo E is found in VLDL, HDL, Chylomicons, andchylomicron remnants; it accounts for 5–10% of total VLDL apolipoproteins in normal subjects.
 Functions of Apoproteins- Apolipoproteins carry out several roles: 
 (1) They can form part of the structure of the lipoprotein, eg, apo B is a structural component of VLDL and Chylomicons
 (2)They are enzyme cofactors, e.g. C-II for lipoprotein lipase, A-I for lecithin: cholesterolacyl transferase (LCAT), 
 (3) They act as enzyme inhibitors, eg, apo A-II and apo C-III for lipoprotein lipase, apo C-I for cholesteryl ester transfer protein;
 (4)They act as ligands for interaction with lipoprotein receptors in tissues, eg,apo B-100 and apo E for the LDL receptor, apo A-I for the HDL receptor. The functions of apo A-IV and apo D, however, are not yet clearly defined, although apo D is believed to be an important factor in human neuro degenerative disorders and acts as cholesteryl ester transfer protein required for the exchange of triglycerides and cholesteryl esters between VLDL,chylomicron remnants and HDL.
 All apoproteins are synthesized mainly in liver but small amounts can be synthesized in almost all organs.



------------------------------------------ Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123 Email:ehab10f@gmail.com,ehababoueladab@yahoo.com ------------------------------------------
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