Lipid Transport Lecture 4 PDF

Lipid transport Professor Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  Lipid transport & storage Lipids: Are insoluble in water so, they are associated with proteins to form the water soluble compounds called lipoproteins. The protein part of l...

Lipid transport Professor Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  Lipid transport & storage Lipids: Are insoluble in water so, they are associated with proteins to form the water soluble compounds called lipoproteins. The protein part of lipoproteins is called apolipoprotein. Lipoproteins are responsible for lipid transport between various tissues. The total plasma lipid is 400 – 600 mg/dl and includes: Triacylglycerol (TAG; 20%), phospholipids (PLs; 30%), cholesterol (C; 40%) and unesterified free fatty acids. The typical lipoprotein consists of:- Lipid part consisting of nonpolar core of TAG and cholesterol ester and Surface layer of PLs and cholesterol. Protein part called apolipoproteins or apoproteins (Apo.) It ranges from 1% in chylomicrons to 60% in some HDLs. Some are peripheral and the others are integral proteins.  Classification of lipoproteins The density of a lipoprotein increases as the protein part increases. Lipoproteins can be separated by 2 methods: ultracentrifugation and electrophoresis into: – Chylomicrons – Very low density lipoproteins (VLDL or pre-β-lipoprotein) – Intermediate-density lipoproteins (IDL) – Low-density lipoproteins (LDL or β-lipoprotein) – High-density lipoproteins (HDL or α-lipoprotein): Lipoprotein (a) [Lpa]: is synthesized in the liver and has the same lipid composition as LDL. It competes with plasminogen to tissue plasminogen receptors. The lipids present in lipoproteins include: Triacylglycerol (TAG), phospholipids (PL), cholesterol, cholesterol esters and free fatty acids (FFAs). TAG is the predominant lipid in chylomicrons and VLDL whereas cholesterol is the predominant lipid in LDL and phospholipids in HDL.  Apo-lipoproteins or apoproteins: Definition: - It is the protein part of lipoproteins. synthesized mainly in liver and small intestine. Types: - 5 major classes from A to E are known: - Apo B: Is present in plasma in 2 forms, apo B100 and apo B48. Apo B100 is the protein component of LDL. Apo B48 (the terminal half of apo B100) is only found in chylomicrons. Apo (a): Is present in LP (a) with apo B100. It has high carbohydrate content. Functions of apolipoproteins – They promote the solubility of lipids in plasma and enhance the stability of the lipoprotein particles. – Act as legends for interaction with lipoprotein receptors in tissues helping to regulate tissue uptake; Apo B-100 and apo E for the LDL receptor. Apo E for remnant receptor. Apo A-I for the HDL receptor.  Some apolipoproteins act as They are enzyme activators Or enzyme inhibitors 1. C-II for lipoprotein lipase, 1. ApoA-II and apoC-III for lipoprotein lipase, 2. A-I for lecithin: cholesterol acyltransferase (LCAT) 2. apo C-I for cholesteryl ester transfere protein.  Metabolism of Chylomicrons Site of synthesis:- intestinal mucosa Function:- Transport of dietary lipids from the intestine to the peripheral tissues Structure:- – Lipids (98%):- mainly triacylglycerol – Proteins:- 1-2%, include apo B-48, apo E and apo C-II Half life: - About 1 hour.  Metabolism of very low-density lipoproteins (VLDL) Site of synthesis:- liver Function:- Transport of endogenously synthesized lipids from the liver to the peripheral tissues Structure:- – Lipids mainly triacylglycerol – Proteins: 10% include apo B-100 apo E and apo C-II Half life: - 1 – 3 hours.  Formation of IDL The action of LpL results in loss of 70-90% of TAG and loss of apo C but not apo E, leading to formation of VLDL remnants, also called intermediate density lipoproteins (IDL). IDL contains less of TAG and more of cholesterol. IDL is either: – Taken up by the liver cells via LDL (apo B-100, E) receptors. – Converted to LDL (majority).