LIPIDS AND LIPOPROTEINS

1. LIPIDS AND LIPOPROTEINS BY: DR. A. P. ABOYEJI DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY UNIVERSITY OF ILORIN TEACHING HOSPITAL, ILORIN, KWARA STATE. AT PRIMARY REVISION COURSE AUGUST 2006 OF THE FACULTY OF OBSTETRICS AND GYNAECOLOGY (WACS)

2. LIPIDS AND LIPOPROTEINS LIPIDS: Are heterogeneous group of compound. Are related more by physical than chemical properties. They are: Relatively insoluble in water Soluble in non polar solvents such as ether, chloroform and benzene. Lipid in general have high energy value and they contain fat soluble vitamins and essential fatty acids. BIOMEDICAL IMPORTANCE Serves as efficient source of energy when stored in adipose tissue. Nerve tissue contains high content of fat. Combination of fat and protein (lipoprotein) are important cellular constituent and serves as transporting lipids in the blood. CLASSIFICATION SIMPLE OR COMPLEX SIMPLE LIPIDS: Esters of fatty acids with various alcohol. Fats. Esters of fatty acids with glycerol. Waxes –Ester of fatty acid with higher molecular WT monohydric alcohols. COMPLEX LIPIDS: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid. Phospholipids: Lipids containing in addition to fatty acids and an alcohol a phosphoric acid residue I.e. glycerophospholipids.

3. Glycolipid: Lipids containing a fatty acid sphingosine and carbohydrate. • Other complex lipids include sulpholipids, aminolipid and lipoproteins. • PRECUSORS AND DERIVED LIPIDS: These include fatty acids, glycerol, steroids, lipid-soluble vitamins and hormone. SELECTED LIPID OF SIGNIFICANCE FATTY ACIDS – They are aliphatic carboxylic acids. • Occur mainly as esters in natural fats and oil. • However occur as free fatty acids in unesterified form - a transport form found in plasma. • Those that occur in natural fats are usually straight chain derivatives and contain even number of carbon atoms. • Chain may be saturated (containing no double bonds) or unsaturated (containing one or more double bonds) Can also be divided into • Monounsaturated • Polyunsaturated • Eicosanoids – Are derived from eicosa (20 - carbon) polyenoic fatty acid comprise the prostannoids, leukotrienes (LTD) and lipoxin LXs. • Prostanoid include prostaglandins (PGs) prostacyclins (PGIs), and thromboxanes (TXs). The prostaglandins exist virtually in every mammalian tissues acting as local hormone.

4. The physical and physiologic properties of fatty acids reflect chain length and degree of unsaturation I.e. the melting point of even numbered-carbon fatty acids increase with chain length and decrease according to unsaturation. Triacyglycerols (Triglycerides) are the main storage forms of fatty acids. PHOSPHOLIPIDS The main lipid constituents of membrane. They include: phosphatidic acid phosphatidylglycerol Phosphatidylcholine * Phosphatidylethonolamine Phosphatidylinositol * Phosphatidylserine Plasmalogen * Sphingomyelins They are all phosphoacyglycerols except sphingomyelins Phosphatidylcholines (Lecithine) occur in cell membrane and they are the most abundant phospholpids of cell membrane and a large proportion of body’s store of choline. Choline is important in nervous transmission as acetycholine and a major constituent of the surfactant preventing adherence due to surface tension of the inner surface of the lung. It’s absence in preterm infant causes respiratory distress syndrome. Lipid peroxidation (auto-oxidation) yield free radical which may cause cancer, inflammatory diseases artherosclerosis and aging. Is a chain reaction providing continous supply of free radical that initiate further peroxidation

5. CHOLESTEROL • Best known steriod • Derived about equally from diet and biosynthesis. • Liver and intestines account for appropriately 10% each. • Virtually all tissues containing nucleated cells are capable of synthesizing cholesterol. • Essential component of membrane and outer layer of plasma lipoprotein. • Stored as cholesterol ester in many tissue mediated by LDL. • HDL transport cholesterol from tissue for conversion to bile acids in the liver. • A major constituent of gallstones • A precusor of important steriods – adenocortical hormone, sex hormones, D vitamins and cardiac glycosides. • Associated with artheroselerosis. • It is excreted in the bile as cholesterol or bile acids salts • Primary bile acids (cholic acid and chenodeoxy cholic acid) are synthesized from cholesterol. Enter the bile as conjugated. • In the intestine some 10 bile acids are deconjugated to secondary bile acids (deoxycholic and lithocholic) • About 98 – 99% of the bile acids are returned to the liver by absorption in the ileum (enterohepatic circulation). • Diet rich in polyunsaturated and monounsaturated fat lower plasma cholesterol while diet rich in saturated fat increase it. • Exercise lower cholesterol • Free fatty acids lead to inc. VLDL in the liver and about inc .Cholesterol can be brought by emotional stress, Cigarette smoking, Coffee drinking and large meals. • Inherited disorder of lipoprotein metabolism may lead to either hypo or hyperlipoproteinimia.

6. LIPOPROTEIN Combination of lipids and proteins to effect transportation of lipid in aquous environment. Transfer lipids as chylomicrons from intestine and from the liver as very low density lipoproteins (VLDL) to most tissues for oxidation and to adipose tissue for storage. 4 major classes of lipids are present in lipoprotein, triacyglycerols, phospholipids, cholesterol and cholestery esters. . 4 major groups of lipoprotein Chylomicrons from intestinal absorption of triacyglycerol Very low density lipoproteins (VLDL or pre -lipoproteins) derived from liver to export triacyglycerol. Low density lipoprotein (LDL, or -lipoproteins) a final stage in the cartabolism of VLDL. High density lipoproteins (HDL or -lipoprotein) involved in VLDL and chylomicron metabolism and cholesterol transport. Also derived from liver and intestine. Tryacyglycerol is the predominant lipid in chylomicrons and VLDL. While cholesterol and phospholipid are the predominant lipids in LDL and HDL.

7. COMPOSITION/STRUCTURE A typical lipoprotein I.e. VLDL consist of Lipid core mainly of non polar triacyglycerol and cholesteryl ester. A single surface layer of amphipathic phospholipid and cholesterol molecules. Protein moiety known as apolipoprotein or apoprotein. Some of the apolipotroteins are integral and cannot be removed whereas other are free to transfer to other lipoproteins. The distribution of the apolipoprotein characterizes the lipoprotein. REGULATION OF METABOLISM Chylomicrons and VLDL are rapidly catabolized by lipoprotein lipase in adipose tissue, heart, muscles and liver. Chylomicron loses about 90% of the triacyglcerol resulting in chylomicron remnant. The liver is responsible for uptake of the remnant. Similar changes occur VLDL resulting in the formation of VLDL remnants or IDL (Intermediate Density lipoprotein) which is finally converted to LDL. LDL is metabolized via LDL receptor and is not rapidly catabolized as VLDL. HDL is synthesized both from the intestine and liver and takes part in both lipoprotein, triacyclycerol and cholesterol metabolism. Newly secreted, (Nascent) HDL from intestine does not contain apo C or E but only apo A. Thus apo C and apo E are synthesized in liver and transferred to intestinal HDL. A major function of HDL is therefore to act as repository for apo C and apo A required in the metabolism of chylomicron and VLDL. HDL removes cholesterol from tissues to liver. In the liver hepatic lipase release the HDL which reenters the cycle- (Reverse cholesterol transfer). HDL Conc. Vary reciprocally with plasma triacyglycerol conc. And directly with activity of lipoprotein lipase.

8. Lipase activity is increased by androgens and decreased by estrogens. • The liver plays a central role in the metabolism of lipoprotein particularly VLDL. • Factors that enhance the synthesis of triacyclycerol and therefore secretion of VLDL include: • Well fed state. • High carbohydrate diets • High levels of circulating free fatty acids • Insulin. • HORMONES THAT REGULATE FAT METABOLISM • Insulin reduces free fatty acid release • By enhancing lipogenesis. Oxidation of glucose to Co2 and • Inhibiting the activity of hormone-sensitive lipase. • While • Epinephrine • Nor Ephinephrine • Glucagon • ACTH, MSH, TSH, GH, and vasopresin increase free fatty acid release from adipose tissue. They act in a facilitatory capacity.