BIOCHEMISTRY LIPIDBYDr. Basil O M Saleh 23-10-2012, 2nd Class college of Medicine , Baghdad Univ.
1.Introduction2.Cholesterol: Synthesis & Regulation Functions, Correlation with CAD3.Lipoproteins: Definition, Metabolism &DisordersFatty Acids: Biosynthesis, Oxidations & Disorders4.Ketone bodies: Biosynthesis,Regulation& Ketoacidosis5.Triglycerides and phospholipids: Biosynthesis, Functions & Hormonal regulation6.Sphinogolipids, Glycolipids and Sphingolipidosis7.Prostaglandins: Biosynthesis and Functions8. Others
INTRODUCTION Lipids are heterogeneous group of water-insoluble(hydrophobic) organic molecules. Because of their aqueous insolubility, body lipids are generally found compartmentalized(not as free lipids in blood or other body fluids) as1.Memebrane-associated lipids; phospholipids, free cholesterol, sphingolipids2.Droplets in adipocytes as TGs3.Transported in blood as lipoproteins(LPs) such as VLDL, LDL…, or in association with protein , mainly albumin as with fatty acids.
FAs are also classified depending on the degree of saturation into : 1. Saturated (no double bond C=C) 2. Monounsaturated (one C=C), 3. polyunsaturated(PUFA) (2 or more C=C). Naturally occurring FAs are cis form, which acquired them the bend or kink property that is important in the biological membrane structures. This property of bend (kink)increases the fluidity(permeability) of membranes for lipid soluble substances. Trans form has no bend property.
• Unsaturated hydrocarbon
• tails with kinks• Saturated hydro-
• carbon tails
Lipid are classified into1.Simple lipids (Fats & Waxes) 2.Compound or conjugated lipids3.Derived Lipids4.Lipid-associating substances1. Simple lipid: The neutral fat which is an important class of lipids and imply the Triglyceride which contain three FA molecules attached to one molecule of glycerol alcohol by ester bonds. The FAs are usually different. TGs containing saturated FAs tend to be solid at room T and do not have kinks in their structure, while those containing unsaturated cis FAs forms oil at room T and have kinks property. Most TGs from plant sources; corn, sunflower seeds, and safflower seeds are rich in PUFA, whereas TGs from animal sources contain mostly saturated FAs.
(Triacylglycerol):CH2OCOR1 ester bonds or(Triglyceride) CHOCOR2 CH2OCOR3Usually R1 &R3 usually saturated, while R2 unsaturated.Glycerol+R1= MonoacylglycerolGlycerol+R1+R2+DiacylglycrolGlycerol+|R1+R2+R3= Triacylglycerol
2. Compound( Complex) lipids a. PHOSPHOLIPIDS b. Glycolipids c.LipoproteinsPhospholipids They are •The foremost structural components of membranes•Serves as emulsifying agents and surface active agents•They are amphipathic molecules–They are of two types : 1.Phosphoglycerides and 2. Sphingolipids.
CH2OCOR1 Phosphoglycerolipids:
CHOCOR2 glycerol alcohol+ 2FAs+ N-baseCH2OPO3-b
b: is Nitrogen base
Lecithin PL is:1. The predominant type of PL inCM2. The source of choline componentof the neurotransmitter; theAcetylcholine3. The principal lipid component ofLung surfactant(90 % lipid and 10% protein), itsdeficiency in preterm infants is associated with inadequateproduction or secretion ofsurfactant causes RespiratoryDistress Syndrome(RDS), thesignificant cause of death in Infants.
Lecithin is made and secreted bypneumocytes to act as surfactant,decrease the surface tension offluid lining the alveoli so reducingthe pressure needed to reinflate alveoli, thereby preventing alveolarcollapse(atelectasis)4. involved in emulsification of fatdiet in small Intestine along withBile salt. Cardiolipin PL is theprincipal type of PL that involved ininner mitochondrialmembrane structure(important formaintenance of certain respiratorycomplexes).
Anti-cardiolipin ACL & Antiphospholipid APL are used ininvestigation of autoimmune diseases such as in abortion or deadinfant delivery. Platelet activating factorPAF and Plasmalogene Are compounds that belong to PLstructure but differ in containingether linkage ROR instead of esterlinkage ROCOR at C1 of PL. CH2OR1 ether link CHOCOR2 CH2OPOBase
SPHINGOLIPIDS. They are PLs, but it consist of sphingosine alcohol (C18 monoalchol amine)instead of glycerolsphingosine+ Fatty acid= ceramideceramide+NitrogenBase(e.g;choline)= Sphingolipids such as Sphingomyelin. It is an important component of myelin sheath of nerve fibers,insulates and protects neuronalfibers of the central nervoussystem(preventing the shortcirculation of nerve electrical pulsetransmission).
Ceramide+ CHO= glycolipids These are another type of lipid. of which : The simple forms areGlucosylsphingolipid andGalactosylsphingolipid(only oneunit of CHO).The complex forms areGloboside and Ganglioside(2-9units of CHO).They are found inouter leaflet of plasma membraneand contribute to cell surface.
• Biological Importance of Lipids:1.They are more palatable and storable to unlimited amount compared to carbohydrates.2.They have a high-energy value (25% of body needs) and they provide more energy per gram than carbohydrates and proteins but carbohydrates are the preferable source of energy.3.Supply the essential fatty acids that cannot be synthesized by the body.4.Supply the body with fat-soluble vitamins (A, D, E and K).5.They are important constituents of the nervous system.6.Tissue fat is an essential constituent of cell membrane and nervous system. It is mainly phospholipids in nature that are not affected by starvation.
• 7-Stored lipids “depot fat” is stored in all human cells acts as:A store of energy.A pad for the internal organs to protect them from outside shocks.A subcutaneous thermal insulator against loss of body heat.8-Lipoproteins, which are complex of lipids and proteins, are important cellular constituents that present both in the cellular and subcellular membranes.9-Cholesterol enters in membrane structure and is used for synthesis of sexual hormones, adrenal cortical hormones, vitamin D3 and bile acids.10- Lipids provide bases for dealing with diseases such as obesity, atherosclerosis, lipid-storage diseases, essential fatty acid deficiency, respiratory distress syndrome,
Essential fatty acids EFAs:Definition: They are essential fatty acids that can not be synthesized in the human body and must be taken in adequate amounts in the diet. They are required for normal growth and metabolism. They are PUFA 2-Linoleic acid: C18:29, 12, also named w-6 which is precursor for Arachidonic acid. It is the absolute EFAs2-Linolenic acid: also named w -3(n-6), decreases TGs &bl.pressure C18:39, 12, 15, 3-Arachidonic acid: also named w-6(n-6) which is the substrate for Prostaglandin synthesis. These decreases LDL-C and protects against CAD.C20:45, 8, 11, 14.
refers to the numbering from the –COOH terminalw (omega) refers to the numbering from the –CH3 end. Source: vegetable oils such as corn oil, linseed oil, peanut oil, olive oil, cottonseed oil, soybean oil and many other plant oils, cod liver oil and animal fats.Deficiency: Their deficiency in the diet leads to nutrition deficiency disease. Its symptoms include: poor growth and health with susceptibility to infections, dermatitis, decreased capacity to reproduce, impaired transport of lipids, fatty liver, and lowered resistance to stress.
• Function of Essential Fatty Acids: They are useful in the treatment of atherosclerosis by help transporting blood cholesterol and lowering it and transporting triglycerides. The hormones are synthesized from them.They enter in structure of all cellular and subcellular membranes and the transporting plasma phospholipids.They are essential for skin integrity, normal growth and reproduction.They have an important role in blood clotting (intrinsic factor).Important in preventing and treating fatty liver.Important role in health of the retina and vision.They can be oxidized for energy production.