BIOCHEMISTRY LIPID BY Dr. Basil O M Saleh , 2 nd Class college of Medicine, Baghdad Univ.

1.Introduction 2.Cholesterol: Synthesis & Regulation Functions, Correlation with CAD 3.Lipoproteins: Definition, Metabolism &Disorders Fatty Acids: Biosynthesis, Oxidations & Disorders 4.Ketone bodies: Biosynthesis,Regulation& Ketoacidosis 5.Triglycerides and phospholipids: Biosynthesis, Functions & Hormonal regulation 6.Sphinogolipids, Glycolipids and Sphingolipidosis 7.Prostaglandins: Biosynthesis and Functions 8. Others

INTRODUCTION OBJECTIVE: 1.Definition, Structures, and Functions of Lipid Components. 2. Lipid and Cell Membranes, Essential Fatty Acids; structure & functions

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) as 1.Memebrane-associated lipids; phospholipids, free cholesterol, sphingolipids 2.Droplets in adipocytes as TGs 3.Transported in blood as lipoproteins(LPs) such as VLDL, LDL…, or in association with protein, mainly albumin as with fatty acids.

Lipids are important substances that function in 1.TGs are the major source of chemical energy ATP along with CHO, and they are the principal stored energy in human body 2.They are hydrophobic barrier that separate the EC compartment(interstitial and blood vessels) and the intracellular compartments 3. Fat soluble vitamins; K,D,E, and A 4. Steroid hormones; like sexual hormones testosterone, Estradiol 17 B ( E2), progesterone, other androgens and estrogens are derived from lipid cholesterol

5.Vitamin D 3(cholecalciferol) which is essential for normal skeleton development is synthesized from cholesterol in human body. 6. They are structural components of cell membrane and other organelle membranes like mitochonderia. THE imbalance in lipids metabolism whether increase or deficiency can lead to clinical problems of which the most important is atherosclerosis. 5.Vitamin D 3(cholecalciferol) which is essential for normal skeleton development is synthesized from cholesterol in human body. 6. They are structural components of cell membrane and other organelle membranes like mitochonderia. THE imbalance in lipids metabolism whether increase or deficiency can lead to clinical problems of which the most important is atherosclerosis.

Fatty Acids are simply linear chains of carbon-hydrogen(C-H) bonds that terminate with a carboxyl group(-COOH). The general formula of FA is RCOOH, R: CH3CH2CH2………. or CH3(CH2)n In plasma, 1. small amount of FAs are free(unesterified) mainly bound albumin? 2. the majority of plasma FAs are constituents of TGs or phospholipids(PLs) AND cholesterol ester. FAs are classified depending on the chain length: 1. short(4-6 carbon atoms), 2. medium(8-12 Cs) 3. long(> 12 Cs) FAs. The chain length ranges from 4 to 30 carbons; is most common, AND the predominant FA in human body is Palmitic acid C16.

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

Cholesterol

Lipid are classified into 1. Simple lipids (Fats & Waxes) 2.Compound or conjugated lipids 3.Derived Lipids 4.Lipid-associating substances 1. 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 CH2OCOR3 Usually R1 &R3 usually saturated, while R2 unsaturated. Glycerol+R1= Monoacylglycerol Glycerol+R1+R2+Diacylglycrol Glycerol+|R1+R2+R3= Triacylglycerol

2. Compound( Complex) lipids a. PHOSPHOLIPIDS b. Glycolipids c.Lipoproteins Phospholipids 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-base CH2OPO3-b b: is Nitrogen base

Lecithin PL is: 1. The predominant type of PL in CM 2. The source of choline component of the neurotransmitter; the Acetylcholine 3. The principal lipid component of Lung surfactant(90 % lipid and 10 % protein), its deficiency in preterm infants is associated with inadequate production or secretion of surfactant causes Respiratory Distress Syndrome(RDS), the significant cause of death in Infants.

Lecithin is made and secreted by pneumocytes to act as surfactant, decrease the surface tension of fluid lining the alveoli so reducing the pressure needed to reinflate alveoli, thereby preventing alveolar collapse(atelectasis ) 4. involved in emulsification of fat diet in small Intestine along with Bile salt. Cardiolipin PL is the principal type of PL that involved in inner mitochondrial membrane structure(important for maintenance of certain respiratory complexes).

Anti-cardiolipin ACL & Antiphospholipid APL are used in investigation of autoimmune diseases such as in abortion or dead infant delivery. Platelet activating factor PAF and Plasmalogene Are compounds that belong to PL structure but differ in containing ether linkage ROR instead of ester linkage 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 glycerol sphingosine+ Fatty acid= ceramide ceramide+NitrogenBase(e.g;choline)= Sphingolipids such as Sphingomyelin. It is an important component of myelin sheath of nerve fibers, insulates and protects neuronal fibers of the central nervous system(preventing the short circulation of nerve electrical pulse transmission).

Ceramide+ CHO= glycolipids These are another type of lipid. of which : T he simple forms are Glucosylsphingolipid and Galactosylsphingolipid(only one unit of CHO).The complex forms are Globoside and Ganglioside(2-9 units of CHO).They are found in outer leaflet of plasma membrane and 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 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, 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 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 : C18:2  9, 12, also named w-6(n-6) which is precursor for Arachidonic acid. It is the absolute EFAs 2-Linolenic acid : also named w -3(n-3), decreases TGs &bl.pressure C18:3  9, 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. C20:4  5, 8, 11, 14. 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: C18:2  9, 12, also named w-6(n-6) which is precursor for Arachidonic acid. It is the absolute EFAs 2-Linolenic acid: also named w -3(n-3), decreases TGs &bl.pressure C18:3  9, 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. C20:4  5, 8, 11, 14.

 refers to the numbering from the –COOH terminal w (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.