Lipid metabolism By Dr. Hoda Gad

OBJECTIVES BY THE END OF THESE LECTURES, STUDENT SHOULD BE ABLE TO:  Understand the structure of lipids including  Fatty acids (their different numbering methods & the essential fatty acids),  Triacylglycerols, phospholipids & cholesterol  Understand how lipids are digested, absorbed and transported in the blood.  Know how fatty acids are synthesized and oxidized  Identify the types of ketone bodies, how they are synthesized by the liver, how they are utilization by the peripheral tissues to produce energy and their excessive production in diabetes mellitus

 Know how triacylglycerols, the major form of stored energy, are formed & mobilized from their storage sites  Differentiate between the different lipases involved in lipid metabolism.  Know how cholesterol is synthesized in human body cell and its regulation.  know the types, composition & metabolism of plasma lipoproteins and how they can be separated from a plasma sample

LIPID CHEMISTRY Definition & properties  They are naturally occurring substances, water insoluble, but soluble in non-polar solvents e.g. ether  Therefore they are transported in the blood by specific proteins called lipoprpteins Importance & functions 1. Major source of energy for the body. 2. Source of fat soluble vitamins. 3. Source of essential fatty acids 4. Essential components of cell membranes.

Classes of important lipids A) Fatty acids Properties of fatty acids: F.A is a hydrocarbon chain with one carboxyl group hydrophobic R-CooH hydrophilic head hydrocarbon chain – Example: CH3-CH2-CH2-CH2-CH2-COOH Often un-branched except few F.As e.g., phytanic acid Mostly contain even number of carbon atoms They are either saturated or unsaturated They may be essential or non essential

Saturated FA: They do not contain carbon-carbon double bonds They are either – Short chain (2-10 C) – Long chain (>10C) Their general formula is CH3–(CH2)n–COOH where n= umber of CH2 groups. Example of short chain saturated FA: Butyric acid (4C): CH3–CH2–CH2–COOH Examples of long chain saturated FA: Palmitic acid (16C ): CH3–(CH2) 14 –COOH Stearic acid (18C): CH3–(CH2) 16 –COOH

Unsaturated fatty acids: They contain carbon-carbon double bonds They are either – Monounsaturated (one double bond) – Polyunsaturated (more than 1 double bond) Example of monounsaturated FA: Oleic acid 18C (18: 1; ∆ 9 ) Examples of polyunsaturated FA: a) Linoleic acid 18C (18: 2; ∆ 9,12 ) b) Linolenic acid 18C (18:3; ∆ 9,12, 15 ) c) Arachidonic acid 20C (20: 4; ∆ 5,8, 11,14 )

Essential F.A Must be supplied in the diet because the body can not form them They are present mainly in vegetable oils They are the polyunsaturated fatty acids: » linoleic acid » linolenic acid Arachidonic acid (20C) becomes essential only if linoleic acid is deficient Non essential F.A They can be formed in the body Example of non essential FA palmitic acid

How to number the carbon atoms in FA?  Counting from the carboxylic group which will be considered as carbon no 1  Counting from the carbon next to the carboxylic group which will be numbered as α and the following carbons as β, γ …etc  Counting from the methyl group (omega numbering) which will be considered as carbon no 1 and the carbon next to it will be carbon no CH3-CH2-CH2-CH2-CH2-COOH ε δ γ β α ω 1 ω 2 ω 3 ω 4 ω 5 ω 6 Caproic acid (6C)

The numeric designations for fatty acids:  First, write the number of carbon atoms in the fatty acid  Then, write the number and sites of double bonds  E.g., palmitic acid, 16-carbon fatty acid with no double bonds, is designated by (16: 0).  2 systems for designating the unsaturated fatty acid 1.The Delta system (∆): – Oleic acid is written as 18:1 ∆ 9 indicating that oleic acid contains (18) carbon atoms & one double bond (1) between carbon number 9 and carbon number 10 starting numbering from carboxyl carbon COOH which is (C1) 2.The omega system (ω): – Oleic acid may be written as 18:1, ω 9 indicating a double bond between carbon number 9 and carbon number 10 starting numbering from the omega carbon (CH3) which is C1.

1-The Delta system (∆) H methyl ω9ω9 2- The omega system (ω)

B) TRIACYLGLYCEROL  They are esters of 3 fatty acids with the alcohol glycerol: - R1 is saturated F.A - R2 is unsaturated F.A - R3 is saturated or unsaturated F.A  They are the most common type of lipids in the body  They are the storage form of lipid as it is tightly packed  If derived from animal sources, they would contain saturated FA,  If derived from plant sources; they would contain unsaturated fatty acids

Triacylglycerol

C) CHOLESTEROL  Monohydric alcohol present in animal tissues  Precursor for many important compounds such as vitamin D and steroid hormones  Essential component of membranes  The body can synthesize approximately half of the daily body needs.

Some Cholesterol Derivatives

D) PHOSPHOLIPIDS Major component of cell membranes Types: 1.Glycerophospholipids: more common  Formed of glycerol, 2 F.A, phosphoric acid & base  Bases are choline, ethanolamine, serine & inositol  Main types of glycerophospholipids:  Phosphatidylcholine (lecithin)  phosphatidylethanolamine (cephaline),  Phosphatidylserine  phosphatidylinositol 2.Sphingomyelins:  In myelin sheaths of nervous tissues  Formed of sphingosine, F.A, phosphoric acid & choline

Glycerophospholipids Phosphatidyl serine Phosphatidyl ethanolamine (Cephalin) Phosphatidyl inositol Phosphatidyl choline (lecithin)

E) GLYCOLIPIDS Composed of Sphingosine + FA+ Carbohydrate Sphingosine + FA is called Ceramide So, they are composed of ceramide + carbohydrate Main types: I– Cerebrosides Carbohydrate is 1 glucose or 1 galactose II– Gangliosides Carbohydrate is a chain of at least 3 sugars Sphingosine F.A glucose or galactose Cerebrosides Sphingosine F.A glucose galactose sialic acid Gangliosides

F) LIPOPROTEINS  Composed of lipids and proteins  They transport lipid in blood  4 main types:  Chylomicrons (CM)  Very low density lipoproteins (VLDL)  Low density lipoproteins (LDL)  High density lipoproteins (HDL)