Lipid metabolism Series 1

Lipid

Organic molecules which are soluble in organic non-polar solvents and are sparingly soluble in aqueous solutions. Commonly associated with protection from loss of moisture, creams and camels humps.

Classification

5 general groupings, based on their physical properties (like solubility in organic solvents):

1. Fatty acids and their derivatives: saturated, unsaturated and eicosanoids.

2. Esters of fatty acids and glycerol: triglycerides, phosphoglycerides

3. Lipids without glycerols: sphingolipids.

4. Sterol derivatives: cholestrol, steroid hormones and vitamin D

5. Terpene and isoprenoid derivatives.

Functions

1. Fatty acids and their derivatives (especially triacylgkycerols) are high energy storage molecules, 6x more energy and weight of glycogen- hydrophobic, anhydrous nature.

2. Layers of lipids form good insulators, and limited metabolic activity of adipose tissue - reduced heat exchange.

3. Membranes are generally composed of fatty acid derivatives - hydrophobic barrier.

4. Can be used as signaling molecules, such as prostaglandin and steroids and as enzyme Cofactor

5. Precursors of several hormones and some fat-soluble vitamins: A,D,E,K

Digestion

90% of normal diet lipids are TAGs (triacylglycerol) and some digestion starts in stomach by some lipase and is oxidized into CO2 and H2O

Bile salts

Possesses both hydrophobic and hydrophilic surface thus allowing for oil-water interface.

Emulsification through detergent action of TAGs- results in forming smaller units termed micelles. This allows for water soluble pancreatic lipase to digest and also facilitates absorption into intestinal mucosa.

Absorption

Stabilization of Michells is crucial before uptake and absorption. Thus mixed micelles would comprise monoacylglycerols, lysophosphoglycerols, long chain FAs plus bile salts.

Achieved by dissociation of micelles where the salts remain in the lumen while the digested lipids are taken up by simple transfer from micellar enviroment into aqueous one.

Action of lipases

Lipases hydrolyse the ester linkages of TAG at positions 1 and 3 to yield 2 monoacyl glycerol and 2 fatty acids

Steatorrhea

Pale, bulky, non-smelly stool. Clinical implication. Low bile production/ secretions (biliary duct blockage/ liver disease). Severe reduced absorption of dietary fats and fat soluble vitamins from digestive tract into the bloodstream. Sufficient levels of fats, cholesterol and vitamins are necessary for normal growth, development, and maintenance of the body’s cells and tissues particularly nerve cells.

Transportation

TAGs are hydrolyzed in periphery by lipase.

1. Glycerols are transported back to liver and kidney

2. FA uptake bound to serum albumin for Ɓ-oxidation in peripheral tissues.

3. One small enough reabsorption into the epithelial cells via re-esterification of fatty acids back into Tags. These combine with lipoprotein released by the intestines to produce chylomicrons (in ER and Golgi apparatus) -75nm diameter, which acts as serum transport particles for TAGs. Released into lymph or blood stream and are either taken up by the liver or delivered to adipose tissue. TAGs made by liver are packaged into VLDLs and released into the blood.

Lipoproteins

Chylomicrons- least dense form. VLDL (very low density lipoproteins). LDL (low density lipoproteins). HDL (high density lipoprotein) [aka cholesterol scavengers, associated with reduced risk of heary disease].

Apolipoproteins refer to proteins in lipoproteins. Lipoprotein lipase- enzyme located in capillary walls; removes fatty acids from chylomicrons and VLDLs.

Clinical implication: abetalipoproteinemia.