Lipid Metabolism

Digestion & absorption

IntroductionFat is a good source of energy as 1 gm

supplies 9.1 calories, which is over double

that supplied by carbohydrates or protein.

Dietary lipids are ingested in form of

triglycerides, phosholipids, cholesterol and free fatty acids.

A minimal amount of fat is essential in our food to provide an adequate supply of the essential fatty acids.

Lipids are esters of fatty acids with various alcohols:

R-COOH + R-OH RCOOR + H2O

Fatty acid + Alcohol Ester +

Water

Fats are esters of fatty acids with glycerol called

triglycerides because they are tri-esters of glycerol

Fatty acidsThese are carboxylic acids their general formula R- COOH.

fatty acids are classified into 1. saturated 2. unsaturated fatty acids according to absence or presence of double

bonds.

1- Saturated fatty acids Saturated chain fatty acids are based on

acetic acid CH3-COOH.

no double bonds

CH3 - COOH is acetic acid,

CH3 – CH2 – COOH is propionic acid

CH3 – CH2 – CH2 – COOH butyric acid and so on.

2- Unsaturated fatty acids

They have one or more double bonds.

Biological Importance Of Lipids:

1- Energy production, dietary lipids supply the body with about 25% of calories needed every day.

2- They provide the body witha) Essential fatty acidb) Fat soluble vitaminsc) Phosphours in the form of phospholipids

3. Fats under the skin are used as insulater protecting the body against external temp.

4. Combinations of fat and protein (lipoproteins) are important cellular constituents and serve for the transport of lipids in the blood.

5. Cholestrol is used for synthesis of adrenal cortical hormones, vitamin D3 and bile acids.

Digestion of lipids1- Digestion of triglycerides: Ingested triglycerides first are

emulsified and then undergo enzymatic hydrolysis by lipase enzymes.

1- Emulsification: Breakdown of large fat globule into

small ones done in the mouth by chewing. in the stomach by peristaltic contractions. in intestine by peristaltic movement, bile

salts.

2- Digestive fat enzymes: Are lingual lipase, gastric lipase, pancreatic

lipase and intestinal lipase. The most active is pancreatic lipase.

1-Lingual lipase: Is secreted by the dorsal surface of the tongue (Ebner's glands),

but this enzyme is not of much significance in humans as compared with rat or mouse.

2-Gastric lipase (pH 3-6): In the stomach some digestion occurs by

gastric lipase

hydrolyzing triglycerides containing short, medium and unsaturated long chain fatty acids

to form FFA and 1,2 diglycerides

3-Pancreatic lipase:a) Bile salts

assist emulsification by lowering surface tension

exposing large area of triglycerides

pancreatic lipase will dissolve fatty acids.

b) Pancreatic lipase

acts on finely emulsified lipid droplets

in presence of 1- bile salts.

2- colipase (a protein present in pancreatic

secretion).

3- phospholipase A2 (Ca++ is necessary for

phospholipase A2 activity).

c) Pancreatic lipase hydrolyses the primary ester bond with the production of 2FFA + β-monoglyceride.

d) Hydrolysis of monoglyceride requires transfer of the FA from beta to alpha carbons of glycerol by specific isomerase enzyme.

this process is very slow. So the major digestion products of TG are β-monoglyceride and FA.

4-Intestinal lipase: Act within intestinal mucosal cells where it may

hydrolyse primary monoglyceride

glycerol and FFA.

2-Digestion of phospholipids: Glycerophospholipids are hydrolyzed by

pancreatic enzyme phospholipase A2

which remove FA in position 2 to form lysophospholipids.

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

phosphatidate

Intestinal phospholipase

may complete the hydrolysis of lysophospholipids

glycerol + FA + phosphoric acid

3-Digestion of cholesterol esters:

Cholesterol ester are hydrolyzed by cholesterol ester hydrolase (cholesterol esterase) into FA and free cholesterol

C holestero lH O

Absorption of lipids The end products of lipid digestion are:

FA – glycerol - monoglyceride - cholesterol and lysophospholipid.

1- Short (less than 10 carbon atoms) and medium chain fatty acids (10-12C) together with free glycerol are water soluble

absorbed to the intestinal cell by diffusion and passes directly to the liver through the portal circulating.

2- monoacylglycerol + long chain fatty acids + cholesterol and lysophosphoatide

are absorbed through the plasma membrane of the intestinal cells

(jejunum and ileum) together with bile salts

forming soluble complexes with

them(Micelles).

Inside the intestinal cells: bile salts are separated and carried out to

the liver via the portal circulation and then secreted with the bile in the intestine.

This known as enterohepatic circulation of bile salts.

Inside the intestinal cells:

long chain fatty acids are activated by thiokinase enzyme (acyl COA synthetase) forming acyl COA.

Acyl CoA esterifies 2-monoacylglycerol at 1 and 3 positions T.G.

T.G are formed also from free glycerol in intestinal cells from dihydroxyacetone phosphate (from glycolysis).

Activated by glycerokinase enzyme

Resynthesis of phospholipids & cholesterol esters by combination of cholesterol and lysophospholipids absorbed with acyl-CoA.

The triglycerides, phospholipids & cholesterol ester and cholesterol bind with

a protein (apolipoprotein

B48) to form chylomicrons which enter lacteals and pass with

lymphatic drainage to the thoracic duct to reach systemic circulation.

Fate of absorbed lipid Immediately after absorption of lipids there is

turbidity of plasma due to the circulating chylomicrons (appear in plasma 2 hours after meals).

This turbidity is soon cleared by lipoprotein lipase enzyme (clearing factor).• This enzyme hydrolyses triglycerides of

chylomicrons to glycerol and FFA. • Glycerol is transported to liver to be metabolized

as carbohydrate.

Free fatty acids are carried by plasma albumin to adipose tissues liver and other tissues for metabolism.

MOST dietary fat transported to adipose for storage