Lipid Metabolism

By

Muhammad Azhar Chishti

Dr. M. Azhar Chishti

Universityof Toronto Canada

LIPIDS• Lipids are heterogeneous groups of relatively

water insoluble molecules related to fatty acids.

• They are soluble in non-polar solvents such as Benzene, Ether, Chloroform and acetone.

They are insoluble and mostly in the form ofA: Compartmentalized of membrane associated

lipid (adipocyte)B. Plasma: Associated with protein--

Lipoprotein

LIPIDSFunction of Lipid:

• Major source of energy ( 1gms = 9Kcal)

• Hydrophobic barrier (cell membranes)

• Fat soluble vitamins – coenzymes, regulatory function

• PG & steroid hormones are regulatory role in body homeostasis

• Imbalance lead to diseases like Obesity and atherosclerosis.

Classification of lipids

A: Simple lipids such as fats and waxesB: Compound lipids such as phospholipids, Glycolipids,

LipolipidsC: Derived lipids are after hydrolysis associated lipids

are formed mainly from an alcohol and FA combined by an ester linkage.Fatty Acid Hydrophobic CH3(CH2)n:COO-- Hydrophilic

Hydrocarbon chain Carboxyl group (COOH)

Digestion:

• An adult ingest 60-150gms of lipid/day • 90% is triacylglycerol (called triglyceride)• 10% is cholesterol, cholesterol esters, phospholipids

and free FA.

Digestion start in stomach • Catalyzed by acid stable lipase (lingual

lipase) back of tougue• Short chain TG molecules (less than 12

corbons as milk fat) hydrolyzed• These TG molecules also hydrolyzed by

gastric lipase• Acid lipase play major role in lipid digestion

to provide energy to neonates• Lingual and gastric acid lipases mainly

hydrolyzed TG molecules in patients of cystic fibrosis with no pancreatic lipase.

Emulsification of dietary lipid• This process occurred in duodenum• Emulsification increase the surface area of

hydrophobic lipid so digestive enzymes can work at interface of lipid and surrounding by water solution.

Emulsification is by 2 complimentary mechanisms asA: Detergents properties of bile salts. These are made

in liver and store in gall bladder and release to duodenum by bile duct.

B: Mechanical mixing by peristalsis.These emulsifying agents stabilize the lipid particles as they become smaller and prevent then to more coalescing or uniting together.

Bile salt are glycocholic acid that is cholic acid and glycine.

Degradation by pancreatic enzymesA: Triacylglycerol degradation:• TG molecule is too long cannot taken up by mucosal and

intestinal villi.• Pancreatic lipase and estrase remove 2 fatty acid at 1,3 and

make 2 monoacylglycerol.• malabsorption in severe pancreatic deficiency as in cystic

fibrosis.• colipaseB: Cholesteryl ester degradation:• Dietary cholesterol is present in free form with 10-15%

esterified form.• It is hydrolyzed by pancreatic cholesterol hydrolase

(cholesterol estrase)• End product is cholesterol + fatty acids.• Activity greatly increased in the presence of bile salts.

C: Phospholipid deradation:

• Pancreatic juice is rich in procolipase is activated by trypsin and required bile salts for optimal activity.

• Procolipase remove one FA of phospholipid result in lysophospholipid.

• phosphotidylcholine ---- procolipase--- lysophosphotidylcholine.

• lysophosphotidylcholine—lysophospholipase—glycerylphosphoryl base

• Excreated in feces, further degraded or absorbed.

D: Control of Lipid digestion:

• Pancreatic secretion is controlled by hormone Chlolecystokinin (CCK) when lipids enter in small intestine by mucosa of jejunium and duodenium.

• CCK acts on gall bladder and exocrine cells of pancreas to release enzymes

• CCK also decreases gastric motility to slow release of gastric contents.

• Secretin release for small intestine in response to low pH of chyme entering in intestine.

• Secretin causes the pancreas and the liver to release watery solution rich in carbonate that neutralize pH for digestive activity of pancreatic enzymes.

Absorption of Lipid:

• Dietary degraded products of lipid mix with bile salts and form mixed micelles

• Mixed micelle are disk shape clusters of amphipathic lipid with hydrophobic group inside and yhdrophilic group outside of cluster.

• They are soluble in instertinal lumen and absorb through the brush boders membranes of enterocyte

• These membranes is sepreted from the liquid contents in intestinal lumen by unstirred water layer.

• Hydrophilic surface assist in transport of hydrophobic lipid by unstirred water layer of brush boders and absorbed.

• Short or medium chain FA do’t need micelle.• Dietary therapy for individual with malabsorption.

Resynthesis of TG and Cholesteryl esters :

• Mixture of absorbed lipid by enterocyte move to ER for biosynthesis of complex lipid.

• FA FAacyl-CoA synthase FA acyl CoA• 2-monoacylglycerol mono&di acyltransferase

Triacylglycerol• Lysophosphlipid acyltransferase Phospholipid• Cholesterol ACAT Cholesterol ester• Long chain FA undergo these process• Short chain FA release into portal circulation and

carried to liver by serum albumin.

Secretion of Lipids from Entrocytes as Chylomicron

Malabsorption of lipid :

• Malabsorption result in increase lipid in feces called steatorrhea.

• Soluble vitamins (A, D, E,K ) and essential FA

• Cystic fibrosis causing poor digestion

• Shortened bowl leasd decrease absorption.

Secretion of lipid :• Newly synthesized TG and cholesteryl esters are

very hydrophobic and deposit in watery environment.

• These need to packed as lipid droplet covered by a layer composed of phospholipid, unesterfied cholesterol and protein.

• This layer stabilize the droplet and help in absorption and prevent clustering.

• Milky colour of lymph.• The lymph is called Cyle and these particles called

cylomicron.• These move into lacteals (LV of villi) then

Lamphatics system to thoracis ducts and finally enter into blood.

Use of dietary lipid to tissues:• TG contained in chylomicrons is broken

down in capilleries of skeletal muscles and adipose tissues of heart, liver, kidneys.

• TG is broken down into FA and glycerol by lipoprotein lipase.

• This enzyme is synthesize by adipocyte and muscle cells and secreted in lumen of capilleries of pheripheral blood vessels.

• Familial lipoprotein lipase deficiency (ARD) lead into massive chylomicronemia.

1. Fate of free Fatty acids:

FFA from hydrolysis enter in muscle call or adipocyte otherwise transported to blood with serum albumin until taken up by cells.

Most cells oxidize FA to produce energy.

Adepocyte also reesterify FFA to produce TG molecules and stored until body needed.

2. Fate of Glycerol:

Chylomicron Metabolism