Digestion & Absorption of lipids

Gandham. Rajeev

• The major dietary lipids are triacylglycerol, cholesterol &

phospholipids

• The average normal Indian diet contains about 20-30 g of

lipids/day

• Digestion in Stomach:

• The lingual lipase from the mouth enters stomach along with

the food

• It has an optimum pH of 2.5-5

• The enzyme active in the stomach

• It acts on short chain triglycerides (SCT)

• SCTs are present in milk, butter and ghee

• The action of lingual lipase is more significant in the newborns

• Gastric lipase:

• Gastric lipase is acid stable, with an optimum pH around 5.4

• It is secreted by chief cells, the secretion is stimulated by

gastrin.

• Upto 30% digestion of triglycerides occurs in stomach

• Emulsification of lipids in the small intestine:

• Emulsification is a prerequisite for digestion of lipids

• The lipids are dispersed into smaller droplets; surface

tension is reduced; and surface area of droplets is increased

• This process is favoured by:

1. Bile salts (detergent action)

2. Peristalsis (mechanical mixing)

3. Phospholipids

• Bile salts:

• The bile salts are sodium glycocholate & sodium taurocholate

• Bile salts are the biological detergents synthesized from

cholesterol in the liver

• They are secreted with bile into the duodenum

• Bile salts possess steroid nucleus, the side chain is attached to

either glycine (glycocholic acid) or taurine (taurocholic acid)

• Bile salts are the most effective biological emulsifying agents

• They interact with lipid particles and the aqueous duodenal

contents and convert them into smaller particles (emulsified

droplets)

• The bile salts lower surface tension

• The emulsification increases the surface area of the particles

for enhanced activity of enzymes

• Surfactant action of degraded lipids:

• The initial digestive products of lipids (catalysed by lipase), free

fatty acids, monoacylglycerols promote emulsification

• These compounds along with phospholipids are known as

surfactants

• Surfactants get absorbed to the water-lipid interfaces & increase

the interfacial area of lipid droplets

• Mechanical mixing due to peristalsis also helps in the

emulsification

Bile salts as emulsifying agents interact with the dietary lipid particles and the aqueous duodenal contents, thereby stabilizing the lipid particles as they become smaller

Emulsification by bile salts

• Digestion of lipids by pancreatic enzymes:

• The pancreatic enzymes responsible for the degradation of

dietary TAGs, cholesteryl esters & phospholipids

• Digestion of Triglycerides:

• Pancreatic lipase hydrolyse the fatty acids esterified to the 1st

& 3rd carbon atom of glycerol forming 2-monoacylglycerol &

two molecules of fatty acid

• Isomerase shifts the ester bond from position 2 to 1

• The bond in the 1st position is then hydrolysed by the lipase to

form free glycerol & fatty acid

• The major end products of the digestion of TAG are 2-MAG

(78%), 1-MAG (6%), glycerol and fatty acids (14%)

• Co-lipase: It is a small protein molecule

• The activity of pancreatic lipase is inhibited by bile acids in the

small intestine & this problem is overcome by colipase

• Also secreted by pancreas as pro-colipase & converted to

active form by trypsin

• Colipase binds at the lipid-aqueous interface & helps to anchor

& stabilize lipase

• Complete hydrolysis of triglyceride

• In the intestines, generally fats are only partially hydrolysed

Emulsification & digestion of TAGs

• Lipid esterase:

• It is a less specific enzyme present in pancreatic juice

• lt acts on monoacylglycerols, cholesteryl esters, vitamin esters

etc. to liberate free fatty acids

• The bile acid is essential for the activity of lipid esterase

• Degradation of cholesteryl esters:

• Pancreatic cholesterol esterase (cholesteryl ester hydrolase)

cleaves cholesteryl esters to cholesterol & free fatty acids

Physiologically important lipases

Lipase Site of action Preferred substrate Product(s)

Lingual / acid stable lipaseMouth , stomach TAGS with medium chain FAS FFA+DAG

Pancreatic lipase + co-lipase Small intestine TAGS with long chain FAS FFA+2MAG

Intestinal lipase with bile acids Small intestine TAGS with medium chain FAS 2FFA+glycerol

Phospholipase A2 + bile acids Small intestine PLs with unsat. FA at position 2Unsat FFA lysolecithin

Lipoprotein lipase insulin (+) Capillary walls TAGs in chylomicron or VLDL FFA+ glycerol

Hormone sensitive lipase Adipose cell TAG stored in adipose cells FFA+ glycerol

• Degradation of phospholipids:

• Phospholipases are enzymes responsible for the hydrolysis

of phospholipids

• Pancreatic juice is rich in phospholipase A 2 which cleaves

the fatty acid at the 2nd position of phospholipids

• The products are a free fatty acid and a lysophospholipid

• Phospholipase A2 is secreted as a zymogen which is

activated in the intestine by the action of trypsin

Phospholipid Degradation

• Absorption of lipids:

• Lipolytic theory put forth by Verzar:

• According to this, fats are completely hydrolysed to glycerol & FFA

• These are absorbed either as soaps or in association with bile salts

• Partition theory proposed by Frazer:

• According to this, digestion of TAGs is partial & not complete

• The partially digested TAGs in association with bile salts, form

emulsion

• Lipids are taken up by the intestinal mucosal cells

• Bergstrom theory:

• Long chain fatty acids (>14 carbons) are absorbed to the

lymph & not directly to the blood

• Mixed Micelle Formation:

• The products of digestion are 2-monoglycerides, long chain

fatty acids, cholesterol, phospholipids and lysophospholipids

are incorporated into molecular aggregates to form mixed

micelle

• Micelles are spherical particles with a hydrophilic exterior &

hydrophobic interior core

Miscellar formation

• Due to detergent action, the bile salts help to form micellar

aggregates

• Micellar formation is essential for the absorption of fat-soluble

vitamins such as vitamin A, D, E and K

• The micelles are aligned at the microvillous surface of the

jejunal mucosa

• Fatty acids, 2-MAG and other digested products passively

diffuse into the mucosal cell

• Synthesis of lipids in intestinal mucosal cells:

• The fatty acids of short & medium chain length (<10 carbons),

after their absorption into the intestinal cells, do not undergo

any modification

• They enter the portal circulation & are transported to the liver

in a bound form to albumin

• Re-esterification Inside the Mucosal Cell:

• Inside the intestinal mucosal cell, the long chain fatty acids are

re-esterified to form triglycerides

• The fatty acids are first activated to fatty acyl CoA by the

enzyme, acyl CoA synthetase or thiokinase & requires energy

• Two, such activated FAS react with monoacyl glycerol (MAG)

to form the triglyceride

• Majority of molecules follow this MAG pathway

• Free glycerol absorbed from intestinal lumen directly enters

into the blood stream

• Free glycerol is not available for re-esterification

• But the cells can convert glucose to glycerol phosphate &

add 3 molecules of acyl groups to synthesize TAG

Absorption of fat as chylomicrons

Absorption of fatty acids

• Long chain fatty acids are absorbed

into the intestinal cell wall, they are

re-esterified, made into

chylomicrons & enter into

lymphatics

• Short chain fatty acids are directly

absorbed into blood capillaries

• Bile acids are reabsorbed into

portal vein

• Chylomicrons:

• The lipids that are resynthesized in the intestinal cells are

hydrophobic in nature

• They are put together as lipid droplets and surrounded by a

thin layer consisting of mostly apolipoproteins (A1 and B-48) &

phospholipids

• This package of lipids enveloped in the layer stabilizes the

droplets and increases their solubility

• These particles are known as chylomicrons

• Chylomicrons migrate to the plasma membrane of intestinal

mucosal cells

• They are released into the lymphatic vessels by exocytosis

• The presence of chylomicrons (Greek; chylos-juice) gives the

lymph a milky appearance, observed after a lipid-rich meal

• Chylomicrons enter the large body veins via the thoracic duct

• Blood from here flows to the heart & then to the peripheral

tissues (muscle, adipose tissue) & finally, to the liver

Formation & transport of chylomicrons

• Size: 0.1–1 µm

• Averagecomposition

• TG (84%)

• Cholesterol(2%)

• Ester Cholesterol (4%)

• Phospholipid (8%)

• Apo lipoproteins (2%)

Formation & transport of chylomicrons

Transport & utilization of chylomicrons

Clinical significance of Chylomicron synthesis & utilization

• Defective synthesis- Due to deficiency of apo-B 48 protein.

• The triglyceride may accumulate in intestinal cells.

• Chyluria- Due to an abnormal connection between urinary tract

& lymphatic drainage system of the intestines, forming Chylous

fistula. Characterized by passage of Milky urine.

• Chylothorax- There is an abnormal connection between pleural

space and the lymphatic drainage of small intestine resulting in

accumulation of lymph in pleural cavity giving Milky pleural

effusion

• Absorption of short chain fatty acids:

• Short chain fatty acids (SCFA) & medium chain fatty acids

(MCFA) do not need re-esterification

• They can directly enter into blood vessels, then to portal vein,

finally to liver where they are immediately utilised for energy

• Their absorption is rapid

• Abnormalities in lipid digestion & Absorption:

• Defective digestion:

• In steatorrhea, daily excretion of fat in feces is >6 g/day

• It is due to chronic diseases of pancreas

• In such cases, unsplit fat is seen in feces

• Defective absorption:

• If the absorption alone is defective, most of the fat in feces

may be split fat, i.e. fatty acids and monoglycerides

• Celiac disease

• Surgical removal of intestine

• Obstruction of bile duct:

• Due to gall stones, tumors of head of pancreas, enlarged

lymph glands, etc.

• The result is deficiency of bile salts.

• TAGs with short chain and medium chain fatty acids are

digested & absorbed properly, they do not require

micellerisation for absorption

• Chyluria:

• There is an abnormal connection between the urinary tract &

lymphatic drainage system of the intestine.

• Urine appears milky due to lipid droplets

• Chylothorax can result from an abnormal connection

between the pleural cavity and thoracic duct

• Fate of Chylomicrons:

• The absorbed (exogenous) TAGs are transported in blood as

chylomicrons & taken up by adipose tissue & liver

• Liver synthesizes endogenous triglycerides

• These are transported as VLDL & are deposited in adipose

tissue

• During starvation states, TAGs in adipose tissue are

hydrolyzed to produce free fatty acids

• In the blood, they are transported, complexed with albumin

• These free fatty acids are taken up by the cells & are then

oxidised to get energy

Reference books

• Textbook of Biochemistry - Dr.U.Satyanarayana

• Textbook of Biochemistry - DM.Vasudevan

• Textbook of Medical Biochemistry - MN Chatterjea

Thank You