Lipid- Digestion & Absorption

8/3/2019 Lipid- Digestion & Absorption

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DIETARY FAT :- 90% is normally triglycerides.

- Cholesterol,

Cholesteryl esters,

Phospholipids, and

Unesterified fatty acids.

Average Normal Indian Diet: 20-30 gm/dayWestern Diet: 2 or 3 times of this



Challenges Lipids are not water soluble

Triglycerides too large to be absorbed

Digestive solution

Triglycerides mix with bile and pancreatic secretions

Emulsification and digestion



IN STOMACH Lingual lipase:

- Active at low ph (pH 2.5 – 5)

- Short chain TGS.

- In milk, butter and ghee.

Gastric lipase:

- Up to 30% of TGS



IN SMALL INTESTINE

1.Emulisification:

Dispersion of lipids into small droplets

- Bile salts ( detergent action )

Function to transport cholesterol in the digestive system

- Peristalsis ( mechanical mixing )

- phospholipids



2. Digestion:

Pancreatic juice:

- Pancreatic lipase

- Cholesterol estarase

- Phospholipase A2

- Colipase

Lipolytic enzymes

colipaselipase

TG particle



Hydrolysis of lipids

Triglycerides (TG)

TG + H2O → Diglyceride + fatty acid (FA)

Diglyceride + H2O → Monoglyceride (MG) + FA

2+

2 H2O

lipase

OO

O

O RR

O R

OOH

OOH

RO R

OO

–

+ 2 H+



Cholesterol esters & phospholipids* (PL)↓ esterase ↓ phospholipases

FA + cholesterol (chol) FA + lyso PL

In all cases, products are more polar than reactants

OO

O

P OR

O R

OO

OR

–

* biliary & dietary



Physiologically important lipases

Lipase Site of action Preferred substrate Product(s)

Lingual / acid stablelipase

Mouth , stomach TAGS with medchain FA S

FFA+DAG

Pancreatic lipase +

co-lipase

Small intestine TAGS with long

chain FA SFFA+2MAG

Intestinal lipase withbile acids

Small intestine TAGS with med chainFA S

2FFA+glycerol

Phospholipase A 2 +

bile acids

Small intestine PLs with unsat. FA

on position 2

Unsat FFA

lysolecithin

Lipoprotien lipaseinsulin (+)

Capillary walls TAGs in chylomicronor VLDL

FFA+glycerol

Hormone sensitive

lipase

Adipose cell TAG stored in

adipose cells

FFA+glycerol



3. Absorption: Bile: Produced in liver, stored in gallbladder

Alkaline solution composed of:

Bile salts

Cholesterol Lecithin

Bilirubin

Bile secretion stimulated by

secretin (target: liver)

CCK (target: liver & gall bladder)

Absorbed bile salts



Bile salts: synthesis, secretion

Synthesized in the liver.

cholesterol

Bile acid

Bile acyl-CoA

+ amino acid ( glycine / taurine )

Bile salt



Biliary Lipid Secretion

Sinusoidal Membrane

Blood Hepatocyte

Canalicular Membrane

Bile Salt

ABCG5/G8

Cholesterol

ABCB4Phospholipid

ABCB11

Bile



Biliary Lipids

Daily Secretion (g)Lipid Class

Bile salts

Phospholipids

Cholesterol

24

11

2



Structure of Biliary and Intestinal Micelles

Cholesterol

BileSalt

Phospholipid



Biliary Lipid Transport

Duodenum

Jejunum

Ileum

Colon

BiliaryTransport

andStorage

Liver



Fat Digestion

Duodenum

Jejunum

Ileum

Colon

BiliaryTransport

and

Storage

Liver



Fat Digestion

I I

II

III

III II

I

Fatty Acids +

Lysophospholipid

Phospholipids

III

Triglycerides

Fatty Acids +

Monoglycerides

I I

II

III

III

DietaryCholesterol ester

Fattyacids+cholesterol



Fat Absorption

Duodenum

Jejunum

Ileum

BiliaryTransport

and

Storage

Colon

Liver

Ab ti f l



Absorption from lumen

brush bordermembrane

microvillus

diffusionof micelles

throughunstirredlayer

well-mixedluminalcontents

monoglycerides

lysophos-pholipids

chol

fatty acids

unstirred layer

cytosol

Movement of lipid digestion products (FA, MG, etc) across mucosal

plasma membrane by simple diffusion of monomers

Absorptionalso occursvia fatty acid transfer protein (FATP)

Microvilliprovide verylarge absorbingsurface, butconvolutions &glycocalyxproduceunstirred layer

Adapted from

Fig. 34

-14 (B & L

)

FATP



Absorption: role of micelles

Unstirred layer

200-500 μm thick

Prevents peristalticmixing from movingluminal contents closeto cell surface

Crossed by micelle diffusion

because of very low solubility of

lipid molecules & very large distance,

absorption would be very slow

without micelles

Mixed micelles act as:

carriers of lipid monomers (FA, MG, chol, vit. A, D, E, K)

reservoirs: as monomers absorbed, they are rapidly replaced by dissociation

from micelles



Lymph Enterocyte

Intestinal

Lumen

Cholesterol Absorption

CholesterylEster

ACAT

Cholesterol NPC1L1

ABCG5/

G8



Lymph Enterocyte IntestinalLumen

Triglyceride Absorption

2 Fatty Acid+

Monoglyceride

DGAT

Triglyceride



Lymph Enterocyte

IntestinalLumen

Phospholipid Absorption

Phospholipid

Fatty Acid+

Lysophospholipid



Enterohepatic circulation(bile salt recycling)

Bile salts absorbed

toward end of ileum

Absorption by Na+ – driven cotransport

Na+ – bile salt symport

Carried in portal blood

bound to albumin

Added to bile again by

liver & secreted again

Typically make 3-4

roundtrips during

average meal

cholesterolbile salts

Sherwood, Fig.16-17



ormation and secretion of (A) chylomicron in intestinal and

(B) VLDL in Hepatic cell.



Packaging for transport

chylomicrons Particles for

transport of lipids

to liver &

adipocytes

Size: 0.1 – 1 µm

Averagecomposition:

TG (84%)

chol (2%)

cholE (4%)PL (8%) apolipoproteins (2%)

apolipo-proteins

cholE, TG

chol PL

PL

Lehninger et al.,3rd ed., Fig. 17-2



Fate of dietary lipids:

TGs: FFA + glycerol

FFA:

- FFA from TGs muscle (energy production)

adipocytes( re esterified to TGs)

Glycerol : Glycerol from TGs in liver forms glycerol 3 phosphate ( glycolysis,

gluconeogenesis)

Chylomicron remnants:

Endocytosed into liver and are hydrolysed to their component parts and recycled by

the body.

- If this process is decreased due to impaired binding to the receptor on liver, they

accumulate in the plasma leading to type III hyperlipoproteinemia



Stomach

gastric mobility

Smallintesti

ne

Dietary lipids

Degradation of dietary lipids

cholecytokinin

-

GutEndocrine

cells(enlarged)

+

Secretin(in blood)

pancreas

+

bicarbonate

Pancreaticlipase

bile

Gall bladder

+

Hormonal control

+



Abnormalities of maldigestion/malabsorption

The main causes of malabsorption ( STEATORRHEA ) under 3 catagories:

1. Disorders of intraluminal digestion:

2.Disorders of transport into mucosal cells:

a) Altered gastric function Post gastrectomy syndrome

b) Pancreatic insufficiency Chronic pancreatitisCystic fibrosis

Pancreatic cancerc) Bile acid deficiency Disease/resection of terminal ileum

Small bowel bacterial over growth.

a) Generalised disorders due toreduction in absorptive surface area.

Celiac diseaseTropical sprue

b) Specific disorders Hypolactasia Vit B12 in pernicious anemiaZn in acrodermatitis enteropathica



3. Disorders of transport out of the mucosal cell:

Clinical presentation of the patient suffering from malabsorption /mal digestion

classically includes the following features:

- Evidence of general ill health

- Isolated nutritional deficiencies

- Abdominal symptoms- Watery diarrhea and possibly steatorrhea

a) Blockage of the lymphatics Abdominal lymphomaPrimary lymphangiectasia

b) Inherited disorders A-β-lipoprotienemia



Tests for assessing fat absorption and malabsorption:1.Fat globules ( fecal microscopy )

2. Mixed chain triglyceride breath test

3. Measurement of fecal fat

Tests for pancreatic function:

Pancreaolauryl test , fecal elastase.

S f li id di ti



Summary of lipid digestion

& absorption

TGMGFA

MG

FA (>10C)

FA (<12C)

chylomicron

BILESALTS

chylomicron

mixedmicelle

albuminBILESALTS

FA

lipase-

colipase

lipase-colipase

apolipoproteinsphospholipids

emulsiondroplet

BILESALTS

18

4ATPs/TG

Enterocyte

oildrop

TG

Lipid- Digestion & Absorption

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