LIPIDS : DIGESTION AND ABSORPTION

V.S.RAVIKIRAN, MSc.

V.S.RAVIKIRAN, MSc., Department of Biochemistry,

ASRAM Medical college, Eluru-534005.AP, India.vsravikiran2013@gmail.c

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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/day

Western Diet: 2 or 3 times of this

ChallengesLipids are not water solubleTriglycerides too large to be absorbed

Digestive solutionTriglycerides mix with bile and pancreatic secretions

Emulsification and digestion

IN STOMACHLingual 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

colipase

lipase

TG particle

Hydrolysis of lipids

Triglycerides (TG)

TG + H2O → Diglyceride + fatty acid (FA)

Diglyceride + H2O → Monoglyceride (MG) + FA

2+2 H2O

lipase

OO

OO

RR

O RO

OHO

OH

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

OP O

RO R

OO

OR

–

** biliary & dietary biliary & dietary

Physiologically important lipases

Lipase Site of action Preferred substrate

Product(s)

Lingual / acid stable lipase

Mouth , stomach TAGS with med 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 med chain FAS

2FFA+glycerol

Phospholipase A2

+ bile acidsSmall intestine PLs with unsat.

FA on position 2Unsat FFA lysolecithin

Lipoprotien lipase insulin (+)

Capillary walls TAGs in chylomicron or 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 saltsCholesterolLecithinBilirubin

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

BloodBlood HepatocyteHepatocyte

Canalicular Membrane

Bile SaltBile SaltBile SaltBile Salt

ABCG5/G8Cholesterol

ABCB4Phospholipid

ABCB11

BileBile

Biliary Lipids

Daily Secretion (g)Daily Secretion (g)Lipid ClassLipid Class

Bile salts

Phospholipids

Cholesterol

24

11

2

Structure of Biliary and Intestinal Micelles

Cholesterol

Bile Bile SaltSalt

PhospholipidPhospholipid

Biliary Lipid Transport

DuodenumDuodenum

JejunumJejunum

IleumIleum

ColonColon

BiliaryTransport

and Storage

Liver

Fat Digestion

DuodenumDuodenum

JejunumJejunum

IleumIleum

ColonColon

Biliary Transport

and Storage

Liver

Fat Digestion

I I

II

III

III II

I

III

Fatty Acids +Fatty Acids +LysophospholipidLysophospholipidFatty Acids +Fatty Acids +LysophospholipidLysophospholipid

PhospholipidsPhospholipidsPhospholipidsPhospholipids

III

TriglyceridesTriglyceridesTriglyceridesTriglycerides

Fatty Acids +Fatty Acids +MonoglyceridesMonoglyceridesFatty Acids +Fatty Acids +MonoglyceridesMonoglycerides

I

I

IIII

III

I

I I

II

III

III

DietaryDietaryCholesterol esterCholesterol esterDietaryDietaryCholesterol esterCholesterol ester

I I I

III

Fatty Fatty acids acids + + cholestecholesterolrol

Fat Absorption

DuodenumDuodenum

JejunumJejunum

IleumIleum

BiliaryTransport

and Storage

ColonColon

Liver

Absorption from lumen

brush bordermembrane

microvillus

diffusionof micelles

throughunstirredlayer

well-mixedluminalcontents

monoglycerides

lysophos-pholipids

chol

fattyacids

unstirred layer

cytosol

Movement of lipid digestion products (FA, MG, etc) across mucosal plasma membrane by simple diffusion of monomers Absorption also occurs via fatty acid transfer protein (FATP) Microvilli provide very large absorbing surface, but convolutions & glycocalyx produce unstirred layer

Adapted from Fig. 34 -14 (B & L)

FATP

Absorption: role of micelles

Unstirred layer 200-500 μm thickPrevents peristaltic

mixing from moving luminal contents close to 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

LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyteIntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen

Cholesterol Absorption

CholesterylEster

ACAT

Cholesterol

IITT

NPC1L1

ABCG5/G8

LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyte IntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen

Triglyceride Absorption

2 Fatty Acid

+

Monoglyceride

DGAT

Triglyceride

TTII

LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyte

IntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen

Phospholipid Absorption

Phospholipid

Fatty Acid

+Lysophospholipid

II

LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyteIntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen

Chylomicron Formation

With

apoB48 CholesterylEster

Triglyceride

Phospholipid

Enterohepatic circulation(bile salt recycling)

Bile salts absorbed toward end of ileum

Absorption by Na+–driven cotransportNa+–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

Formation 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 Average composition:TG (84%)chol (2%)cholE (4%)PL (8%) apolipoproteins (2%)

apolipo-proteins

cholE, TG

chol PL

Lehninger et al., 2nd ed., Fig. 16-2

PL

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

Fate of dietary lipids:TGs: FFA + glycerolFFA:

- 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

Small intesti

ne

Dietary lipids

Degradation of dietary lipids

cholecytokinin

-

GutEndocrin

e cells (enlarge

d)

+

Secretin(in blood)

pancreas

+

bicarbonate

secretesPancreatic lipase

secretes

bile

Gall bladder

secretes +

Hormonal control

+

triglycerides

Abnormalities of maldigestion/malabsorptionThe 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 fibrosisPancreatic cancer

c) Bile acid deficiency Disease/resection of terminal ileumSmall bowel bacterial over growth.

a) Generalised disorders due to reduction in absorptive surface area.

Celiac diseaseTropical sprue

b) Specific disorders HypolactasiaVit 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

Chyluria Chylothorax

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.

Summary of lipid digestion & absorption

TGMGFA

MGFA(>10C)

FA(<12C)

chylomicron

BILESALTS

chylomicron

mixedmicelle

albuminBILESALTS

FA

lipase-colipase

lipase-colipase

apolipoproteinsphospholipids

emulsiondroplet

BILESALTS

1818

4ATPs/TG

EnterocyteEnterocyteoildrop

TG

THE END

THANKS FOR YOUR ATTENTION