Gastrointestinal System

Biochemistry of Digestion
and Absorption
Three Stages of
Catabolism


 Major events involved in food digestion
and absorption
1. Mechanical homogenization & mixing of food with GIT
fluids
2. Secretion of enzymes for hydrolysis of food molecules
3. Secretion of electrolytes, acid or base to provide an
optimum environment for enzymatic digestion
4. Secretion of bile acids/salts for digestion and
absorption of lipids
5. Enzymatic hydrolysis of large food molecules
6. Transport of hydrolyzed food molecules across the
intestinal epithelial cell into blood
 Major Constituents of Saliva
Mucins
• a mixture of glycoproteins (60-85%
oligosaccharide)
• forms viscous lubricating solutions

α -Amylase
• Catalyzes the hydrolysis of only α(1→4)
glucosidic bonds of starch and glycogen
• Has minimal role in digestion

Lingual Lipase:
• Initiates hydrolysis of dietary fat in the
stomach and facilitates the duodenal-
jejunal hydrolysis of TGs.
Major Constituents of Gastric Secretions
Constitu- Source Major functions
ents
HCl (acid) Parietal Kills microbes, dissolves food particles,
cells activates pepsinogen into pepsin and
provides optimum pH for pepsin
Pepsinogens Chief cells Begins initial hydrolysis of proteins
(Pepsin) (optimum pH 2-4)
Rennin Stomach Causes milk clotting & promote its
(only in digestion by preventing rapid passage
infants) from the stomach.
Gastric Chief & An acid stable lipase that digest short
lipase mucous cells chain fatty acid
Gastrin G cells Stimulates acid secretion by stomach
Mucus Mucous cells Protects stomach, moistens food
 Major constituents of pancreatic and bile
secretions
Constituents Source Major functions
NaHCO3- Hepatocyte; Neutralizes acidic chyme in the
Centroacinar duodenum & maintains optimum
& duct cells alkaline pH for the digestive
(Pancreas) enzymes
Enzymes Acinar cells Include amylase, peptidases and
(Pancreas) lipases. Digest partially degraded
starch, proteins and lipids
Bile salts Hepatocytes Detergent mols. Stimulates
intestinal lipase and emulsify
lipids for their digestion and
absorption
 Major constituents of secretion from
small intestine
Constituents Source Major functions
Secretin S cells Stimulates NaHCO3- secretion from
exocrine pancreas

I cells Stimulates gallbladder contraction to

Cholecystoki release bile and pancreas to secrete
nin (CCK) NaHCO3 & enzymes, increases
intestinal motility

Gastric K cells Stimulates insulin secretion from

Inhibitory endocrine pancreas & inhibit gastric
Peptide (GIP) secretion and motility
 Possible biochemical causes of
digestive disorders
Digestive disorders can arise as a result of:

(1) Enzyme deficiency, eg, lactase and sucrase;

(2) Malabsorption, e.g, of glucose and galactose as a

result of defects in the Na+-glucose cotransporter
(SGLT 1);

(3) Absorption of unhydrolyzed polypeptides leading to

immune responses, e.g, as in Celiac disease; and

(4) Precipitation of cholesterol from bile as gallstones.

Digestion and Absorption of
Carbohydrates
 Dietary Carbohydrates
• Constitute about 40-50% of the calories of average diet
• Can be of two types:
a. Non-digestible carbohydrates e.g. Cellulose
b. Digestible carbohydrates e.g. sugar, starch, glycogen
Disaccharides Polysaccharides
Digestion of Carbohydrate

Starch
α -1, 4
Digestion of Carbohydrate
 Clinical Correlation

• Serum amylase and lipase are elevated in cases

of pancreatitis

• Acarbose, an α-glucosidase inhibitor, treatment

of DM.
 Digestion of cellulose

• Cellulose contains β(1-4) bonds between glucose

molecules.
• In humans, there is no β (1-4) glucosidase that can digest
such bonds. So cellulose passes as such in stool.
• Cellulose helps water retention during the passage of
food along the intestine  producing larger and softer
feces  preventing constipation.
 Glucose Transporters
Types Tissue locations Functions
A. Facilitative bidirectional transporters
GLUT 1 Brain, kidney, colon, placenta, Glucose uptake
RBCs
GLUT2 Liver, pancreas, small intestine, Rapid uptake or release of
kidney glucose
GLUT3 Brain, kidney, placenta Glucose uptake
GLUT4 Heart & skeletal muscle, Insulin-stimulated glucose
adipose tissue uptake
GLUT5 Small intestine Absorption of glucose,
fructose and galactose
B. Na-dependent unidirectional transporter
SGLT-1 Small intestine and kidney Active uptake of glucose
against concentration gradient
 Absorption of digested
carbohydrates
• Glucose & galactose are
absorbed by the same
SGLT-1 from the
intestinal lumen
• Other monosaccharides
are absorbed by carrier-
mediated diffusion via
GLUT 5
• Monosaccharides are
then released into the
blood through GLUT2
• Both GLUT2 and GLUT5
are insulin insensitive
 Lactose Intolerance
• Prevalence: Most common
among adults of African or
Asian descent
• Cause: A genetic defect
resulting decreased amount
of lactase
• Symptoms: Bloating,
diarrhea and dehydration
• Diagnosis: Oral tolerance
test and measurement of H2
gas in the breath
• Treatment: less intake of
milk, use of lactase-treated
products; or intake of
lactase pills prior to eating.
Digestion and Absorption of
Proteins
 Introduction
• Most of the dietary N2 is consumed in the form of
protein
• An average diet may contain 70–100 g of proteins
• Proteins are generally too large to be absorbed

• They must, therefore, be hydrolyzed to yield their

constituent amino acids, which can be absorbed.
• Proteases are produced by three different organs of
GIT: stomach, pancreas, and small intestine
 Proteases
• Enzymes that hydrolyses peptide bonds of proteins

Proteases

• Many are synthesized as larger, inactive forms known as

zymogens
• Are of two main types:
• Endopeptidases: cleave peptide bonds within protein
chains
• Exopeptidases: cleave one amino acid progressively
from the C-or N-terminal end of the peptide
Examples of Endopeptidases
 Examples of Exopeptidases
Can be of two subtypes:
• Carboxypeptidases: release amino acids from
the free carboxyl terminal e.g.

• Aminopeptidases: cleave one amino acid at a time

from the N terminus of peptides
 Why Zymogens?
• Proteases and phospholipases (but not lipases and
glycosidases) are dangerous digestive enzymes.

• Must be kept chained and muzzled until they reach the

GIT lumen

• Otherwise they attack proteins and membrane lipids in

the cells of their birth and cause auto-digestion.

• This is always prevented by synthesizing them in

inactive form (zymogens)
Activation of the gastric and pancreatic
zymogens
 Digestion of Proteins
• Mouth: No protein digestion

• Stomach: Begins in the stomach

& completes in the intestine

• Gastric HCl denatures proteins &

pepsin hydrolyses them into
peptide fragments and free AAs.

• Pepsin hydrolysis contributes

about 10-15% of dietary proteins
but not essential for survival
 Digestion of Proteins
• Small intestine: Further digestion
in intestine is carried out by
pancreatic proteases

• HCO3- maintains opt. alkaline pH

for proteases

• Amino-, di- & tri-peptidase

secreted from/present inside the
epithelial cells complete the last
step of digestion

• Free AAs are then absorbed and

transported by portal circulation
 Clinical Correlation
Nontropical sprue (adult celiac disease)
• A general malabsorptive disorder due to consumption
of gluten containing foods (wheat, rye and barley)
• Cause: Contain toxic protein called gliadin which
produce antibodies to endomysium of smooth muscle
and causes damage to the small intestine
• High-risk populations: Patients with Down's
syndrome, type 1 DM, lupus and rheumatoid arthritis
• Diagnosis: Intestinal biopsy and serological testing for
antigliadin and antiendomysial antibodies
• Treatment: Life-long complete abstinence from gluten-
containing food
 Clinical Correlation
Achlorhydria
• lack of ability to produce HCl (due to autoimmune
destruction of gastric parietal cells)
• Deficiencies in protein digestion and absorption
Peptic Ulcer
• Bicarbonate is released from the pancreas in
response to the hormone secretin
• Failure to fully neutralize the acidic gastric contents
results in peptic ulcers in the duodenum.
Absorption of Amino acids
and Small peptides Lumen of small intestine
Small H+ +
Na+ peptides H /peptide
Amino acids symport
• Absorbed by two Na+/aa
mucosal symport
different mechanisms cell Na+ H+

Small
a. Na+ & H+ dependent Amino acids peptides
symport systems for Aminopeptidase
Di- and tripeptidases
AAs & small peptides Na+
K+
amino acid
b. Facilitated diffusion for carriers
(facil. diffusion) Na+,K+
the release of absorbed ATPase
K+
AAs into the blood Amino acids Na +
pump
18 Interstitial fluid Blood
 Disorders of Protein
digestion & absorption

 Hartnup disease (Neutral

amino aciduria)

 Cystinuria
Digestion and absorption of
Lipids
 Lipid Digestion and Absorption
• A heterogeneous group of hydrophobic org. molecules
• Provides maximum amount of energy for the body
• Average adult daily intake is about 30-50g
• Dieatary lipids consist of mainly TGs (>90%) and other
lipids (<10%) e.g. cholesterol, cholesteryl esters,
phospholipids, and free FAs.
• Normally, 95% of ingested lipids are digested and
absorbed
• Digestion (hydrolysis) is only partial and requires the
presence of bile acids/salts
 Enzymes involved in lipid digestion
Lipase: Hydrolyses ester bonds of TG
Triacylglycerol + 2H2O 2-Monoacylaglycerol + 2 FA
Lingual : -Contributes very less to fat digestion & acid stable
-Active in small intestine if no HCO3- is secreted
Gastric : -Hydrolyses TGs with short & medium-chain FAs
-May also hydrolyse about 10-30% TGs with long
chain FAs
Pancreatic -Responsible for the majority of digestive action
-Uses a cofactor colipase-bound both to lipase &
micelle surface
-Colipase reduces the surface tension at the lipid-
aqueous interface
 Enzymes involved in lipid digestion
Phospholipase A2
Phosphatidylcholine + H2O 2-lysophosphatidylcholine + FA
• Secreted by pancreas in active proenzyme (zymogen)
• Activated by trypsin
• Partially hydrolyzes both dietary phospholipids and
hepatobiliary phosphatidylcholine
• Specific for FAs in 2-position of phospholipids
Cholesteryl esterase
Cholesteryl ester + H2O Cholesterol + FA
• Secreted by pancreas
• Hydrolyses cholesteryl esters with long chain FAs
 Mixed Micelle
• Bile salts form micelles
• Mixed micelles formed in the
gut contains dietary lipids
and bile salts
• Bile salts form the edge
whereas lipids exist in a
bilayer on the inside of the
micelle
• Provide a large surface area
for the action of pancreatic
lipase
• Also facilitates the
absorption of digested lipid
by gut enterocytes
Digestion of Lipids
 Clinical Correlation
Orlistat:
– an anti-obesity drug that inhibits pancreatic &
gastric lipase
– blocks about 30% of dietary fat from digestion and
absorption
– leads to reduction in body weight in some patients
Olestra:
– an artificial fat composed of a sucrose polyester &
fatty acids
– not degraded by gastric or pancreatic lipases
– passes through undigested and unabsorbed
– excess use may interfere with absorption of fat-
soluble vitamins
Absorption of lipids

• Products of lipid digestion

are solubilized and
converted into small mixed
micelles by bile salts

• These micelles diffuse from

the intestinal lumen
towards cytosol of the
mucosal cells for their
absorption.
Formation & secretion of chylomicrons

Lymph
 Disorder of Lipid Digestion and
Absorption
Steatorrhea
• Results due to Impaired functioning of any of the
components of lipid digestion and absorption

• Leads to excretion of fat in foul-smelling, bulky

stools, and poor absorption of fat-soluble vitamins.

• Can occur due to three major reasons:

– Impaired hydrolysis of TG

– Insufficent secretion of bile

– Impaired absorption by the intestinal mucosa

 Abnormalities of Lipid Digestion due
to Impaired Lipolysis
Type of Defect Biochemical Disturbances Disease States (e.g.)

Rapid gastric Reduction in the efficiency Gastrectomy, as in

emptying of lipid interaction with treatment of ulcer
bile & pancreatic or neoplasm of
secretions stomach
Acidic Inactivation of pancreatic Zollinger-Ellison
duodenal pH lipase & decreased syndrome
ionization of bile acids
Decreased Deficiency of bile & Disorders associated
CCK released pancreatic secretions with mucosal
destruction, regional
enteritis, Hartnup
disease
 Abnormalities of Lipid Digestion due
to Impaired Lipolysis
Type of Defect Biochemical Disturbances Disease States (e.g)

Congenital Defective lipolysis

lipase or
colipase
deficiency
Pancreatic Defective lipolysis Chronic pancreatitis,
insufficency Pancreatic duct
obstruction (e.g.
cystic fibrosis)
Absent or Decreased lipolysis due Severe parenchymal
decreased bile to impiared micelle liver diseases
salts formation
Thank You