BIOCHEMISTRY OF
DIGESTIVE SYSTEM
Syarifah Dewi
Dept. Biochemistry & Molecular Biology
Faculty of Medicine, University of Indonesia
SALIVARY FLUID
Approximately 99% water
Electrolytes: sodium, potassium, calcium,
chloride, magnesium, bicarbonate,
phosphate
Proteins: enzymes, immunoglobulins and
other antimicrobial factors, mucosal
glycoproteins (mucin)
glucose and nitrogenous products, such as
urea and ammonia
Stimulated: 1-3 ml/min, unstimulated: 0.25-
0.35 ml/min
DIGESTION OF CARBOHYDRATE
The largest sources of dietary calories
Digestive enzyme of carbohydrate
1. Salivary and pancreatic α-Amylase in
mouth and duodenum
2. Disaccharidases intestinal brush border
membrane
Α-AMYLASE
Secreted from salivary and pancreas gland
It is an endoglucosidase hydrolizes
internal α-1,4-bonds between glucosyl
residues
Inactivated by the acidity of the stomach
contents
Α-AMYLASE
Salivary α-amylase converts starch to
smaller polysaccharides (α-dextrins)
Pancreatic α-amylase converts α-dextrins
to disaccharides (maltose), trisaccharides
(maltotriose) and oligosaccharides (limit
dextrin)
Pankreatic juice contains bicarbonate
neutralize gastric acid
Action of salivary and pancreatic α-amylase
DISACCHARIDASES
Attached to membrane in the brush border
(microvilli)
Disaccharidases based on glycosidase activities
- glucoamylase: exoglucosidase, α-1,4-bonds
- the sucrase-isomaltase complex: hydrolayze
sucrose (α-1,2-bond), α-1,6-bonds in dextrin
- trehalase: hydrolyze trehalose (α-1,1-bond)
- β-glycosidase complex (lactase-
glucosylceramidase): hydrolyze lactose (β-1,4-
bond), glycolipids
Polysaccharides Disaccharides
ABSORPTION OF CARBOHYDRATE
Na+-dependent transporters (secondary active transport)
Facilitative glucose transporters (depend on its
concentration gradient): GLUT
LACTOSE INTOLERANCE
Refers to a condition of pain, nausea and
flatulence after the ingestion of food
containing lactose (dairy product)
Deficiency of lactase (primary lactase
deficiency)
Intestinal injury (secondary lactase
deficiency)
DIETARY FIBER
It consist of plant materials that are
polysaccharide derrivatives, cannot be digested
by human enzymes in intestinal tract
Soluble fiber: pectins, mucilages, gums
Insoluble fiber: cellulose, hemicellulose, lignins
It is metabolized by bacteria in colon, form gas
(H2, CO2, methane), shortchain fatty acids
(acetic, propionic, butyric acid), lactate
Incomplete products of digestion in the
intestines increase water retention
defecation
DIGESTION OF LIPID
Limited digestion in mouth and
stomach
In the intestine, the fats are emulsified
by bile salts increases the surface
area to digest
Enzyme: pancreatic lipase
Triacylglycerol free fatty acids and
2-monoacylglycerol
DIGESTION OF LIPID
Phospholipids are hydrolyzed by phospholipase A2
Cholesterol esters are hydrolyzed by cholesterol
esterase
ABSORPTION OF LIPID
Fatty acids & 2-monoacylglycerols are packaged
into micelles emulsified by bile salts
The micelles interact with the enterocyte
membrane diffusion into the cell
The bile salts remain in the intestinal lumen
reabsorbed and sent back to the liver
(enterohepatic circulation)
In intestinal epithelial cells resynthesize TG
package with protein, phospholipids and
cholesterol esters into a soluble lipoprotein
particle (chylomicron)
DIGESTION OF PROTEIN
Begins in the stomach and completed in the
intestine
These eznymes are secreted in inactive forms
(zymogen)
In the stomach: pepsinogen is secreted by chief
cells, acctivated by HCl and pepsin
(autocatalytic)
Pepsin: endopeptidase, work at low pH (1-2), it
tends to cleave peptide bonds in which the
carboxyl group in aromatic or acidic amino acid
DIGESTION OF PROTEIN
In the intestine: digestion by pancreatic
proteases and enzymes from intestinal cells
Pancreatic proteases trypsinogen
(trypsin), chymotripsinogen (chymotripsin),
proelastase (elastase), procarboxypeptidase
(carboxypeptidase)
Intestinal cells aminopeptidase
(exopeptidase)
ABSORPTION OF AMINO ACID
Na+-dependent transport protein (mucosal
membrane)
Facilitated transporters (serosal membrane)
DIETARY NUCLEIC ACIDS
Pancreas ribonucleases and
deoxyribonucleases,
phosphodiesterases
Intestinal cells nucleotidase,
nucleosidase
Dietary purin converted to uric
acids in intestinal cells urine
REGULATION OF ENZYMES
SECRETION
Secretion of enzymes is regulated and
coordinated with electrolytes
Regulation of secretion is through
secretagogues that interact with receptors
on the surface of exocrine cells
Organ Secretion Secretagogue
Salivary gland NaCl, amylase Acetylcholine
Stomach HCl, pepsinogen Acetylcholine, histamin, gastrin
Pancreas-acini NaCl, digestive enzymes Acetylcholine, cholecystokinin, secretin
Pancreas-duct NaHCO3, NaCl Secretin
Small intestine NaCl Acetylcholine, serotonin, vasoactive
intestinal peptide (VIP), guanylin
INTESTINAL PUTREFACTION &
FERMENTATION
Food residues large intestine
Bacterial activity produce various gases:
CO2, methane, hydrogen nitrogen, H2S
Intestinal bacteria synthesis of certain
vitamin: vit K, possibly members of B
complex
GASTRIC ACID (HCL)
Secreted by parietal cells, required ATP
Enzyme: carbonic anhydrase
CO2 + H2O HCO3- + H+
Functions: activate pepsinogen pepsin,
denature protein, killing microorganisms
Histamin (ECL cell) potent stimulator of
HCl secretion H2 receptor
THE BILE
Produced by the liver, storage in the gallbaldder
Secrete to duodenum initiated by
cholecystokinin
Composition: water, bile acids, mucin, pigments,
cholesterol, fatty acids, inorganic salts
Functions: emulsification, neutralization of acid,
excretion (drugs, toxin, bile pigment), solubilize
cholesterol
BILE ACIDS
Cholic acid, chenodeoxycholic acid
synthesized in the liver from cholesterol
Enter the bile as glycine or taurine conjugates:
glyco/taurocholic acid, glyco/tauro
chenodeoxycholic acid
Bile contains significant quantities of alkali
cations (Na+, K+) form bile salt
In the intestine, deconjugation and 7α-
dehydroxylation (bacterial activity)
deoxycholic and lithocholic acid
Ileum 95% bile acid will be reabsorbed
(enterohepatic circulation)
Equilibrium bile salt-phospholipid-cholesterol
phase diagram
Cholesterol stone (85%): crystalline
cholesterol monohydrate predominantly
Pigment stone: bilirubin calcium salt
predominantly
- Black pigment: cirrhosis, hemolytic anemia
- Brown pigment: infection
PORPHYRIN METABOLISM
Porphyrin: 4 pyrrole rings are joined by
methenyl bridge (-CH-)
Heme a porphyrin ring coordinated with
an atom of iron (Fe)
Most heme is complexed with protein
hemoglobin, mioglobin, cytochrome
(including CYP450)
Pyrrole ring
Heme structure
Heme Synthesis
Degradation of Heme
XENOBIOTIC METABOLISM
Xenobiotic exposure , such drugs, food additives,
pollutan
Biotrasformation reaction
Main organ: Liver
2 phases: phase 1 (hydroxilation) and phase 2
(conjugation)
Enzyme:monooxygenase/CYP450
Aim: increases water solubility easy to
excretion in urine
Metabolisme xenobiotik
CYP450
THANK YOU