Download Biochemistry of Gastrointestinal Fluid and Enzymes

Biochemistry of Digestive Fluids
and Enzymes
Reference: Ch 25 T. Devlin Textbook of
Biochemistry with clinical correlations 7e
Mohamad Nusier MD. PhD.
1
Secretions of the Gastrointestinal
(GI) Tract
1. Primary
Organs
• Salivary
• Stomach
• Pancreatic
• Intestinal
2. Accessory
Organs
• Teeth
• Tongue
• Gallbladder
• Liver
2
Daily Secretion of Digestive Fluids
Fluid
Volume
(ml/day)
pH
Saliva
Stomach
1000-1200
2000-3000
6.0-7.0
1.0-3.5
Pancreas
1200-2000
8.0-8.3
600-700
7.8
50
2000-3000
8.0-8.9
7.8-8.0
60
7.5-8.0
Bile secretion
Brunner’s gland secretion
Intestinal juice
Large intestine
3
Digestive enzymes are classified into
four groups:
1. Proteolytic Enzyme: split proteins to amino acids
2. Lipolytic Enzyme: split fats to fatty acids and
glycerol
3. Amylolytic Enzyme: split carbohydrate and
starch to simple sugars
4. Nucleolytic Enzyme: split nucleic acids to
nucleotides
4
Mouth enzymes & Functions
1. Ptyalin:
Converts starch to simple soluble sugars
2. Amylase:
Converts starch to soluble sugars
3. Betaine:
Maintains cell fluid balance as osmolytes
4. Bromelain:
Anti-inflammatory agent, tenderizes meat
5
Stomach Enzymes Functions
1. Pepsin: Breaks protein into small peptides
(cuts before Leu, Phe, Trp or Tyr)
2. Gastric amylase: Degradation of starch
3. Gelatinase: Degradation of gelatin and
collagen present as proteoglycans in meat
4. Rennin (Chymosin):
milk to solid particles
5. Gastric lipase:
Conversion of liquid
Degradation of fat
6
Pancreatic Enzymes & Functions
1. Pancreatic lipase:
Degrades triglycerides into fatty acids and
glycerol
2. Phospholipase:
Hydrolyzes phospholipids into fatty acids and
lipophilic substances
3. Trypsin:
Converts proteins to basic amino acids
4. Steapsin:
Breakdown of triglycerides to glycerol and fatty
acids
7
Pancreatic Enzymes & Functions
5. Chymotrypsin: (cuts after Phe, Trp, or Tyr)
Converts proteins to aromatic amino acids
6. Carboxypeptidase: (cleaves a peptide bond at the Cterminal end of a protein)
Degradation of proteins to amino acids
7. Pancreatic amylase:
Degradation of carbohydrates to simple sugars
8. Elastases: (cuts after Ala, Gly, Ser, or Val)
Degrade the protein elastin
9. Nucleases:
Conversion of nucleic acids to nucleotides and
8
nucleosides
Small Intestine Enzymes & Functions
1. Sucrase:
Converts sucrose a disaccharides to
monosaccharides
2. Maltase:
Converts maltose to glucose
3. Lactase:
Converts lactose to glucose and galactose
4. Isomaltase:
Converts maltose to isomaltose
9
10
11
Digestive Process
1. Ingestion- taking food in
•
Bolus- an amount of food passing through tract
2. Propulsion- moves food through tract
•
•
Swallowing- voluntary
Peristalsis- involuntary muscular waves moves food
forward
3. Mechanical digestion- physical chewing, mixing,
churning
•
Segmentation- rhythmic local constrictions of intestine
for mixing
12
Digestive Process, cont’d
4. Chemical digestion- catabolism/ breakdown of
polymers into monomers by enzymes
•
Begins in mouth, essentially complete in small intestine
5. Absorption- passage of digested end products
across wall into blood
•
•
•
Monomers, vitamins, minerals and water
Pass through mucosal cells lining tract
Small intestine major absorption site
6. Defecation- eliminates indigestible substances and
other wastes from body via anus in form of feces
13
Functions of Saliva
1. Maintenance of oral hygiene
•
Lysozyme, peroxidases (XEROSTOMIA)
2. Maintain mineralization of teeth
•
(Ca and pH)
2+
3. Lubrication
•
Speaking and swallowing (mucin)
4. Digestive function
•
Amylase (Ptyalin) & Lipase
5. Solvation
•
Enables one to taste foodstuffs
14
Three Major salivary glands
% Total
Type
1. Submandibular (submaxillary): 70% sero-mucin
2. Parotid:
25% serous (protein)
3. Sublingual:
5% mucin (mucus)
Total volume
1,500 mL/day
15
Salivary Flow Rate
Na
Cl
100
Na
80
80
60
60
40
HCO3
Cl
20
HCO3
K
K
0
1
2
3
Flow rate (mL/min)
40
20
0
4
Plasma
16
Saliva
Ion concentration (mM)
120
100
Ion concentration (mM)
140
Composition of Human Saliva
17
Pancreatic Structure
1. Endocrine cells
• They are arranged in small islets within
the pancreas, secrete directly into the
circulation:
•
•
•
•
Insulin
Glucagon
Somatostatin
Polypeptides
18
Pancreatic Structure, Cont’d
2. Exocrine cells
• They are organized into acini that
produce four types of digestive
enzymes:
•
•
•
•
Peptidases
Lipases
Amylases
Nucleases
19
Pancreatic Structure, Cont’d
3. Ductal cells
• Each day they secrete about 1200-1500 mL
of pancreatic juice containing a high
concentration of HCO3
• The HCO3 neutralizes gastric acid and
regulates the pH of the upper intestine
• Failure to naturalize the chyme as it
enters the intestine will result duodenal
ulcers
20
Pancreatic Juice Composition
21
Pancreatic Secretion
22
Ion Concentration (mM)
pH
8.2
340
pH
7.8
Osm 300
7.4
260
160
Osmolality
Pancreatic Secretion
+
Na
HCO3-
120
80
ClK+
40
0
0
300
100
Secretion rate (mL/hr)
500
23
Functions of Gastric Secretions
1. Digestion of proteins (pepsinogen and
HCl)
2. Protection of stomach (HCO3 and
mucus)
3. Absorption of vitamin B12 (intrinsic
factor)
4. Destroy bacteria and other
microorganisms (HCl)
24
Gastric Juice Composition
25
Gastric Secretions
26
HCl Section Mechanism
1. HCl is secreted into the parietal cell canaliculi
by a three step process:
• Active transport process is begun by transport of
+
lK and Cl into the canaliculi. C is transported by
either a pump or through a channel. The flow of
Cl- creates a –ve potential inside the canaliculi,
causing K+ to flow +vely into the canaliculi
+
+
+
+
• H is exchanged for K by H -K ATPase pump
• Water enters the canaliculi down the osmotic
gradient created by the movement of HCl into the
27
canaliculi
HCl Section Mechanism, Cont’d
+
2. The H entering the canaliculi is supported by
dissociation of carbonic acid (H2CO3) into H+ and
bicarbonate (HCO3 ) within the parietal cell:
•
•
•
H2CO3 is formed from the Rxn catalyzed by carbonic
anyhydrase:
CO2 + H2O →
H2CO3
HCO3 diffuses back into the plasma in exchange for Cl
3. Most the HCl that is secreted into the stomach is
neutralized and reabsorbed within the small
intestine
28
HCl Section Mechanism, Cont’d
4. Active transport process involve in the
generation of HCl, requires a large amount of
ATP generated by mitochondria in parietal
cell
5. The pH of the parietal cell secretion can be as
low as 0.8
+
+
6. The H -K ATPase pump is irreversibly
inhibited by omeprazole (PPI) which is used
for the treatment of duodenal and gastric
ulcers
29
Regulation of Gastric Secretion
1. Cephalic
•
•
•
Food in mouth increases secretion of HCl (efferent
vagus)
Anger and tension increases secretion HCl
Fear and depression increases secretion HCl
2. Gastric
•
•
•
Stimulated by distension (vago-vagal),
hypertonicity
Alcohol and AAs (gastrin)
+
Inhibition by H (-ve feedback, somatostatin)
3. Intestinal
•
Peptides (gastrin), AA’s,)
30
Small Intestine
1. Major digestive organ
2. Longest part of alimentary canal (3-6 hour
journey)
3. Three subdivisions
•
Duodenum
•
•
•
Jejunum
•
•
Shortest but lots going on
Hepatopancreatic ampulla- bile duct and main pancreatic
duct enter
Middle portion
Ileum
•
Last part joins large intestine at ileocecal valve
31
Intestinal Juice
1.
2.
3.
4.
5.
Glands make 1-3 L daily
Stimulated by entrance of acidic chime
Slightly alkaline to neutralize chyme
Largely water with some mucus
Relatively enzyme poor because
enzymes are bound to the brush border
32
Carbohydrate and Protein Digestion
33
Fat and Nucleic Acid Digestion
34
Large Intestine
1. Shorter but larger diameter than
small intestine
2. Major function in feces elimination
and water reabsoprtion
3. 12-24 hours
35
Bacterial Flora
1. Most bacteria killed by stomach acid or
enzymes
2. Some survive or come up from the anus
3. Ferment indigestible carbohydrates (such as
cellulose)
4. Release acids and gases (about 500 mL/day)
5. Also release B complex vitamins and most
of the body’s vitamin K need (for clotting)
36
Bile
• Function of Bile
• Bile is required for the digestion and absorption
of fats and for excretion of water-insoluble
substances as cholesterol and bilirubin
• Formation of Bile
• It is formed from two sites:
• Hepatocytes
• Ductal cells
37
Bile, Cont’d
• Storage of Bile
• Although it is secreted continuously, but
it is stored in the gallbladder during the
inter-digestive period
• Release of Bile
• It is released into the duodenum during
the digestive period
38
Bile Fluid
1. Flows toward bile duct branches in portal triads
2. Constantly made by hepatocytes
3. List of contents but bile salts and phospholipids
important in digestion
4. Bile cholesterol is important because it is one of
the few ways in which cholesterol stores can be
regulated
39
Bile Salts
•
Role of Bile Salts in Emulsifying Fat
1. Break up large globule into smaller globules
2. Makes for large surface area for lipid digesting
enzymes
3. Facilitate fat and cholesterol absorption
• Most of bile (but not bile salts) will leave with
feces
• Bile salts are actually recycled for reuse
Recycling of Bile Salts
1. The total circulating pool of bile salts is about
3.6 g
2. Because 4-8 g of bile salts are required to
digest and absorb a meal (more if the meal is
high in fat), the total pool of bile salts must
circulate twice during the digestion of each
meal
3. The bile salts usually circulate 6-8 times
daily`