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A. Digestion

Generally, proteins must be digested into small polypeptides before being absorbed.

Enzymes responsible for protein digestion

  1. Gastric enzyme : viz pepsins
    1. The pepsin precursors are pepsinogens. Pepsinogens are converted into pepsins by gastric HCl. Pepsinogens are ssecreted by the chief cells of the stomach.
    2. Pepsins break peptide bonds adjacent to aromatic amino acids (e.g. next to phenylalanine, tyrosine); their break down products are polypeptides of different sizes.
    3. Importance of protein digestion in stomach :
    4. Although only 10-15% of the protein digestion occurs in stomach, these protein digestion products act as secretogogues; these secretogogues stimulate secretion of proteases by the pancreas. 
  2. Pancreatic and intestinal enzymes
    The pancreatic and intestinal enzymes involved in protein digestion are shown below; the table also shows the site of break down of the peptide bonds by these enzymes:


Site of break down of peptide bonds

Pancreatic enzymes

i.    Trypsin

Carboxyl side of basic amino acids (arginine or lysine)

ii.     Chymotrypsins

Carboxyl side of aromatic amino acids

iii.     Elastase

Carboxyl side of aliphatic amino acids

iv.     Carboxypeptidase A

Carboxyl terminal amino acids that have aromatic or branched aliphatic side


 v.     Carboxypeptidase B

Carboxyl terminal amino acids that have basic side chains

Intestinal brush border enzymes

 i. Aminopeptidases

Amino terminal amino acid

 ii. Carboxypeptidases

Carboxy terminal amino acid

 iii. Endopeptidases

Midportion of peptide molecules

 iv. Dipeptidases

Two amino acids


The pancreatic protein digestion enzymes mentioned above exist as their inactive precursors :

Inactive precursor

Active enzyme







Procarboxypeptidase A

Carboxypeptidase A

Procarboxypeptidase B

Carboxypeptidase B


B. Activators :               

  1. Trypsinogen is converted into trypsin by enteropeptidase (previously called enterokinase)
  2. Trypsin in turn converts :
    1. More trypsinogen into trypsin (autocatalysis)
    2. The other inactive precursors mentioned above into their active form 

C. Endo- and exopeptidases

  1. Endopeptidases
    Trypsin, chymotrypsins and elastase are called endopeptidases; this is because they break the interior peptide bonds in the peptide molecules.
  2. Exopeptidases
    The carboxypeptidases and aminopeptidases are called exopeptidases; this is because they break the terminal amino acids.

D. Absorption


From lumen to enterocyte

  1. For amino acids
    1. Na+ - amino acid secondary active transport
    2. Na+ Cl- - amino acid secondary active transport
    3. Na+ - independent transport of amino acid
  2. For di-and tripeptides
    H – dependent transport mechanism 
  3. Proteins
    1. Although polypeptides with greater than 3 peptides are poorly absorbed, some proteins can still be absorbed, especially in infants. For instance, the secretory immunoglobulins (IgAs) in the maternal colustrum are absorbed by endocytosis from the intestine and then into circulation by exocytosis. Protein absorption decreases with age
    2. but still it persists in adults. Absorption of certain food protein antigens from the intestine can cause allergy.
    3. Absorption of protein antigens (especially bacterial/viral proteins) occurs in M or microfold cells; M cells are
    4. specialized intestinal epithelial cells that overlie the Peyer’s patches (Peyer’s patches are aggregates of lymphoid tissue in the intestine)                            

a. Secretory immunity

Antigen from the M cells go to lymphoid cells and activate the lymphoblasts these enter the circulation and reach the intestinal mucosa and other epithelia. Now, if these lymphoblasts are exposed again to the same antigen, IgA is secreted.


b. Protein in stools

All the ingested protein is absorbed (95 to 97 % in the small intestine and the remaining 2 to 5 % is digested by bacterial action in colon and then absorbed). Thus, there is no ingested protein in stool. The protein in stool is thus derived from :

  1. bacteria within the colon
  2. cellular debris          

Absorption from the enterocyte to interstitium

The amino acids and peptides are transported across the basolateral membrane of the enterocytes by facilitated diffusion or by simple diffusion. They they enter the capillaries of the villus by simple diffusion




Absorption of amino acids is rapid in duodenum/jejunum but slow in ileum.

Source of proteins

  1. Exogenous (or dietary) proteins : 50%
  2. Endogenous proteins : 50%
    1. From secretory proteins in digestive juices (25% )
    2. From desquamated cells    (25% )

Is protein absorption from intestine regulated

Unlike absorption of carbohydrate, absorption of proteins from the intestine seems to be regulated. For example, in starvation ( or if the intestine is partly resected), the brush border enzyme activity increases. 


F. Nucleic Acids

  1. Nucleic acids are digested by the pancreatic nucleases (viz. ribonuclease and deoxyribonuclease) into nucleotides. The nucleotides are further split into nucleosides and phosphoric acid by intestinal enzymes. In turn, nucleosides are split into their sugars and purine/pyrimidine bases. The purine/pyridmidine bases are absorbed by active transport.

G. Fats and lipids

  1. Digestion
    Fat digestion starts primarily in the duodenum. Digestion is by lipase; lipase comes from three sources
    1. Lingual lipase
      This is secreted by Ebner’s glands present on the dorsal surface of the tongue; lingual lipase can digest upto 30% of the dietary triglycerides. Lingual lipase acts on triglycerides to give fatty acids and 1,2 – diacylglycerols.
    2. Pancreatic lipase This is the most important enzyme for lipid digestion; it acts on triglycerides to give fatty acids and monoglycerides. 

H. Gastric lipase

This is not important in humans except in pancreatic insufficiency; it acts on triglycerides to give fatty acids and glycerol.

  1. Pancreatic lipase
    Types of pancreatic lipase
    1. Colipase-activated pancreatic lipase
      Colipase is a pancreatic enzyme; it activates pancreatic lipase. Colipase itself is secreted as procolipase; trypsin activates procolipase to colipase.    
      This type of pancreatic lipase can only split triglycerides.
    2. Bile salt-activated pancreatic lipase
      This is less active (about 10 to 60 times) than colipase-activated pancreatic lipase. However, it can split triglycerides, cholesterol esters, esters of fat-soluble vitamins and phospholipids. 
  2. Action
    Pancreatic lipase splits the fatty acids in position 1 and 3 of the triglycerides but not the fatty acid in position 2.

Thus, it splits triglycerides into 2 fatty acids and 2-monoglyceride.


I. Emulsification :

  1. Meaning :
    The process of break down of fat into small fat droplets (less than 1 micrometer in diameter) is called emulsification.  
  2. Carried out by :
    Bile salts, lecithin and monoglycerides. 
  3. Importance :
    Fats must first be emulsified before pancreatic lipase can act on them. Other pancreatic enzymes for fat digestion 
  4. Cholesteryl ester hydrolase :
    This acts on dietary cholesteryl esters and splits it into cholesterol. 
  5. Phospholipase A2
    1. This exists as pro-phospholipase A2; it gets activated by trypsin into phospholipase A2. It acts on phospholipids to liberate fatty acids and lysophospholipids.
    2. End products of fat digestion in the intestinal lumen
    3. Fatty acids, monoglycerides, cholesterol and lysophospholipids. 

J. Micelle formation

  1. What is a micelle
    A micelle (approx. 5 nm in diameter) is a spherical aggregate consisting of 2 ‘parts’  
  2. A central lipid phase (hydrophobic) :
    1. The center of the micelle has digested end products of fat (viz. fatty acids, monoglycerides, cholesterol, lysophospholipids); it also has the fat-soluble vitamins.
    2. The fat products have their hydrophobic chains facing the interior and their polar ends facing the water phase outside. 
  3. A peripheral water phase (hydrophilic):
    1. The center is surrounded by a peripheral water phase consisting of bile salts.
    2. (Thus, micelle is formed by digested end products of fat in the center and bile salts in the periphery).
    3. Importance of micelle formation
    4. There is a water layer called the unstirred water (USW) layer in between the intestinal lumen and the intestinal cell. Since fats do not dissolve in water, micelle formation helps in passing through the USW layer to reach the enterocyte. This is because the fat products are kept in the center of the micelle and the water-soluble bile salt is in the periphery.
    5. The micelle moves down its concentration gradient to reach the surface of the enterocyte; here, the fat products are released from the micelle. Since the fat products are released close to the cell membrane, they can diffuse into the cell.
    6. The bile salt is released into the lumen; here, it helps in forming more micelle formation. Finally, the bile salt is absorbed only in the terminal ileum by a sodium-dependent active transport and thus re-used.
    7. The rate-limiting step in lipid absorption is the migration of micelles from the intestinal lumen to the intestinal cell surface. 

K. Absorption

  1. For the end products of fat digestion to cross the unstirred water layer, they must first be made soluble in water; this is done by micelle formation with the help of bile salts (see above)
  2. Micelles help in crossing the unstirred water layer to reach the cell surface; here, micelles break into :
  3. Digested lipid end products.
  4. Bile salts 

1. Lipid end products

a. Site :

Almost all the digested lipids are totally absorbed by the time the chyme reaches the mid-jejunum; most of the absorption occurs in the duodenum.. Lipids enter the enterocyte by passive diffusion.


2. Bile salts

a. Site :

i. Bile salt absorption does not occur much in the jejunum. It remains in the intestinal lumen (this is an advantage because here it helps in forming new micelles) till it reaches the terminal ileum; absorption occurs in the terminal ileum by a sodium-dependent active transport.

Fat in stools

  1. Normally, almost all (95%)of the ingested lipid is absorbed; thus, fat present in the stool is mostly derived from the intestinal flora.
  2. Fate of the digested end products of lipid in the enterocyte
  3. Once inside the enterocyte, the digested lipids enter the smooth endoplasmic reticulum (SER) where they are re-constituted. Only fatty acids with less than 10-12 carbon atoms pass from the mucosal cell directly into the portal blood where they are transported as free (unesterified) fatty acids. 

3. Reconstitution in SER

a. fatty acids (with more than 12 carbon atoms) : are re-esterified to triglycerides.



2-monoglyceride ----------------------- 1-2 diglyceride

Fatty acid



1-2 diglyceride ------------------------------→ 1-2, 3 triglyceride

Fatty acid



MGT : monoacyl glycerol acyl transferase

DGT : diacylglycerol acyl transferase


b.  Cholesterol   -------------------- cholesteryl ester


                                     fatty acids

c. lysophospholipids -------------- phospholipids

Note :

Some of the triglycerides in the cell is formed from glycerophosphate (which is a product of glucose metabolism); this occurs in rough endoplasmic reticulum (RER).


Glucose ---- glycerophosphate---------------          triglycerides

The reconstitution inside the enterocyte helps in maintaining the concentration gradient for diffusion from lumen to cell.



L. Formation :

Site : enterocyte

How formed :

  1. The reconstituted triglycerides and cholesteryl esters coalesce within the SER to from small lipid droplets (approx. 1mm diameter).
  2. They are then coated with a layer of proteins (beta lipoproteins) and phospholipids to form chylomicrons.
  3. The chylomicrons formed in RER move to Golgi apparatus, where carbohydrate moieties are added there. 

M. Transport

The chylomicrons are transported out of the cell by exocytosis.


Importance of beta lipoproteins

Beta lipoproteins (which are synthesized by the enterocyte in the RER) covers the surface of the chylomicrons. In the absence of beta lipoproteins, exocytosis will not occur and the enterocyte becomes engorged with lipids.


Note : The acylation of glycerophosphate and the formation of lipoproteins occurs in the RER

  1. Transport of lipids in circulation
  2. After coming out of the cell, the chylomicrons merge into larger droplets that vary in size from 50 to 500 nm,
  3. depending on the amount of lipids being absorbed. The larger lipid droplets then diffuse into the lacteals, from which they enter the lymphatic circulation.
  4. Long chain and short chain fatty acids
  5. Long chain fatty acids :
  6. Their absorption is greatest in the upper parts of the small intestine; significant absorption also occurs in the ileum.
  7. Short chain fatty acids (SCFA) 

2. What are they

These fatty acids are made up of 2 to 5 carbon chains.

  1. Content
    Their average concentration in lumen is 80 mmol/L.
  2. Consist of
    1. They consist of acetate (60%), propionate (25%) and butyrate (15%). Formation
    2. They are formed by the action of colonic bacteria on dietary fibre.
    3. Dietary fiber is the material that escapes digestion in the upper GIT and enters the colon; it consists of complex
    4. carbohydrates, resisitant starches etc. Colonic bacteria act on dietary fibre to give rise to SCFAs. 

c. Importance/functions of SCFAs

  1. the absorbed SCFAs from colon are metabolized and contribute significantly to the total calorie intake.
  2. The SCFAs are trophic to the colonic epithelial cells
  3. They fight inflammation
  4. Acid-base balance : since a part of the SCFA is absorbed in exchange for hydrogen, it helps in acid-base balance
  5. Helps sodium absorption by an unknown mechanism. 

3. Absorption of cholesterol and other sterols

This occurs in the small intestine. (Sterols of plant origin are poorly absorbed; further, they decrease absorption of cholesterol). The reconstituted cholesterol in the cell is converted into chylomicrons and enters the circulation via the lymphatics.


N. Electrolytes

  1. Sodium transport
    Site : this occurs throughout the small and the large intestine.
    1. diffusion : some sodium diffuses into (or out of) the small intestine, depending on its concentration gradient.
    2. Secondary active transport :
      1. The basolateral membrane of the enterocyte has Na+ - K + ATPase
      2. The luminal membrane has the following secondary active co-transport mechanisms
        SGLT (Sodium-glucose)
        Sodium-amino acid
        Sodium-(di or tri) peptide
        Sodium- chloride  
  2. Chloride transport
    Chloride gets absorbed mostly by passive diffusion down its electrochemical gradient; the electrochemical gradient is established secondary to the active transport of sodium. 
  3. Potassium
    1. Potassium is absorbed from the small intestine; it is secreted into the colon when the luminal potassium
    2. concentration is low. Most of the potassium movement in GIT is due to diffusion.
    3. In the distal colon, there is a H+ - K + - ATPase in the luminal membrane of cells; it moves K+ from lumen into the cell and H+ from cell into the lumen. In spite of the H+ - K + - ATPase in the distal colon, loss of colonic or ileal fluids in chronic diarrhoea can cause severe hypokalaemia.
    4. What happens when dietary K + is high for a long time?
    5. High K + in the diet ----à aldosterone gets secreted --à inserts more Na+ – K + ATPase in the basolateral
    6. membrane of the intestinal cell ---à more K + moves into the cell from the interstitium ---à K + moves out of  the cell into the lumen by passive diffusion --à more K + enters the colon 

O. Important MCQ Tips

  1. Saliva contains 25-30 mEq/L K+ at low flow rate & 15-20 mEq/L at high flow rate
  2. The concentration of K+ in pancreatic juice is same as plasma i.e. around 4.5 mEq/L  
  3. Liver bile contains 5-6 mEq/L whereas Gall Bladder bile has 12 mEq/L
  4. In ileum the concentration rises due to exchange of potassium with Na+ (K+ absorption also occurs). It normally is around 10-12 mEq/L.
  5. As it reaches rectum the conc. of K+ rises to 85 mEq/L  due to colonic secretion of K+.
  6. Normal stool K+ excretion is 5-10 mEq a day  and volume is 100-200 grams.
  7. So max conc. is seen in stool  or in colon  but maximum levels or secretion is seen in saliva  (since volume secreted is 1.5 L/day  as compared to 100-200 ml of stool) 

P. Water

Water movement in the intestine is passive, moving down its osmotic gradient.

  1. Tonicity of chyme in GIT
    1. Duodenum : Hypo- or hypertonic (depending upon the type of food taken)
    2. Rest of the intestine: isotonic. There is an active absorption of electrolytes and nutrients ; this creates an osmotic gradient due to which water moves rapidly, resulting in osmotic equilibrium. Thus, fluid in the intestine is always isotonic to plasma. In other words, there is iso-osmotic reabsorption of electrolytes/nutrients in the intestine.
      Mechanism of action of saline cathartics (e.g. magnesium sulphate) as laxatives :
      Unlike sodium chloride, these salts are poorly absorbed from GIT; thus, .they retain water in the intestine and act as laxatives. 

Q. Mechanism of diarrhoea in cholera Basic facts regarding the enterocyte

  1. the basolateral membrane has Na +– K +– Cl- cotransporter (note : in the renal tubules, Na +– K +– Cl-  is in the luminal membrane)
  2. the luminal membrane has various Cl- channels which are regulated by protein kinases
  3. from the Na +– K +– Cl-  in the basolateral membrane, Cl- enters the cell from the interstitium; from the cell, Cl- enters the lumen by Cl- channels In cholera, one type of Cl- channel in luminal membrane is activated by protein kinase A and therefore by c AMP.

R. Reasons for diarrohoea in cholera :

  1. Increased chloride secretion into the lumen :
    In cholera, the c AMP concentration in the cell is increased (and therefore, many of the chloride channels remain open and chloride moves into the lumen). Although the vibrio cholerae as such stays in the lumen, a part of its toxin moves into the cell and increases the c AMP concentration in the cell. How? This can be explained in the following steps :
    1. the cholera toxin binds to a receptor (called GM-1 ganglioside receptor) on the enterocyte
    2. due to this, an activated subunit of the toxin (called A1 peptide) moves into the cell
    3. this A1 subunit transfers ADP ribose to the alpha-subunit of G s protein; this results in inhibition of the inherent GTPase activity of the Gs protein
    4. thus, once the G s protein is activated, it remains active for a long time (because of inhibition of its inherent GTPase) activity
    5. this causes continuous stimulation of adenylyl cyclase and thus marked increase in intracellular concentration of c AMP
  2. Decreased absorption of sodium from the lumen
    1. This occurs due to increase in c AMP.
    2. Because of the above reasons, there is an increased sodium chloride content in lumen, which results in diarrhoea.
    3. How is ORS (oral rehydration solution) helpful in cholera ?
    4. The cholera toxin does not affect either the Na+-K+-ATPase or the SGLT. Thus, ORS (which contains sodium and glucose and uses the SGLT secondary active cotransport) is effective.

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