1. Digestion of carbohydrates
CONTENTS
Digestion of carbohydrates
Absorption of carbohydrates
Clinical significance

2. Digestion and absorption of carbohydrates
Carbohydrates present in the diet
Disaccharides
Monosaccharides
Polysaccharides
Lactose Maltose Sucrose
Starch Glycogen
Glucose Fructose Pentose
In GIT, all complex carbohydrates are converted to simpler monosaccharide form which is the absorbable form.

3. Details of digestion of carbohydrates
2 Types of enzymes are important for the digestion of carbohydrates
Amylases
Disaccharidases
Convert disaccharides to monosaccharides which are finally absorbed
convert polysaccharides to disaccharides
Maltase
Salivary Amylase
Sucrase-Isomaltase
Pancreatic Amylase
Lactase
Trehalase

4. Digestion in the Mouth
Digestion of Carbohydrate starts in the mouth, upon contact with saliva during mastication. Saliva contains a carbohydrate splitting enzyme called salivary amylase , also known as ptylin.

5. Action of ptylin (salivary amylase)
Location: mouth
It is α-amylase and requires  Cl− ion for activation with an optimum pH of 6.7 (Range 6.6 to 6.8).
The enzyme hydrolyses α-1→ 4 glycosidic linkages deep inside polysaccharide molecules.
However, ptylin action stops in the stomach when the pH falls to 3.0.

6. Starch, Glycogen and dextrins (Large polysaccharide molecules)
α- Amylase
Glucose,Maltose and Maltotriose.
(Smaller molecules)
Drawback
Shorter duration of food in mouth.
Thus it is incomplete digestion of starch or glycogen in the mouth.

7. Digestion in the Stomach
There is no enzyme to break the glycosidic bonds in gastric juice.
However, HCl present in the stomach causes hydrolysis of sucrose to fructose and glucose.
Sucrose Fructose + Glucose
HCl

8. Pancreatic juice contains a carbohydrate splitting enzyme,
Digestion in Duodenum
Food bolus reaches the duodenum from the stomach where it meets the pancreatic juice.
Pancreatic juice contains a carbohydrate splitting enzyme,
pancreatic amylase
(amylopsin) similar
to salivary amylase.

9. Action of pancreatic amylase
It is an α- Amylase
Optimum pH=7.1
Like ptylin, it requires Cl− ion for its activity.
It hydrolyses α-1→ 4 glycosidic linkages situated well inside polysaccharide molecules.
Note: Pancreatic amylase, an isoenzyme of salivary amylase, differs only in the optimum pH of action. Both the enzymes require Chloride ions for their actions (Ion activated enzymes).

10. Reaction catalyzed by pancreatic amylase
Starch/Glycogen
Pancreatic Amylase
Maltose/ Isomaltose
Dextrins and oligosaccharides
Note:
Main digestion takes place in the small intestine by pancreatic amylase. Digestion is completed by pancreatic amylase because food stays for a longer time in the intestine.

11. What are Disaccharidases?
They are present in the brush border epithelium of intestinal mucosal cells where the resultant monosaccharides and others arising from the diet are absorbed.
The different disaccharidases are :
Maltase,
2) Sucrase-Isomaltase (a bifunctional enzyme catalyzing hydrolysis of sucrose and isomaltose)
3) Lactase

12. Reactions catalyzed by Disaccharidases
Maltase
Maltose Glucose + Glucose
Sucrose Isomaltose Glucose + fructose
Lactose Glucose + Galactose
Sucrase Isomaltase
Lactase

13. Clinical significance of Digestion
Lactose intolerance is the inability to digest lactose due to the deficiency of Lactase enzyme.
Causes
Congenital
Acquired during lifetime
Primary
Secondary

14. Congenital Lactose intolerance
It is a congenital disorder
There is complete absence or deficiency of lactase enzyme.
The child develops intolerance to lactose immediately after birth.
It is diagnosed in early infancy.
Milk feed precipitates symptoms.

15. Baby with Lactose Intolerance

16. Primary Lactase deficiency
Primary lactase deficiency develops over time
There is no congenital absence of lactase but the deficiency is precipitated during adulthood.
The gene for lactose is normally expressed up to RNA level but it is not translated to form enzyme.
It is very common in Asian population.
There is intolerance to milk + dairy products.

17. Adult with lactose intolerance

18. Secondary lactase deficiency
It may develop in a person with a healthy small intestine during episodes of acute illness.
This occurs because of mucosal damage or from medications resulting from certain gastrointestinal diseases, including exposure to intestinal parasites such as Giardia lamblia.
In such cases the production of lactase may be permanently disrupted.
A very common cause of temporary lactose intolerance is gastroenteritis, particularly when the gastroenteritis is caused by rotavirus.
 Another form of temporary lactose intolerance is lactose overload in infants. Secondary lactase deficiency also results from injury to the small intestine that occurs with celiac disease, Crohn’s disease, or chemotherapy.
This type of lactase deficiency can occur at any age but is more common in infancy.

19. Clinical manifestations
In the form of abdominal cramps, distensions, diarrhea, constipation, flatulence upon ingestion of milk or dairy products
Biochemical basis
Undigested lactose in intestinal lumen is acted upon by bacteria and is converted to CO2 , H2 , 2 carbon compounds and 3 carbon compounds or it may remain undigested.

20. CO2 and H2 causes Distensions and flatulence
Lactose + 2C + 3C are osmotically active.
They withdraw H2O from intestinal mucosal cell and cause osmotic diarrhea or constipation because of undigested bulk.
Flatulence
Abdominal distension

21. Two tests are commonly used: - Hydrogen Breath Test
Diagnosis
Two tests are commonly used: -
Hydrogen Breath Test
The person drinks a lactose-loaded beverage and then the breath is analyzed at regular intervals to measure the amount of hydrogen. Normally, very little hydrogen is detectable in the breath, but undigested lactose produces high levels of hydrogen. The test takes about 2 to 3 hours.

22. Stool Acidity Test
The stool acidity test is used for infants and young children to measure the amount of acid in the stool. Undigested lactose creates lactic acid and other short chain fatty acids that can be detected in a stool sample. Glucose may also be present in the stool as a result of undigested lactose.
Besides these tests, urine shows- positive test  with Benedict’s test, since lactose is a reducing sugar and a small amount of lactose is absorbed in the intestinal cell by pinocytosis and is rapidly eliminated through kidneys in to urine.(Lactosuria)
Mucosal biopsy confirms the diagnosis.

23. Management of lactose intolerance
Avoidance of dairy products.
Although the body’s ability to produce lactase cannot be changed, the symptoms of lactose intolerance can be managed with dietary changes.
Most people with lactose intolerance can tolerate some amount of lactose in their diet. Gradually introducing small amounts of milk or milk products may help some people adapt to them with fewer symptoms.
Partly digested dairy products can also be given.

24.  Lactose-free, lactose-reduced milk, Soy milk and other products may be recommended. 
Lactase enzyme drops or tablets(Yeast tablets) can also be consumed.
Getting enough calcium is important for people with lactose intolerance when the intake of milk and milk products is limited.
A balanced diet that provides an adequate amount of nutrients—including calcium and vitamin D—and minimizes discomfort is to be planned for the patients of lactose intolerance.

25. Sucrase-Isomaltase deficiency
These 2 enzymes are synthesized on a single polypeptide chain, hence , their deficiencies coexist.
Signs and symptoms
Same as that of lactose intolerance.
Urine does not give +ve test with Benedict’s test because of sucrose(Non reducing sugar).
History confirms the diagnosis.
Most confirmatory test is mucosal biopsy.

26. DIGESTION OF PROTEINS

46. Dietary fat Composition
More than 95% are triglycerides, the other are
Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.

47. Dietary sources of Lipids
Animal Sources
Dairy products- meat, butter, ghee, fish & eggs
Vegetable Sources
Cooking oils- Sun flower oil, Mustard oil, Ground nut oil
Fats from other vegetable sources

48. Digestion in Mouth
Hydrolysis of triacylglycerols is initiated by lingual and gastric lipases, which attack the 3- ester bond forming 1,2-diacylglycerols and free fatty acids, aiding emulsification.
Lingual lipase:
Secreted by dorsal surface of tongue
Active at low pH (pH 2.0 – 7.5)
optimum pH
Ideal substrate-Short chain TGS.
Milk fat contains short chain fatty acids which are esterified at -3 position, thus it is the best substrate for lingual lipase
Enzymatic action continues in stomach
Short chain fatty acids, released are absorbed directly from the stomach wall and enter the portal vein.

49. Triglyceride degradation
Triglycerides are degraded by lipases to form free fatty acids and glycerol

50. Digestion in Stomach Gastric Lipase- secreted in small quantities
More effective at alkaline pH (Average pH 7.8)
Requires the presence of Ca++
Less effective in stomach due to acidic pH except when intestinal contents are regurgitated into the gastric lumen
Not effective for long chain fatty acids, most effective for short and medium chain fatty acids
Milk, egg yolk and fats containing short chain fatty acids are suitable substrates for its action

51. Role of fats in gastric emptying
Fats delay the rate of emptying of stomach
Action is brought about by secretion of
Enterogastrone
Enterogastrone inhibits gastric motility and
retards the discharge of bolus of food from the
stomach.
Thus fats have a high satiety value.

52. Significance of Lingual and Gastric Lipases
Play important role in lipid digestion in neonates since milk is the main source of energy
Important digestive enzymes in pancreatic insufficiency such as Cystic fibrosis or other pancreatic disorders
Lingual and gastric lipases can degrade triglycerides with short and medium chain fatty acids in patients with pancreatic disorders despite a near or complete absence of pancreatic lipase

53. Emulsification and digestion
Lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract. 
The digestive enzyme, lipase, is water soluble and can only work at the surface of fat globules. 
Digestion is greatly aided by emulsification, the breaking up of fat globules into much smaller emulsion droplets.

54. Emulsification and digestion
Triacylglycerol digestion occurs at lipid-water
interfaces
Rate of TAG digestion depends on surface area of
this interface which is increased by churning
peristaltic movements of the intestine ,
Combined with the emulsifying action of bile salts
The critical process of emulsification takes place
in the duodenum.

55. Digestion in small intestine
Major site of fat digestion
Effective digestion due to the presence of
Pancreatic lipase and bile salts.
Bile salts act as effective emulsifying agents for
fats
Secretion of pancreatic juice is stimulated by-
Passage of acid gastric contents in to the duodenum
By secretion of Secretin, Cholecystokinin and Pancreozymin, the gastro intestinal hormones.

56. Contents of Pancreatic Juice
Pancreatic Lipase- For the digestion of
triglycerides
Phospholipase A2- for the digestion of
Phospholipids
Cholesterol esterase-For the digestion of
Cholesteryl esters

57. Bile Salts Bile salts are required for the proper functioning of
the pancreatic lipase enzyme
Bile salts help in combination of lipase with two
molecules of a small protein called as Colipase. This
combination enhances the lipase activity.
Bile salts also help in the emulsification of fats
TG particle
Colipase
lipase

58. Bile Salts
Bile salts are synthesized in the liver and stored in the gall bladder
They are derivatives of cholesterol
They consist of a sterol ring structure with a side chain to which a molecule of glycine or Taurine is covalently attached by an amide linkage

59. Bile Salts Bile salts are formed from bile acids
The primary bile acids are cholic acid (found in the largest amount) and chenodeoxycholic acid .
The primary bile acids enter the bile as glycine or taurine conjugates.
In the alkaline bile, the bile acids and their conjugates are assumed to be in a salt form—hence the term "bile salts.“

60. Synthesis of bile salts
In humans, the ratio of the glycine to the taurine conjugates is normally 3:1.

61. Bile Salts
A portion of the primary bile acids in the intestine is subjected to further changes by the activity of the intestinal bacteria.
These include deconjugation and 7-alpha dehydroxylation, which produce the secondary bile acids, deoxycholic acid and lithocholic acid.

62. Enterohepatic circulation of Bile salts
The bile salts present in the body are not sufficient to fully process the fats in a typical meal, thus they need to be recycled.
This is achieved by the enterohepatic circulation.
Specific transporters in the terminal ileum move bile salts from the lumen of the digestive tract to the intestinal capillaries.

63. They are then transported directly to the liver via the hepatic portal vein.
Hepatocytes take up bile salts from the blood, and increase the secretion of bile salts into the bile canaliculi, small passage ways that convey bile into the larger bile ducts.
95% of the bile that is released to the small intestine is recycled via the enterohepatic circulation, while 5% of the bile salts are lost in the feces.

64. Enterohepatic circulation of Bile salts

65. Emulsification by bile salts
Bile salts as emulsifying agents interact with the dietary lipid particles and the aqueous duodenal contents, thereby stabilizing the lipid particles as they become smaller, and preventing them from coalescing.

66. Triacyl glycerol degradation by pancreatic lipase
Pancreatic lipase is specific for the hydrolysis of primary ester linkages(Fatty acids present at position 1 and 3)
It can not hydrolyze the ester linkages of position -2
Digestion of Triglycerides proceeds by removal of a terminal fatty acid to produce an α,β diglyceride.
The other terminal fatty acid is then removed to produce β mono glyceride.

67. Triacyl glycerol degradation by pancreatic lipase

68. Triacyl glycerol degradation by pancreatic lipase
The last fatty acid is linked by secondary ester group, hence can not be hydrolyzed by pancreatic lipase.
β- Mono acyl glycerol can be converted to α- Mono acyl glycerol by isomerase enzyme and then hydrolyzed by Pancreatic lipase.
The primary product of hydrolysis are β- Mono acyl glycerol (78%), α- Mono acyl glycerol (6%) with free fatty acids and glycerol (14%)

69. Emulsification and Digestion of Triglycerides

70. Significance of Pancreatic lipase
The enzyme is present in high concentration in pancreas. Only very severe pancreatic deficiency such as cystic fibrosis results in malabsorption of fats due to impaired digestion.
Orlistat, an antiobesity drug inhibits , gastric and pancreatic lipases, there by decreasing fat digestion and absorption resulting in weight loss.

71. Cholesteryl ester degradation
Dietary cholesterol is mainly present in the
free (Non esterified) form
Only 10-15% is present in the esterified form
Cholesteryl esters are hydrolyzed by pancreatic Cholesteryl esterase (Cholesterol ester Hydrolase) to produce cholesterol and free fatty acid
The enzymatic activity is greatly increased in the presence of bile salts.

72. Cholesteryl ester degradation

73. Phospholipid degradation
The enzyme – Phospholipase A 2 requires bile salts for optimum activity.
Removes one fatty acid from carbon 2 of Phospholipid to form lysophospholipid.
The remaining fatty acid at position 1 can be removed by lysophospholipase , leaving a glycerylphosphoryl base that may be excreted in the feces, further degraded or absorbed.

74. Phospholipid degradation

75. END