CONTENTS Digestion of carbohydrates Absorption of carbohydrates Clinical

CONTENTS Digestion of carbohydrates Absorption of carbohydrates Clinical significance

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

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

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.

Action of ptylin (salivary amylase) • Location: mouth • It is α-amylase and requires Cl− ion for activation with an optimum p. H 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 p. H falls to 3. 0

Starch, Glycogen and dextrins (Large polysaccharide molecules) (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.

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. HCl Sucrose Fructose + Glucose

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 (amylopsin) to salivary amylase.

Action of pancreatic amylase It is an α- Amylase Optimum p. H=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 p. H of action. Both the enzymes require Chloride ions for their actions (Ion activated enzymes).

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.

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 : 1) Maltase, 2) Sucrase-Isomaltase (a bifunctional enzyme catalyzing hydrolysis of sucrose and isomaltose) 3) Lactase

Reactions catalyzed by Disaccharidases Maltase • Maltose Glucose + Glucose Sucrase Isomaltase • Sucrose Isomaltose 3 Glucose + fructose Lactase • Lactose Glucose + Galactose

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

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.

Baby with Lactose Intolerance

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.

Adult with lactose intolerance

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.

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 CO 2 , H 2 , 2 carbon compounds and 3 carbon compounds or it may remain undigested.

• CO 2 and H 2 causes Distensions and flatulence • Lactose + 2 C + 3 C are osmotically active. • They withdraw H 2 O from intestinal mucosal cell and cause osmotic diarrhea or constipation because of undigested bulk. Abdominal distension Flatulence

Diagnosis • Two tests are commonly used: • Hydrogen Breath Test • The person drinks a lactoseloaded 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.

• 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.

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.

• 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.

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.

DIGESTION OF PROTEINS

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

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

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: q. Secreted by dorsal surface of tongue q. Active at low p. H (p. H 2. 0 – 7. 5) qoptimum p. H 4. 0 -4. 5 q. Ideal substrate-Short chain TGS. q. Milk fat contains short chain fatty acids which are esterified at -3 position, thus it is the best substrate for lingual lipase q. Enzymatic action continues in stomach q. Short chain fatty acids, released are absorbed directly from the stomach wall and enter the portal vein.

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

Digestion in Stomach q Gastric Lipase- secreted in small quantities q More effective at alkaline p. H (Average p. H 7. 8) q Requires the presence of Ca++ q Less effective in stomach due to acidic p. H except when intestinal contents are regurgitated into the gastric lumen q Not effective for long chain fatty acids, most effective for short and medium chain fatty acids q Milk, egg yolk and fats containing short chain fatty acids are suitable substrates for its action

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

Significance of Lingual and Gastric Lipases q Play important role in lipid digestion in neonates since milk is the main source of energy q Important digestive enzymes in pancreatic insufficiency such as Cystic fibrosis or other pancreatic disorders q 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

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

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

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

Contents of Pancreatic Juice q Pancreatic Lipase- For the digestion of triglycerides q Phospholipase A 2 - for the digestion of Phospholipids q Cholesterol esterase-For the digestion of Cholesteryl esters

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

Bile Salts q Bile salts are synthesized in the liver and stored in the gall bladder q They are derivatives of cholesterol q 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

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

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

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

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.

• 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.

Enterohepatic circulation of Bile salts

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.

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

Triacyl glycerol degradation by pancreatic lipase

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

Emulsification and Digestion of Triglycerides

Significance of Pancreatic lipase q. 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. q Orlistat, an antiobesity drug inhibits , gastric and pancreatic lipases, there by decreasing fat digestion and absorption resulting in weight loss.

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

Cholesteryl ester degradation

Phospholipid degradation q The enzyme – Phospholipase A 2 requires bile salts for optimum activity. q Removes one fatty acid from carbon 2 of Phospholipid to form lysophospholipid. q 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.

Phospholipid degradation

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