Digestion and absorption of carbohydrates

Digestion and absorption of carbohydrates; uptake of glucose in the peripheral cells with detailed clinical significance

1. Student’s Corner Selected for publication Biochemistry For Medics www.namrata.co

2. Topic : Digestion and Absorption of carbohydrates with clinical significance . Presented by : THOSADU RAMDU Pooja . Roll no. : 102.

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

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

5. digestion of carbohydrates

6. 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 .

7. 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 .

8. Starch, Glycogen and dextrins (Large polysaccharide molecules ) α - Amylase Glucose,Maltose and Maltotriose . (Smaller molecules)

9. Shorter duration of food in mouth. Thus it is incomplete digestion of starch or glycogen in the mouth

10. 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

11. 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.

12. 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).

13. Reaction catalyzed by pancreatic amylase Starch/Glycogen Maltose/ Isomaltose + Dextrins and oligosaccharides Pancreatic Amylase

14. 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.

15. 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

16. Maltose Glucose + Glucose Sucrose Isomaltose 3Glucose + fructose Lactose Glucose + Galactose Maltase Sucrase Isomaltase Lactase

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

18. It is a congenital disorder T here 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.

19. Baby with Lactose Intolerance

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

21. Adult with lactose intolerance

22. 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.

23.   Intestinal parasite Rotavirus ( Giardia lamblia )

24. 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.

25. CO 2 and H 2 causes Distensions and flatulence Lactose + 2C + 3C 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

26. 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.

27. 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.

28. 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.

29.   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.

30. 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.

31. 3 mechanisms Passive diffusion Facilitated diffusion/Carrier mediated Active transport

32. Features Passive diffusion Facilitated diffusion Active transport Concentration gradient Down the concentration gradient from high to low. Down the concentration gradient f rom high to low. Against a concentration gradient from low to high Energy expenditure none none Energy expenditure is in the form of ATP Carrier protein/ transporter Not required required required Speed Slowest mode Fast Fastest mode Note: Glucose is a polar molecule. It cannot pass through lipid bilayer of cell.

33. Glucose transporters Na + dependent transporter Na + independent transporter 2 types SGLT GLUT Also called Also called

34. Type of co-transport 2 binding sites on the transporter, one for Na + and other for glucose. Na + binding is important because after Na + binding, conformational changes occurs so that glucose can bind. Na + is transported across cell membrane, down the concentration gradient and glucose goes against a concentration gradient. ATP is spent at the level of Na-K ATPase pump to expel Na out. Both glucose and galactose are absorbed by a sodium-dependent process. They are carried by the same transport protein (SGLT 1), and compete with each other for intestinal absorption.

35. Figure- Showing the co transport of Glucose, mediated by SGLT-1/2. SGLT-1 are  present on the intestinal cells while SGLT-2 are  present on the proximal renal tubular cells.

36. Na + is osmotically active, causes osmotic flow to cells, leading to osmolysis. Na + concentration has to be kept minimal to maintain the downward gradient. Na + is inhibitory to many enzyme actions.

37. Energy released is captured for transport of glucose against a conc. Gradient. Energy is consumed at the level of ATP Solvent drag absorption

38. In deficiency of SGLT- 1, glucose is left unabsorbed and is excreted in feces. Galactose is also malabsorbed . In deficiency of SGLT- 2, the filtered glucose is not reabsorbed back, it is lost in urine, causing glycosuria .

39. Solvent drag is not the main mechanism of glucose absorption but is important after a carbohydrate rich diet. Absorption of galactose is faster than glucose. In kidney, reabsorption of filtered glucose takes place by a similar mechanism , i.e , it is also a co-transport with Na. The transporter is SGLT- 2. In intestine, it is SGLT- 1.

40. Used for facilitated transport. These transporters are numbered from 1 to 14 GLUT. In the intestine, GLUT 2 are present towards the serosal surface of intestinal epithelial cells and GLUT 5 are present towards the luminal surface .

41. Diagram showing absorption of monosaccharides

42. Purpose of GLUT 5 and GLUT 2

43. The absorption is faster through intact mucosa. The absorption is decreased if there is some inflammation or injury to the mucosa. Thyroid hormones ↑ the rate of absorption of glucose. Mineralocorticoid,i.e A ldosterone ↑ the rate of absorption.

44. Vitamin B6,B12, pantothenic acid, folic acid are required for absorption of glucose. With advancing age, rate of absorption declines. Note: Insulin has no role in the absorption of monosaccharide like glucose .

45. Mechanism: facilitated diffusion. There are 7 important glucose transporter for uptake of glucose into special cells. They have been numbered from 1 to 7 (GLUT 1 to GLUT 7). They are biologically important.

46. Tissue specific glucose transporter Tissue distribution Functions Clinical significance GLUT-1 (great affinity for glucose) Present in almost all cells with an abundance in RBC. Na-independent Cancer cells express high level of GLUT-1, so they can internalize more of glucose, which is used as a source of energy for rapidly dividing cells. GLUT-2 (low affinity for glucose , it can transport only when there is glucose load in the body) Present in intestine, liver and pancreas. Release s insulin by movement of glucose into β -cells of pancreas. (Acts as a sensor for the release of insulin by pancreas .) Promotes uptake of glucose in liver cells, lowering down blood glucose. Diabetes Mellitus.

47. GLUT 3 Brain cells, all other cells of body Cancer cells express high level of GLUT-3, so they can internalize more of glucose, which is used as a source of energy for rapidly dividing cells GLUT 4 Adipose tissue, skeletal muscles , cardiac muscles The only transporters which are under the influence of insulin. Insulin promotes uptake of glucose in the tissues by mobilizing the transporters to the cell surface whenever there is high glucose concentration in the blood.

48. GLUT 5 (least affinity for glucose) Intestine at the luminal surface, testicles, seminal vesicles Mainly for the transport of fructose GLUT 6 Non-functional transporter product of a pseudogene . No role in absorption of glucose in peripheral cells. GLUT 7 Surface of endoplasmic reticulum Transportation of glucose across the membrane of endoplasmic reticulum. SGLT 1 Kidney, intestine For the absorption of glucose. In cases where SGLT 1 is deficient, glucose is left unabsorbed and is excreted in faeces . SGLT 2 Kidney For the re-absorption of glucose. If deficient, filtered glucose is not re-absorbed and is lost in urine.

49. References www.namrata.co- Biochemistry for medics Lecture notes Sciencephotolibrary

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