CARBOHYDRATE METABOLISM

1. CARBOHYDRATE METABOLISM Dr. Esam Abdelraheem Alaraby Ph. D Clinical Biochemistry and Stem cells therapy.

2. Dietary carbohydrates • 1- Monosaccharides :- • Glucose : in frutes especially grape ( grape suger) • Fructose : in frutes and honey • 2- Disaccharides: • Sucrose : called table suger or cane suger • Maltose: called malt suger • Lactose: in milk

3. -Polysaccharides: • Sarch: storage form of carbohydrates in plants. It is the most common carbohydrate in human diets and is contained in large amounts in foods like potatoes, wheat, rice, • Cellulose : in wall of plants .

4. Digestion of carbohydrates- Carbohydrates form 60% of human food and are present in three forms:1- Digestible carbohydrates: Disaccharides, oligo-saccharides and Some polysaccharides.2- Absorbable carbohydrates: monosaccharides3-Non-digestible Non absorbable carbohydrates: Some polysaccharides as celluose ,hemicellulose, lignin, gums and pectins.

5. Sites of carbohydrate digestion: • Buccal cavity. • Stomach. • Small intestine.

6. Carbohydrate Digestion in the buccal cavity:salivary amylase (-glycosidase) from salivary glands. Its optimum pH is 6.7 - 6.8 and is activated by chloride ions. It is a -glycosidase specific for hydrolysis of -1,4 glucosidic linkage of cooked starch and glycogen producing maltose and dextrins (not -1,4-glucosidic linkage of maltose).

7. Salivary amylaseCooked starch  Amylodextrin (Violet with iodine) + maltose + isomaltose Salivary amylaseAmylodextrin  Erythrodextrin (Red with iodine) + maltoseSalivary amylaseErythrodextrin  Achrodextrin (Colorless with iodine) + maltose

8. Since starch and glycogen contains glucose units linked by α-1,6 glucosidic linkage at the branching points, salivary amylase also produces isomaltose. • Because food remains in the mouth for a short period, starch digestion by salivary amylase is incomplete. The products of salivary amylase digestion are Starch dextrins, maltose and isomaltose.

9. Carbohydrate digestion in the Stomach: • - Salivary amylase continues to act on starch, glycogen or dextrins for 2 - 3 minutes only in the stomach (acidic pH 1 - 2).

10. . Carbohydrate digestion in the Small Intestine:- In the small intestine, there are two juices that digest carbohydrates:A. The pancreatic juice: contains pancreatic amylase, -an -glycosidase- optimum pH 7.1 - activated by chloride ion.- digesting cooked and uncooked starch, glycogen and starch dextrins which escaped digestion by salivary amylase in the mouth producing maltose, maltotriose (three -glucose residues linked by -1,4 bonds) and a mixture of branched oligosaccharides (-limited dextrins),

11. B. Intestinal mucosal brush border enzymes: • The final digestion of carbohydrates occurs in the small intestine by the action of the following disaccharidases:

12. Lactase • Lactose  Glucose + galactose Maltase • Maltose  Glucose + glucose • -Dextrinase (oligo 1-6 glucosidase) hydrolyzes isomaltose, -Dextrinase or Isomaltase • Isomaltose  glucose + glucose

13. Sucrase (invertase) • Sucrose  Glucose + fructose. • - Thus, carbohydrates are digested into glucose, galactose, mannose and fructose.

16. lactose intolerance: • Lactase deficiency • Lactase (-galactosidase) hydrolyzes • lactose into glucose and galactose • Causes:- • inherited • age-dependent decline of enzyme expression • acquired medical problem due to intestinal diseases such as sprue, colitis, kwashiorkor and gastroenteritis.

18. Symptoms:- • abdominal cramps, • Diarrhea(osmotic diarrhea), • Flatulence(Distention) on eating fresh and non-fermented milk products. • Treatment: Lactose free milk or -galactosidase therapy.

20. Mechanism:- (pathogenesis) The presence of lactose in intestine causes : • a) Increased osmotic pressur e : So water will be drawn from the tissue (causing dehydration) into the large i ntestine (causing osmotic diarrhea). • b) Increased fermentation of lactose bacteria Intestinal bacteria ferment lactose with subsequent production of C02 gas. This causes distention (flatulance) and abdominal cramps.

22. Treatment: Treatment of this disorder is simply by : 1- Lactose free milk formula during lactation. 2- B-galactoidase(lactase) therapy in form drops or tablets before meal.

25. Sucrase deficiency: • It is a rare condition, showing a similar • signs and symptoms as lactase deficiency. • It occurs early in childhood .

26. Dietary fibers • - Not digestable: • The -1,4 glucosidic linkage of Cellulose is not hydrolyzed by human digestive enzymes. Hemicellulose, lignin, gums, pectins and pentosans are also indigestible. • Importance: • 1- prevents constipation • - Cellulose and other dietary fibers passes as it is in stools, increasing bulk of intestinal contents by adsorbing water and stimulates peristaltic movements .

27. 2- High-fiber diet is beneficial by reducing the incidence of diverticulosis, cancer of the colon, cardiovascular disease and diabetes mellitus. • 3- Reduces stool transit time and and lower contact with fecal mutagens. They bind and dilute bile acids (cocarcinogens)

28. 4- Fermentation of fibers by large intestinal bacteria gives butyric acid that stabilizes the differentiated state of colon cells against a host of mutagens in food and water. • 5- The more soluble fibers found in legumes and fruit, e.g., gums and pectins, lower blood cholesterol, possibly by binding bile acids and dietary cholesterol

29. 6- The soluble fibers also slow the stomach emptying and attenuate the post-prandial rise in blood glucose that spares insulin. This effect is beneficial to diabetics and to dieters because it reduces the rebound fall in blood glucose that stimulates appetite.

30. 7- It induces establishment of normal colon bacteria with several benefits including fermentation of fibers and production of vitamins (e.g., vitamin K and biotin). • - However, excessive dietary fibers, e.g., bran chelate calcium in an insoluble form.

31. Absorption • Site of absorption: • - Mainly the upper part of small intestine, i.e., jejunum. Very small amount is absorbed in the stomach or large intestine. • Route of absorption: • - By the portal vein to the liver, i.e., blood stream chiefly in the form of hexoses (glucose, fructose, mannose and galactose) and as pentose sugars (ribose).

32. A) Active absorption: Mechanism of Absorption • - It needs a sodium-dependent glucose co-transporters, e.g., SGLT1. It absorbs hexose against their concentration gradient. • - Mobile carrier protein in the apical (lumenal) memb. of intestine.and kidney • - Glucose transporter has at least 2 sites, one for sodium and the other for glucose, passing sodium down its concentration gradient and glucose against its concentration gradient. • - Both sodium and glucose are released within mucosal cells. • - Na+ is pumped out again by ATP-dependent Na+-K+-exchange pump. • - There are at least two types: one is of high affinity (SGLT1in intestine) and one has low affinity (SGLT2 in kidney)). • - A Na+-independent glucose transporter, Glut2, on basal membrane transports glucose and other hexoses from mucosal and other cells into blood

34. For active transport to take place, the structure of sugar should have: • I. Hexose ring. • 2. OH group at position 2 at the right side. Both of which are present in glucose and galactose. But not in fructose.

35. Inhibitors of active transport : • a) Ouabin (cardiac glycoside): Inhibits sndium-potassium pump. • b) Phlorhizin: Inhibits the binding of sodium in the carrier( 1- 2)

36. B- Facilitated absorption • It absorbs hexoses with their conc.gradient and is Na+-independent. • - Its major role is the transport of blood sugars across cell membranes • - It utilizes at least five glucose transporters, GLUT-1 through -5

39. Fates of the body sugars In the liver fructose and galactose are changed to glucose. Glucose may undergo one of many fates, as follows, • 1- Uptake by tissues • 2- Oxidation ( major- minor) • 3- Synthesis of • carbohydrates products( fructose- galactose- lactose-glucuronic acid-amino sugers) • Non carbohydrates products( TAG -Acetyl coA gives cholesterol and fatty acids)-Non essential amino acids ( serine – alanine – aspartate – glutamate) • 4- Storage in form of (glycogen- TAG) • 5- Excretion ( Renal thresholds)

40. Glycolysis, Or Embden-Myerhof Pathway

41. - Glycolysis (from the Greek glykys, meaning “sweet,”and lysis, meaning “splitting”).- It is a sequence of reactions that converts glucose into two pyruvate molecules (when O2 is available) or into lactate (when O2 is not available, i.e., no mitochondria as in RBCs or lack of O2 as in muscle exercise). • Definition: - Aim - Production of ATP and other intermediates - utilized in gluconeogenesis (in its opposite direction) - Site - cytoplasm of all tissues of the body

42. Especially important in: • RBCs are devoid of mitochondria and depend on glycolysis as the main source of energy. Mammalian erythrocyte is unique in that about 90% of its total energy requirement is provided by glycolysis. • Cornea, lens and some parts of retina which have a limited blood supply and lack mitochondria which if present would absorb and scatter light interfering with transparency. • Kidney (medulla), testicles, leukocytes and white muscle fibers, where there are relatively few mitochondria. • Contracting muscles due to occlusion of blood vessels by the muscular contraction that decreases oxygen. • Cancer cells due to dissociation of the high rate of glycolysis from Krebs', i.e., aerobic production of lactate. • Brain and gastrointestinal tract : normally derive most of their energy from glycolysis.

43. Steps biphosphate Biphospho- glycerate 2ADP 2ATP