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CHO lec1.ppt
- 1. Carbohydrate metabolism CHO Digestion • Carbohydrate: polyhydroxy aldehyde or ketone • Carbohydrate classification – Monosaccharide (glucose, fructose, galactose mannose) – Di saccharides (maltose, lactose, sucrose, isomaltose) – Polysaccharides (cellulose, starch, glycogen) Introduction
- 2. DIETARY CARBOHYDRATES • Normal diet contains 200-300 g (50% of caloric intake) • Serves an energy and carbon source • Digestion includes a luminal phase and a brush border phase • Only monosaccharaides are appreciably absorbed Introduction
- 3. Starch= Amylose & Amylopectin
- 4. • alpha-Amylase (pH optima 7) cleaves interior α1-4 linkages but not α1-6 • End product is a mixture of maltose, maltotriose and limit dextrin • Acarbose (anti diabetic drug) – Amylase inhibitor Introduction
- 5. Introduction Intestinal brush border hydrolysis Products site of hydrolysis Substrates Enzyme Glucose α- 1,4 linkage Maltose , maltotriose Maltase Glucose fructose α- 1,2 linkage Sucrose Sucrase Glucose, galactose β- 1,4 linkage But not of cellulose Lactose Lactase Glucose, maltose, oligosaccharides α- 1,6 linkage α- limit dextrins α- dextrinase (Isomaltase)
- 6. Maltose
- 10. SGLT1 Na+ - glucose symporter Absorption of carbohydrate Introduction
- 11. • The glucose and galactose is taken up by a Na+-monosaccharide co-transporter,. • Na+ will be pumped out by Na+ K+–ATP-ase. • Fructose is taken up by Na+ -independent facilitated-diffusion, mediated by GLUT5. • The monosaccharides could leave enterocytes into interstitial through GLUT2. Absorption of carbohydrate Introduction
- 12. Lactase Deficiency Lactose accumulation In bowel lumen Increased luminal osmolality Watery diarrhea Lactic acid Production By bacteria Net water accumulation in lumen Luminal distention Enhanced peristalsis Introduction
- 13. Lactase is present in infancy and disappears to a variable extent during childhood in most humans. Exception is Northern Europeans and European Americans-commonly retain lactase into adulthood. Introduction
- 14. Sucrase Deficiency Sucrase accumulation In bowel lumen Increased luminal osmolality Watery diarrhea Lactic acid Production By bacteria Net water accumulation in lumen Luminal distention Enhanced peristalsis Introduction
- 15. • Blood Transport: (portal vein to liver): • 1. Release monosaccharides into bloodstream • 2. Deliver sugars for storage as glycogen (liver, muscle tissue ) or fat (adipose tissue) Blood transport Introduction
- 16. • GLUT proteins Na+ -independent monosaccharide transporters are responsible for the thermodynamically downhill movement of glucose across the plasma membrane of animal cells. – GLUT 1: red blood cells, brain, adipose tissue – GLUT 2: liver, pancreatic β cells, kidney – GLUT 3: brain – GLUT 4: muscle, adipose tissue (insulin dependent) – GLUT 5: fructose transporter Introduction
- 17. This experiment was performed in the culture of adipocytes by attaching green fluorescent protein to GLUT4 Change of the localization of GLUT4 glucose transporter protein treated with insulin Introduction
- 18. PET scans can image biological processes within the body. Glucose metabolism significance
- 19. Glucose metabolism significance Positron emission tomography (PET) :Injection with 18fluorodeoxyglucose (short-lived radioactive element: fluorine-18 and glucose) to track glucose metabolism and therefore brain activity – glucose is virtually the only energy source in the brain in normal. Introduction
- 20. Glucose metabolism significance Diabetes • related to blood glucose concentration • altered ability to regulate glucose metabolism • normally: when [glucose] high, insulin is released • T1DM lack the ability to secrete insulin •T2DM insulin resistance and decrease to secrete insulin Cancer • glucose uptake/glycolysis ~ 10x faster in cancer cells • some glycolytic enzymes are overproduced Introduction
- 21. CT scan PET
- 22. glucose Sources: 1.Endogenous 2.Exogenous • The daily requirement of glucose for the human body is about 160 g, from which 120 g is utilized by the brain. Carbohydrate metabolism
- 23. Carbohydrate metabolism Glycolysis & the Oxidation of Pyruvate 1. Glycolysis 2. Gluconeogenesis 3. Glycogenolysis 4. Glycogenesis
- 24. Summary of glycolysis. − , blocked by anaerobic conditions or by absence of mitochondria containing key respiratory enzymes, eg, as in erythrocytes
- 25. Glycolysis
- 26. Glycolysis cont.
- 28. Characteristic features of glycolysis Localized in the cytosol An ancient metabolic pathway • Could produce ATP without using molecular oxygen
- 29. Glycolysis is a preparatory pathway for aerobic metabolism of glucose TCA
- 30. The Oxidation of Pyruvate to form Acetyl CoA for Entry Into the Krebs Cycle Pyruvate dehydrogenase (complex enzyme) convert pyruvate into acetyl CoA •2 NADH's and 2 CO2 are generated (1 per pyruvate)
- 31. .Three possible catabolic fates of the pyruvate formed in glycolysis. Pyruvate also serves as a precursor in many anabolic reactions, not shown here
- 32. Generation of high-energy phosphate in the catabolism of glucose.
- 33. CLINICAL ASPECTS • Inhibition of Pyruvate Metabolism Leads to Lactic Acidosis • 1- Arsenite and mercuric ions inhibit pyruvate dehydrogenase • 2- Dietary deficiency of thiamin (cofactor of pyruvate dehydrogenase,), allowing pyruvate to accumulate.
- 34. • 3- Inherited pyruvate dehydrogenase deficiency - causes lactic acidosis, particularly after a glucose load. – neurologic disturbances because Brain is dependences on glucose as a fuel CLINICAL ASPECTS
- 35. • Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. CLINICAL ASPECTS Pphosphofructokinase deficiency The exercise capacity of muscle is low, particularly on high carbohydrate diets. The capacity is improved By providing lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased.