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CARBOHYDRATE METABOLISM

CARBOHYDRATE METABOLISM. Kadek Rachmawati, M.Kes.,Drh. CARBOHYDRATE DIGESTION. AMYLUM digestion by amylase enzyme. Disaccharides digestion. Glucose is the most important carbohydrate Glucose is the major metabolic fuel of mammals, except ruminants Monosaccharide from diet :

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CARBOHYDRATE METABOLISM

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  1. CARBOHYDRATE METABOLISM Kadek Rachmawati, M.Kes.,Drh

  2. CARBOHYDRATE DIGESTION • AMYLUM digestion by amylase enzyme

  3. Disaccharides digestion

  4. Glucose is the most important carbohydrate • Glucose is the major metabolic fuel of mammals, except ruminants • Monosaccharide from diet : - Glucose - Fructose - Galactose • Fructose and Galactose glucose at the liver

  5. GalactoseMetabolism

  6. Fructose Metabolism

  7. Blood glucose carbohydrate metabolism exist are : 1. Glycolisis 2. Glycogenesis 3. HMP Shunt 4. Oxidation of Pyruvate 5. Kreb’s Cycle 6. Change to lipids • Fasting blood glucose carbohydrate metabolism : 1. Glycogenolisis 2. Gluconeogenesis

  8. GLYCOLISIS • Glycolisis oxidation of glucose energy • It can function either aerobically or anaerobically pyruvate lactate • Occurs in the cytosol of all cell • AEROBICALLY GLYCOLYSIS : Pyruvate Mitochondria oxidized to Asetil CoA Kreb’s Cycle CO2 + H2O + ATP

  9. Glycolisis

  10. Most of the reaction of glycolysis are reversible, except of three reaction : 1. Glucose Glucose-6-phosphate, catalyzed by Hexokinase / Glucokinase • Hexokinase : - Inhibited allosterically by its product glucose-6-p - Has a high affinity for its substrate glucose - available at all cell, except liver and islet cell

  11. Glucokinase : - available at liver and islet cell - in the liver to remove glucose from the blood after meal 2. Fructose-6-P Fructose-1,6-biP - catalyzed by Phosphofructokinase enzyme - Irreversible - Rate limiting enzyme in glycolysis 3. Phosphoenolpyruvate Enol Pyruvate - Catalyzed by Pyruvate kinase enzyme • Oxidation of 1 mol glucose 8 mol ATP and 2 mol Pyruvate

  12. ANAEROBICALLY GLYCOLYSIS : - The reoxidation of NADH through the respiratory chain to oxygen is prevented - Pyruvate is reduced by the NADH to lactate, by Lactate dehidrogenase enzyme Lactate dehydrogenase • Pyruvate + NADH + H+ Lactate + NAD+ - Oxidation 1 mol glucose via anaerobically glycolysis 2 mol ATP

  13. ANAEROBICALLY GLYCOLYSIS : Respiratory chain is absence Reoxidation of NADH NAD+ via Respiratory chain is inhibited Reoxidation of NADH via lactate formation allows glycolysis to proceed in the absence of oxygen by regenerating sufficient NAD+

  14. GLYCOLYSIS IN ERYTHROCYTE • Erythrocyte lack mitochondria respiratory chain and Kreb’s cycle are absence • Always terminates in lactate • In mammals the reaction catalyzed by phosphoglycerate kinase may be bypassed by a process that catalyzed Biphosphoglycerate muta- se • Its does serve to provide 2,3-biphosphoglycerate bind to hemoglobin decreasing its affinity for oxygen oxygen readily available to tissues

  15. GLYCOLYSIS IN ERYTHROCYTE

  16. OXIDATION OF PYRUVATE • Occur in mitochondria • Oxidation of 1 mol Pyruvate 1 mol Asetyl-CoA + 3 mol ATP • CH3COCOOH + HSCoA + NAD+ CH3CO-SCoA + NADH (Pyruvate) (Asetyl-CoA) • Catalyzed by Pyruvate dehydrogenase enzyme • This enzyme need CoA as coenzyme • In Thiamin deficiency, oxydation of pyruvate is impaired lactic and pyruvic acid

  17. OXIDATION OF PYRUVATE

  18. GLYCOGENESIS • Synthesis of Glycogen from glucose • Occurs mainly in muscle and liver cell • The reaction : • Glucose Glucose-6-P Hexokinase / Glucokinase • Glucose-6-P Glucose-1-P Phosphoglucomutase • Glucose-1-P + UTP UDPG + Pyrophosphate UDPG Pyrophosphorylase

  19. GLYCOGENESIS • Glycogen synthase catalyzes the formation of α-1,4-glucosidic linkage in glycogen • Branching enzyme catalyzes the formation of α-1,6-glucosidic linkage in glycogen • Finally the branches grow by further additions of 1 → 4-gucosyl units and further branching (like tree!)

  20. SYNTHESIS OF GLYCOGEN

  21. SYNTHESIS OF GLYCOGEN

  22. GLYCOGENESIS AND GLYCOGENOLYSIS PATHWAY

  23. Glycogenesis Glycogenolysis

  24. GLYCOGENOLYSIS • The breakdown of glycogen • Glycogen phosphorilase catalyzes cleavage of the 1→4 linkages of glycogen to yield glucose-1-phosphate • α(1→4)→α(1→4) glucan transferase transfer a trisaccharides unit from one branch to the other • Debranching enzyme hydrolysis of the 1→6 linkages • The combined action of these enzyme leads to the complete breakdown of glycogen.

  25. GLYCOGENOLYSIS Phosphoglucomutase • Glucose-1-P Glucose-6-P Glucose-6-phosphatase • Glucose-6-P Glucose • Glucose-6-phosphatase enzyme a spesific enzyme in liver and kidney, but not in muscle • Glycogenolysis in liver yielding glucose export to blood to increase the blood glu- cose concentration • In muscle glucose-6-P glycolysis

  26. GLUCONEOGENESIS • Pathways that responsible for converting noncarbohydrate precursors to glucose or glycogen • In mammals occurs in liver and kidney • Major substrate : 1. Lactic acid from muscle, erythrocyte 2. Glycerol from TG hydrolysis 3.Glucogenic amino acid 4. Propionic acid in ruminant

  27. Gluconeogenesis meets the needs of the body for glucose when carbohydrate is not available from the diet or from glycogenolysis • A supply of glucose is necessary especially for nervous system and erythrocytes. • The enzymes : 1. Pyruvate carboxylase 2. Phosphoenolpyruvate karboxikinase 3. Fructose 1,6-biphosphatase 4. Glucose-6-phosphatase

  28. GLUCONEOGENESIS

  29. GLUCONEOGENESIS FROM AMINO ACID

  30. GLUCONEOGENESIS FROM PROPIONIC ACID

  31. CORY CYCLE

  32. HMP SHUNT/HEXOSE MONO PHOSPHATE SHUNT = PENTOSE PHOSPHATE PATHWAY • An alternative route for the metabolism of glucose • It does not generate ATP but has two major function : 1. The formation of NADPH synthesis of fatty acid and steroids 2. The synthesis of ribose nucleotide and nucleic acid formation

  33. HMP SHUNT • Active in : liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testis and lactating mammary gland • Its activity is low in muscle • In erythrocytes : • HMP Shunt provides NADPH for the reduction of oxidized glutathione by glutathione reductase reduced glutathi- one removes H2O2 glutathione peroxidase

  34. HMP SHUNT Glutathione reductase • G-S-S-G 2-G-SH (oxidized glutathione) (reduced glutathione) Glutathione peroxidase • 2-G-SH + H2O2 G-S-S-G + 2H2O • This reaction is important accumulation of H2O2 may decrease the life span of the erythrocyte damage to the membrane cell hemolysis

  35. HMP SHUNT

  36. BLOOD GLUCOSE • Blood glucose is derived from the : 1. Diet the digestible dietary carbohy- drate yield glucose blood 2. Gluconeogenesis 3. Glycogenolysis in liver • Insulin play a central role in regulating blood glucose blood glucose • Glucagon blood glucose • Growth hormone inhibit insulin activity • Epinefrine stress blood glucose

  37. Good luck!! Thank you

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