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 : - Glucose - Glucose - Fructose - Fructose - Galactose - Galactose ► Fructose and Galactose glucose at the liver

Galactose Metabolism

Fructose Metabolism

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

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

Glycolisis

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

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

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

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

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

GLYCOLYSIS IN ERYTHROCYTE

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

OXIDATION OF PYRUVATE

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

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

SYNTHESIS OF GLYCOGEN

GLYCOGENESIS AND GLYCOGENOLYSIS PATHWAY

Glycogenesis Glycogenolysis

GLYCOGENOLYSIS The breakdown of glycogen The breakdown of glycogen Glycogen phosphorilase catalyzes cleavage of the 1 →4 linkages of glycogen to yield glucose-1- phosphate 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 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 Debranching enzyme hydrolysis of the 1→6 linkages The combined action of these enzyme leads to the complete breakdown of glycogen. The combined action of these enzyme leads to the complete breakdown of glycogen.

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

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

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

GLUCONEOGENESIS

GLUCONEOGENESIS FROM AMINO ACID

GLUCONEOGENESIS FROM PROPIONIC ACID

CORY CYCLE

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

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

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

HMP SHUNT

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

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