CARBOHYDRATE CARBOHYDRATE METABOLISMMETABOLISM

Kadek Rachmawati, M.Kes.,DrhKadek Rachmawati, M.Kes.,Drh

CARBOHYDRATE DIGESTION

AMYLUM digestion by amylase enzyme

Disaccharides digestion

► Glucose is the most important carbohydrateGlucose is the most important carbohydrate► Glucose is the major metabolic fuel of Glucose is the major metabolic fuel of

mammals, except ruminants mammals, except ruminants ► Monosaccharide from diet :Monosaccharide from diet :

- Glucose- Glucose

- Fructose- Fructose

- Galactose- Galactose► Fructose and Galactose glucose at the Fructose and Galactose glucose at the

liverliver

Galactose Metabolism

Fructose Metabolism

Blood glucose carbohydrate metabolism Blood glucose carbohydrate metabolism exist are :exist are :

1. Glycolisis1. Glycolisis

2. Glycogenesis2. Glycogenesis

3. HMP Shunt3. HMP Shunt

4. Oxidation of Pyruvate4. Oxidation of Pyruvate

5. Kreb’s Cycle5. Kreb’s Cycle

6. Change to lipids 6. Change to lipids Fasting blood glucose carbohydrate Fasting blood glucose carbohydrate

metabolism :metabolism :

1. Glycogenolisis1. Glycogenolisis

2. Gluconeogenesis 2. Gluconeogenesis

GLYCOLISISGLYCOLISIS

Glycolisis oxidation of glucose energyGlycolisis oxidation of glucose energy It can function either aerobically or anaerobicallyIt can function either aerobically or anaerobically

pyruvate lactatepyruvate lactate Occurs in the cytosol of all cellOccurs in the cytosol of all cell AEROBICALLY GLYCOLYSISAEROBICALLY GLYCOLYSIS : :

Pyruvate Mitochondria oxidized to Pyruvate Mitochondria oxidized to Asetil CoA Kreb’s Cycle Asetil CoA Kreb’s Cycle

CO2 + H2O + ATPCO2 + H2O + ATP

GlycolisisGlycolisis

Most of the reaction of glycolysis are reversible, Most of the reaction of glycolysis are reversible, except of three reaction :except of three reaction :

1. Glucose Glucose-6-phosphate, 1. Glucose Glucose-6-phosphate, catalyzed by Hexokinase / Glucokinasecatalyzed by Hexokinase / Glucokinase

Hexokinase :Hexokinase :

- Inhibited allosterically by its product - Inhibited allosterically by its product glucose-6-pglucose-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 :Glucokinase :

- available at liver and islet cell- available at liver and islet cell

- in the liver to remove glucose from the - in the liver to remove glucose from the blood after mealblood after meal

2. Fructose-6-P Fructose-1,6-biP2. 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 Pyruvate3. Phosphoenolpyruvate Enol Pyruvate

- Catalyzed by Pyruvate kinase enzyme- Catalyzed by Pyruvate kinase enzyme Oxidation of 1 mol glucose 8 mol ATP and 2 Oxidation of 1 mol glucose 8 mol ATP and 2

mol Pyruvatemol Pyruvate

ANAEROBICALLY GLYCOLYSIS :ANAEROBICALLY GLYCOLYSIS :

- The reoxidation of NADH through the - The reoxidation of NADH through the respiratory chain to oxygen is preventedrespiratory chain to oxygen is prevented

- Pyruvate is reduced by the NADH to lactate, by - Pyruvate is reduced by the NADH to lactate, by Lactate dehidrogenase enzymeLactate dehidrogenase enzyme

Lactate dehydrogenaseLactate dehydrogenase

Pyruvate + NADH + HPyruvate + NADH + H++ Lactate + NAD Lactate + NAD++

- Oxidation 1 mol glucose via anaerobically - Oxidation 1 mol glucose via anaerobically glycolysis 2 mol ATPglycolysis 2 mol ATP

ANAEROBICALLY GLYCOLYSIS :ANAEROBICALLY GLYCOLYSIS :

Respiratory chain is absenceRespiratory chain is absence

Reoxidation of NADH NADReoxidation of NADH NAD++ via Respiratory via Respiratory chain is inhibitedchain is inhibited

Reoxidation of NADH via lactate formation Reoxidation of NADH via lactate formation allows glycolysis to proceed in the absence of allows glycolysis to proceed in the absence of oxygen by regenerating sufficient NADoxygen by regenerating sufficient NAD++

GLYCOLYSIS IN ERYTHROCYTEGLYCOLYSIS IN ERYTHROCYTE

• Erythrocyte lack mitochondria respiratory Erythrocyte lack mitochondria respiratory chain and Kreb’s cycle are absencechain and Kreb’s cycle are absence

• Always terminates in lactateAlways terminates in lactate

• In mammals the reaction catalyzed by In mammals the reaction catalyzed by phosphoglycerate kinase may be bypassed by phosphoglycerate kinase may be bypassed by a process that catalyzed Biphosphoglycerate a process that catalyzed Biphosphoglycerate muta-muta-

sese

• Its does serve to provide 2,3-Its does serve to provide 2,3-biphosphoglyceratebiphosphoglycerate

bind to hemoglobin decreasing its affinity bind to hemoglobin decreasing its affinity for oxygen oxygen readily available to for oxygen oxygen readily available to tissuestissues

GLYCOLYSIS IN ERYTHROCYTEGLYCOLYSIS IN ERYTHROCYTE

OXIDATION OF PYRUVATEOXIDATION OF PYRUVATE

• Occur in mitochondriaOccur in mitochondria

• Oxidation of 1 mol Pyruvate 1 mol Oxidation of 1 mol Pyruvate 1 mol Asetyl-CoA + 3 mol ATPAsetyl-CoA + 3 mol ATP

• CHCH33COCOOH + HSCoA + NADCOCOOH + HSCoA + NAD++ CH CH33CO-SCoA + CO-SCoA + NADHNADH

(Pyruvate)(Pyruvate) (Asetyl-CoA) (Asetyl-CoA)

• Catalyzed by Pyruvate dehydrogenase Catalyzed by Pyruvate dehydrogenase enzymeenzyme

• This enzyme need CoA as coenzymeThis enzyme need CoA as coenzyme

• In Thiamin deficiency, oxydation of pyruvate In Thiamin deficiency, oxydation of pyruvate is impaired lactic and pyruvic acidis impaired lactic and pyruvic acid

OXIDATION OF OXIDATION OF PYRUVATEPYRUVATE

GLYCOGENESISGLYCOGENESIS

• Synthesis of Glycogen from glucoseSynthesis of Glycogen from glucose

• Occurs mainly in muscle and liver cellOccurs mainly in muscle and liver cell

• The reaction :The reaction :

• Glucose Glucose-6-PGlucose Glucose-6-P Hexokinase / GlucokinaseHexokinase / Glucokinase

• Glucose-6-P Glucose-1-PGlucose-6-P Glucose-1-P PhosphoglucomutasePhosphoglucomutase

• Glucose-1-P + UTP UDPG + Glucose-1-P + UTP UDPG + PyrophosphatePyrophosphate

UDPG PyrophosphorylaseUDPG Pyrophosphorylase

GLYCOGENESISGLYCOGENESIS

• Glycogen synthase catalyzes the formation Glycogen synthase catalyzes the formation of of αα-1,4-glucosidic linkage in glycogen -1,4-glucosidic linkage in glycogen

• Branching enzyme catalyzes the formation Branching enzyme catalyzes the formation of of αα-1,6-glucosidic linkage in glycogen-1,6-glucosidic linkage in glycogen

• Finally the branches grow by further Finally the branches grow by further additions of 1 additions of 1 →→ 4-gucosyl units and 4-gucosyl units and further branching (like tree!)further branching (like tree!)

SYNTHESIS OF GLYCOGENSYNTHESIS OF GLYCOGEN

SYNTHESIS OF GLYCOGEN SYNTHESIS OF GLYCOGEN

GLYCOGENESIS AND GLYCOGENOLYSIS GLYCOGENESIS AND GLYCOGENOLYSIS PATHWAYPATHWAY

GlycogenesisGlycogenesis Glycogenolysis Glycogenolysis

GLYCOGENOLYSIGLYCOGENOLYSISS

• The breakdown of glycogenThe breakdown of glycogen

• Glycogen phosphorilase catalyzes Glycogen phosphorilase catalyzes cleavage of the 1cleavage of the 1→4 linkages of glycogen to →4 linkages of glycogen to yield glucose-1-phosphateyield glucose-1-phosphate

• αα(1→4)→(1→4)→αα(1→4) glucan transferase transfer a (1→4) glucan transferase transfer a trisaccharides unit from one branch to the othertrisaccharides unit from one branch to the other

• Debranching enzyme hydrolysis of the 1→6 Debranching enzyme hydrolysis of the 1→6 linkageslinkages

• The combined action of these enzyme leads to The combined action of these enzyme leads to the complete breakdown of glycogen.the complete breakdown of glycogen.

GLYCOGENOLYSISGLYCOGENOLYSIS

PhosphoglucomutasePhosphoglucomutase

• Glucose-1-P Glucose-6-PGlucose-1-P Glucose-6-P

Glucose-6-phosphataseGlucose-6-phosphatase

• Glucose-6-P GlucoseGlucose-6-P Glucose

• Glucose-6-phosphatase enzyme a Glucose-6-phosphatase enzyme a spesific enzyme in liver and kidney, but not spesific enzyme in liver and kidney, but not in muscle in muscle

• Glycogenolysis in liver yielding glucose Glycogenolysis in liver yielding glucose export to blood to increase the blood glu-export to blood to increase the blood glu-

cose concentrationcose concentration

• In muscle glucose-6-P glycolysisIn muscle glucose-6-P glycolysis

GLUCONEOGENESIGLUCONEOGENESISS

Pathways that responsible for converting Pathways that responsible for converting noncarbohydrate precursors to glucose or noncarbohydrate precursors to glucose or glycogenglycogen

In mammals occurs in liver and kidneyIn mammals occurs in liver and kidney Major substrate :Major substrate :

1. Lactic acid from muscle, 1. Lactic acid from muscle, erythrocyteerythrocyte

2. Glycerol from TG hydrolysis2. Glycerol from TG hydrolysis

3.Glucogenic amino acid3.Glucogenic amino acid

4. Propionic acid in ruminant4. Propionic acid in ruminant

Gluconeogenesis meets the needs of the Gluconeogenesis meets the needs of the body for glucose when carbohydrate is not body for glucose when carbohydrate is not available from the diet or from available from the diet or from glycogenolysisglycogenolysis

A supply of glucose is necessary A supply of glucose is necessary especially for nervous system and especially for nervous system and erythrocytes.erythrocytes.

The enzymes :The enzymes :

1. Pyruvate carboxylase1. Pyruvate carboxylase

2. Phosphoenolpyruvate karboxikinase2. Phosphoenolpyruvate karboxikinase

3. Fructose 1,6-biphosphatase3. Fructose 1,6-biphosphatase

4. Glucose-6-phosphatase4. Glucose-6-phosphatase

GLUCONEOGENESISGLUCONEOGENESIS

GLUCONEOGENESIS FROM GLUCONEOGENESIS FROM AMINO ACIDAMINO ACID

GLUCONEOGENESIS FROM GLUCONEOGENESIS FROM PROPIONIC ACIDPROPIONIC ACID

CORY CYCLECORY CYCLE

HMP SHUNT/HEXOSE MONO HMP SHUNT/HEXOSE MONO PHOSPHATE SHUNT = PENTOSE PHOSPHATE SHUNT = PENTOSE

PHOSPHATE PATHWAYPHOSPHATE 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 SHUNTHMP 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 SHUNTHMP 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 SHUNTHMP SHUNT

BLOOD GLUCOSEBLOOD 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

Good luck!! Thank youGood luck!! Thank you