CARBOHYDRATE METABOLISM بايو كمستري (م 2) / د . احمد الطويل ثاني اسنان موصل 23 / 11 / 2015 CARBOHYDRATE METABOLISM Dr. Ahmed Al Taweel

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 - Fructose - Galactose Fructose and Galactose glucose at the liver

Galactose Metabolism

Fructose Metabolism

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

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

Glycolisis

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

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

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

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+

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

GLYCOLYSIS IN ERYTHROCYTE

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

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

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!)

SYNTHESIS OF GLYCOGEN

SYNTHESIS OF GLYCOGEN

GLYCOGENESIS AND GLYCOGENOLYSIS PATHWAY

Glycogenesis Glycogenolysis

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.

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

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

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

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 G-S-S-G 2-G-SH 2-G-SH + H2O2 G-S-S-G + 2H2O 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