CHO Metabolism Lecture 1 PDF

CHO Metabolism Professor Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  Introduction to metabolism Metabolism means the fate of food molecules after digestion and absorption. Definition: - It is the chemical enzymatic reactions occurring inside the...

CHO Metabolism Professor Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  Introduction to metabolism Metabolism means the fate of food molecules after digestion and absorption. Definition: - It is the chemical enzymatic reactions occurring inside the body and concerned with synthesis and breakdown of various substances.  Metabolic pathways of metabolism includes 1. Anabolic pathways:- – It means synthesis of complex molecules from simpler ones. – It is endergonic i.e requires free energy. – Example, synthesis of proteins. 2. Catabolic pathways:- – It means breakdown of complex molecules into simpler ones. – It is exergonic i.e releases free energy. – Example, oxidative processes that releases free energy. 3. Amphibolic pathways:- – These pathways act as link between anabolic pathways and catabolic pathways. – Example, citric acid cycle.  Food molecules Digestion Simpler molecules Absorption Amphibolic pathways Anabolic pathways Catabolic pathways 2H ~P Proteins, carbohydrates CO2 + Water Lipids, Nucleic acids….etc  Carbohydrate Metabolism CHO provides 50% of daily calories in our body. Complete oxidation of 1gm CHO gives 4 kcal. Sources of CHO in food:- 1. Starch, constitutes about 50% of dietary CHO e.g from potatoes. 2. Sucrose and lactose, constitutes most of the rest of CHO. 3. Fructose and glucose, from fruits and honey.  Digestion of CHO Polysaccharides and disaccharides must be converted to monosaccharides to be absorbed. The following enzymes are involved: 1. Salivary amylase; converts starch and glycogen into dextrins 2. Pancreatic amylase; converts dextrins into maltose. 3. Intestinal disaccharidases: Maltase converts maltose into 2 molecules of glucose Sucrase converts sucrose into glucose and fructose Lactase converts lactose into glucose and galactose  Note Lactose intolerance Definition: It is a disease which may be congenital or acquired. Cause: Deficiency of lactase enzyme. Effects: – Absence of intestinal lactase → lactose is not digested and accumulated in the intestine leading to; Intestinal bacteria Lactose Acids + Gases Fermentation Symptoms: - Abdominal distension, abdominal cramps (due to release of gases) and diarrhea (due to ↑ intestinal osmotic pressure). Treatment: Lactose free milk formula.  Metabolic pathways of carbohydrates These include the following: 1. Catabolic pathways: - involving oxidative pathways and include: Glycolysis , Hexose monophosphate shunt Uronic, acid pathway and Glycogenolysis. 2. Anabolic pathways: - these include Gluconeogenesis and Glycogenesis. 3. Amphibolic pathways: - Only citric acid cycle.  Glycolysis Definition: - It means oxidation of glucose to give pyruvate in the presence of oxygen or lactate in absence of oxygen. – It is one of the major pathways of glucose oxidation. Site:- It occurs in the cytoplasm of all tissue cells, but it is of specific importance in the following tissues; – Tissues with no mitochondria e.g RBCs, cornea and lens. – Tissues with frequent oxygen lack e.g skeletal muscles especially during exercise.  Steps It occurs in 2 stages Stage 1:- Is the energy requiring step where – One molecule of glucose is converted into 2 molecules of glyceraldhyde-3-P. It needs energy. Stage 2:- Is the energy producing stage where – Two molecules of glyceraldhyde-3-P are converted into pyruvate or lactate. It produces energy.  Importance of glycolysis 1. Energy production – Anaerobic glycolysis gives 2 ATP. – Aerobic glycolysis gives 6-8 ATP. 2. Provides the main pathway for metabolism of fructose and galactose derived from diet. 3. Good oxygenation of tissues by formation of 2,3 biphosphoglycerate which decreases the affinity of Hb to oxygen. 4. Provides important intermediates e,g – Dihydroxy acetone phosphate gives glycerol-3-P that is used for lipogenesis. – Provides pyruvate for synthesis of alanine amino acid  Energy production of glycolysis 1. ATP consumed in both aerobic and an aerobic glycolysis – 1 ATP for conversion of glucose to G-6-P. – 1 ATP for conversion of fructose-6-P to fructose 1,6 biphosphate Net energy consumed = 2 ATP. 2. ATP produced:- In case of aerobic glycolysis A. 4 ATP by substrate level phosphorylation; 2ATP for conversion of 1,3 biphosphoglycerate to 3-phosphoglycerate. 2ATP for conversion of phosphenol pyruvate into enolpyruvate. B. 4 or 6 ATP by oxidative phosphorylation in mitochondria from oxidation of 2 NADH+H+ by respiratory chain.  – Net energy gain in case of aerobic glycolysis = 4 (substrate level) + 4 or 6 (respiratory chain) = 8 - 10 ATP. – Net energy = ATP gained - ATP consumed = (8 - 10) - 2 = 6-8 ATP. In case of anaerobic glycolysis – The 2 NADH+H+ are consumed in conversion of pyruvate to lactate so the energy gained is only obtained from substrate level phosphorylation Net energy = 4 ATP - 2 ATP = 2 ATP. Substrate level phosphorylation:- – Definition: - It means phosphorylation of ADP to ATP at the level of the reaction itself without the need for the respiratory chain. e.g 1,3 biphosphoglycerate + ADP → 3 phosphoglycerate + ATP.  Glycolysis in the RBCs A. Mature RBCs contains no mitochondria, so – They depend completely upon glycolysis for energy production. – Lactate is always the end product. – The net energy = 2 ATP B. Glucose uptake by the RBCs doesn’t depend on insulin hormone. C. Production of 2,3 biphosphoglycerate.  Regulation of glycolysis The key enzymes of glycolysis are the 3 irreversible enzymes which include: - 1. Hexokinase or glucokinase. 2. Phosphofructokinase-l (PFK-1). 3. Pyruvate kinase. 1. Hormonal regulation: - Insulin stimulates the synthesis of all 3 key enzymes while glucagon inhibits their synthesis. 2. Allosteric regulation:- – G-6-F allosterically inhibits hexokinase and not glucokinase. – Fructose 2,6 biphosphate stimulates PFK-1. – Citrate inhibits PFK-1. – Fructose 1,6 biphosphate stimulates pyruvate kinase. 3. Covalent modification: - Pyruvate kinase is inactivated by phosphorylation. 4. Energy regulation: - – ATP inhibits PFK-1 and pyruvate kinase. – ADP and AMP stimulate PFK-1. Note: - Fructose 2,6 biphosphate:- It is formed from fructose-6-P by the effect of phosphofructokinase-2 as follow. PFK-2 Fructose-6-P Fructose2,6 biphosphate Fructose 2,6 biphosphate:- – Stimulates glycolysis by stimulation of phosphofructokinase-1. – It also inhibits gluconeogenesis by inhibiting fructose 1,6 biphosphatase.  In vitro inhibition of glycolysis:- 1. Arsenate competes with inorganic phosphate in the reaction Glyceraldhyde-3-P 1,3 biphosphoglycerate 2. Iodoacetate inhibits glyceraldhyde-3-P Dehydrogenase. 3. Fluoride inhibits enolase and used in clinical laboratories to inhibit glycolysis before measurement of blood glucose. Important: - Hemolytic anemia caused by deficiency of glycolysis in RBCs is most commonly due to deficiency of pyruvate kinase enzyme.