Carbohydrate Metabolism.pdf

METABOLISM Metabolism ❖ Bioenergetics is the transfer and utilization of energy in biological systems ❖ Metabolism is the assembly of biochemical reactions used by an organism for the synthesis of cell materials and the utilization of energy from the environment ❖ Metabolism → Anabolic (assimil...

METABOLISM Metabolism ❖ Bioenergetics is the transfer and utilization of energy in biological systems ❖ Metabolism is the assembly of biochemical reactions used by an organism for the synthesis of cell materials and the utilization of energy from the environment ❖ Metabolism → Anabolic (assimilation) or Catabolic (dissimilation) http://web.virginia.edu/Heidi/chapter18/Images/8883n18_04.jpg Metabolism ❖ Anabolic reactions are the synthesis of large molecules from simple or smaller molecules ❖ Energy is used in the process → Endergonic A + B → AB [+∆G] ∆G = ∆product - ∆reactants where ∆G is the free energy change of a reaction ❖ Example, Photosynthesis sunlight; chlorophyll carbon dioxide + water → carbohydrate + oxygen Metabolism ❖ Catabolic reactions are the breakdown of large molecules to smaller or simpler molecules ❖ Energy is released in this process → Exergonic e.g. digestion AB → A + B [- ∆G] ❖ Three stages of catabolism – ∆G = ∆product - ∆reactants Metabolic Map Carbohydrate Metabolism Carbohydrate Metabolism ❖ Carbohydrates are metabolized to yield a vast array of other organic compounds ❖ Animals ingest large quantities of carb. that can either be stored, oxidized to obtain energy, converted to lipid for more efficient energy storage or use for the synthesis of many cellular constituents ❖ Major function is to be oxidized and provide energy for metabolic processes ❖ Carbohydrate is utilized by the cells mainly as glucose ❖ Fructose and galactose are easily converted to glucose in the liver Carbohydrate Metabolism Catabolic Reactions Anabolic Reactions Glycolysis Gluconeogenesis Glycogenolysis ❖ Other reactions include TCA Cycle, Oxidative phosphorylation and electron transport Glycolysis ❖ This is a process by which glucose is broken down to produce energy to all cells Glucose (6 C) 2 Pyruvate + 2 ATP + 2H+ (3 C) ❖ It occurs in the cytoplasm of the cell ❖ It is a hub of carbohydrate metabolism because all sugars (whether from diet or via catabolic reactions) can be converted to glucose Glycolysis  http://www.bioinfo.org.cn/book/biochemistry/chapt14/si m1.htm - Glycolysis Total Input Total Output 1 molecule of glucose (6 C) 2 molecules pyruvate (3 C) 2 ATP 4 ATP 4 ADP 2 ADP 2 NAD+ 2 NADH 2 Pi 2 H2O Net gain = 2 ATP Glycolysis ❖ The fate of pyruvate depends on the availability of oxygen ❖ If oxygen is present, pyruvate enters the mitochondria and will be oxidised to carbon dioxide and water (aerobic respiration) ❖ If oxygen is absent then pyruvate is converted into alcohol or lactate (anaerobic respiration) http://www.bioinfo.org.cn/book/biochemistry/chapt14/403.jpg Aerobic Respiration ❖ This involves two phases 1. Oxidative decarboxylation of pyruvate – removal of CO2 and oxidation (removal of hydrogen) 2. Carboxylation of acetyl CoA to oxaloacetate Oxidative Decarboxylation of Pyruvate ❖ Occurs in the mitochondria (matrix) Oxidative Decarboxylation of Pyruvate ❖ Pyruvate + coenzyme A (CoASH) + NAD+ pyruvate dehydrogenase acetyl CoA + CO2 + NADH + H+ ❖ Acetyl CoA ❖ NADH + H+ → → TCA cycle respiratory chain in the mitochondria ❖ A deficiency in pyruvate dehydrogenase leads to lactic acidosis, due to the prevention of acetyl CoA formation from pyruvate. The pyruvate therefore forms lactic acid. ❖ TCA cycle provides most of the energy needed for the brain Oxidative Decarboxylation of Pyruvate ❖ Since the TCA process is hindered when there is a deficiency in pyruvate dehydrogenase … ❖ Developmental defects of the brain and nervous system can occur Carboxylation of Pyruvate http://www.bioinfo.org.cn/book/biochemistry/chapt15/453.jpg Carboxylation of Pyruvate ❖ Since the oxidation of 1 molecule glucose ↓ 2 molecules of acetyl CoA ❖ The TCA cycle occurs twice for every molecule of glucose oxidized ❖ The net result is 2 ATP and 4 CO2 ❖ The overall reaction for glycolysis, acetyl CoA formation and TCA cycle is C6H12O6 + 6 H2O 6CO2 + 4 ATP + 12 H+ Energy from Acetyl CoA Anaerobic Respiration In animals This occurs in the red blood cells, exercising muscles and anoxic tissues Anaerobic Respiration In Plants Pyruvate + NADH + H+ Ethanol + CO2 + NAD+ ❖ This occurs in yeast cells and other microorganisms Electron Transport Chain ❖ The reaction occurs in the inner mitochondrial membrane ❖ Electrons from intermediates in Glycolysis and the TCA cycle are donated to specific coenzymes (NAD+ and FAD) to form energy rich reduced co-enzymes (NADH and FADH2) ❖ Each reduced co-enzyme donate a pair of electrons to electron carriers (NADH dehydrogenase (Complex 1), flavoprotein (Complex II), coenzyme Q (ubiquinone), cytochrome bc1 (Complex III) , cytochrome c (Complex IV) and cytochrome a+a3 (Complex V) ❖ As electrons are passed down the chain they lose some of their free energy ❖ At the end of the chain, hydrogen combines with oxygen to form water Oxidative Phosphorylation ❖ Oxidative phosphorylation is the process by which ATP is formed as a result of the transfer of electrons from NADH and FADH2 ❖ The reaction occurs in the inner mitochondrial membrane http://files.cellularenergytextbook.webnode.com/200000006-39b4c3aaf1/pic9.jpg Glycogenolysis ❖ This is the breakdown of glycogen in the liver and skeletal muscle to produce glucose http://chemistry.gravitywaves.com/CHE452/images/Glycogenolysis.GIF Gluconeogenesis ❖ This is the synthesis of glucose from non carbohydrate precursors ❖ The major non carbohydrate precursors are (1) Lactate – formed from pyruvate under anaerobic conditions (2) Amino acid – digestion of proteins and breakdown of proteins from skeletal muscles during starvation (3) Glycerol – hydrolysis of triglycerides ❖ This process provides a continuous supply of glucose as metabolic fuel ❖ Areas that need this continuous supply includes the brain, red blood cells, kidney medulla, lens and cornea of the eye, testes and exercising muscles Gluconeogenesis ❖ (Glycogenolysis) Stored glycogen can only provide 10 – 18 h of glucose in the absence of carbohydrate intake from the diet ❖ During an overnight fast 90% of gluconeogenesis occurs in liver 10% of gluconeogenesis occurs in kidneys ❖ In longer period of starvation glucose must be formed from non carbohydrate sources ❖ Gluconeogenesis requires both mitochondrial and cytosolic enzymes Pyruvate carboxylase is a mitochondrial enzyme Hormonal Regulation of Glucose Concentration ❖ Insulin and glucagon are the two main hormones which regulate blood glucose concentration in vivo ❖ Both are secreted by cells found in islet of Langerhans in the pancreas ❖ Insulin is secreted by the β cells when blood glucose concentration is high. Amino acids and hormones (e.g. glucagon, growth hormone, epinephrine) can also stimulate insulin secretion. ❖ Insulin decreases blood glucose by promoting glucose uptake through GLUT-4 and its use in metabolism (e.g. energy production, protein production) by liver, muscle and other tissue cells. Hormonal Regulation of Glucose Concentration ❖ When plasma insulin concentration is increased , there is an increase in the concentration of glucokinase, phosphofructokinase and pyruvate kinase in the liver thus speeding up glycolysis i.e. the conversion of glucose to pyruvate. ❖ Insulin also inhibits glucose production by inhibiting gluconeogenesis and glycogenolysis. ❖ Insulin increases fatty acid and triglyceride synthesis, thus increasing fat stores (adipogenesis), and enhances glycogen synthesis and storage in the liver. Hormonal Regulation of Glucose Concentration ❖ Glucagon is secreted by the α cells when blood glucose concentration is low. ❖ An increase in glucagon concentration decreases the concentration of glucokinase, phosphofructokinase and pyruvate kinase in glycolysis. This occurs during fasting and is also observed in diabetic individuals ❖ Glucagon also causes an increase in blood glucose, by stimulating gluconeogenesis and glycogenolysis and facilitating glucose release from hepatocytes Hormonal Regulation of Glucose Concentration ❖ Epinephrine secreted by the adrenal medulla acts via beta-adrenergic receptors increases blood glucose concentration via the stimulation of glycogenolysis and release of glucose from hepatocytes ❖ Growth hormone (GH) secreted by the pituitary glands usually in response to low blood glucose and epinephrine, increases blood glucose concentration by inhibiting glucose uptake by cells. ❖ It also promotes glycogenolysis in muscle tissue ❖ Progesterone may cause insulin resistance by stimulating secretion of GH Hormonal Regulation of Glucose Concentration  Corticosteroids secreted by the adrenal cortex, increase blood glucose by inducing glucose release from hepatocytes and inhibiting glucose uptake by cells (through decreasing GLUT-4)  Corticosteroids also stimulate gluconeogenesis and glucagon secretion (which also increases blood glucose)