FLGX 224 CAROHYDRATE METABOLISM.pptx

Carbohydrate metabolism Marsoné Stander 084 206 6656 Outcomes Discuss the role of carb metabolism Discuss the formation and storage of glycogen in the body Compare the metabolic pathways such as glycolysis, Krebs cycle, oxidative phosphorylation, pentose pathway Discuss the control of glycoly...

Carbohydrate metabolism Marsoné Stander 084 206 6656 Outcomes Discuss the role of carb metabolism Discuss the formation and storage of glycogen in the body Compare the metabolic pathways such as glycolysis, Krebs cycle, oxidative phosphorylation, pentose pathway Discuss the control of glycolysis by ATP-and ADP- concentrations Describe gluconeogensesis and the regulation thereof Presentation title 2 Recommended: Please go through these slides with your Guyton and Hall textbook. These slides are based on chapter 69 p843-852 Presentation title 3  Outcome 1: the central role of glucose in carbohydrate metabolism Presentation title 4 The release of energy from foods Chemical reactions in cells are for making energy in foods available to the physiological systems of the cell. Energy is needed for muscle act, secretion by glands, maintenance of mebrane potentials by nerve and muscle fibers, synthesis of substances by cells, absorption by the digestive system. Carbs, fats, proteins are oxidized and large amounts of energy is released. The release of energy from foods -To provide energy for muscle act ( just an example) the chemical reactions need to be coupled with the system responsible for these physiological functions. -Coupling is achieved by cellular enzymes and energy transfer systems. -Free energy: the amount of energy liberated by the complete oxidation of food (ΔG) -1 mole glucose (180g) = 686,00 calories -ATP: energy currency of the body -Energy derived from oxidation of foods are used to convert ADP into ATP ( this always maintains ATP supply -ATP= Adenine + 3 (Tri) Phosphate radicals -The last two phosphate radicals are connected with high energy bonds - loss of first phosphate= ADP -Presentation Loss of title second phosphate= AMP 6  The final products of carb digestion= glucose, fructose, galactose. Fructose and galactose are converted to glucose in the liver Glucose becomes the final common The role of pathway for transport of almost all carbohydrates to the tissue cells. glucose in When liver releases monosaccharides back into the blood, almost all = glucose carb Liver cells contain glucose phosphatase (glucose-6-phosphatase) can be metabolis degraded to glucose+ phosphate, glucose can be transported through the m liver cell membrane back to into the blood. Before cells can use glucose it must be transported into the cytoplasm by facilitated diffusion. Presentation title 7  @ the cell membrane there are large amounts of protein carrier molecules Glucose binds to these protein carrier molecules and are transported to from the membrane to the cytoplasm The role of Glucose will transport from a high concentration area to a low glucose in concentration area Diffusion of glucose through Gi carb membrane/ epithelium of renal tubes: metabolis Glucose is transported by a mechanism of sodium-glucose co-transport, in which active transport of sodium provides m energy for absorption of glucose against the concentration difference Insulin concentration increases during facilitated diffusion of glucose Presentation title 8 Interconve ersions of the the major monosacch arides in liver cells Presentation title 9  Outcome 2 Discuss the formation and storage of glycogen in the body  -When glucose enters the cell cytoplasm, it immediately combines with a phosphate radical. The -Phosphorylation by glucokinase happens in the liver, and phosphorylation by hexokinase happens in the phosphoryl other cells -The process of phosphorylation is irreversible. ation of -Except in the liver cells, renal tubular epithelial cells, intestinal epithelial cells. The reversibility of this glucose process is caused by the glucose phosphatase enzyme in these cells. - Phosphorylation function: capture the glucose in the cell so that glucose cannot diffuse out. - Glucose can be used immediately for release of energy into the cell, or stored as glycogen in liver and muscle cells. - Glycogen molecules can be polymerized to any molecular weight, and precipitates into solid granules. Glycogenesis Glycogenesis: formation of glucose Glucose-6-phosphate becomes glucose-1-phosphate and is then converted to uridine diphosphate glucose and is then finally converted to glucose Lactic acid, glycerol, pyruvic acid and deaminated amino acids can also be converted to glucose Presentation title 12 Glycogenolysis - Glycogenolysis: breakdown of the cell’s stored glycogen to re-form glucose in the cells - Glucose can then be used to provide energy - Each glucose molecule on each branch of glycogen polymer is split away by phosphorylation (catalyzed by phosphorylase) - This catalyst must first be activated before phosphorylation can take place by glucagon and epinephrine - Epinephrine: hormone secreted by the adrenal medullae when sympathetic nervous system is stimulated - 1 function of the sns is to increase the availability of glucose for rapid energy metabolism. This occurs in the liver cells and muscles, which contribute to the preparation of the body for action - Glucagon: hormone secreted by the alpha cells of the pancreas when blood glucose concentration falls too low. Glucagon stimulates the formation of cyclic-AMP in the liver cells. Glucagon promotes the conversion of liver glycogen to glucose and its release into the blood which in turn elevates the blood glucose concentration. Presentation title 13 Glycogenesis and Glycogenolysi s Presentation title 14  Outcome 3 Compare the metabolic pathways such as glycolysis, Krebs cycle, oxidative phosphorylation, pentose pathway Release of energy from glucose by the glycolytic pathway Energy would be wasted if glucose were decomposed all at once into water and carbon dioxide while From one molecule of ATP at forming only a single ATP molecule a time Fortunately cells contain special This forms 38 moles of ATP enzymes for each 1 mole of glucose Enzymes cause glucose metabolized by the cells molecules to split a little at a time in many steps Step 1 of glucose So that energy can be released in degradation is glycolysis small pockets to Presentation title 16 Step 1:Glycolysis Glycolysis: splitting glucose to form 2 molecules of pyruvic acid There are 10 chemical reactions Each step is catalysed by a specific enzyme The process begins where glucose is first converted to fructose- 1,6-diphosphate , then split into 2x ( glyceraldehyde-3- phosphate) molecules, each of these molecules are converted through 5 additional steps into pyruvic acid. 2 moles ATP are formed for each molecule glucose utilized Presentation title 17 Glycolysis Presentation title 18 Step 2: conversion of Pyruvic acid to Acetyl coenzyme A Two carbon dioxide molecules and four hydrogen atoms are released from this reaction, the remaining portions of the 2 Pyruvic acid molecules combine with co-enzyme A and form 2 molecules of Acetyl-CoA No ATP is formed during this conversion Presentation title 19 Step 4: Citric acid / Krebs cycle Krebs Cycle: a sequence of chemical reactions in which the acetyl portion of acetyl coenzyme A is degraded to carbon dioxide and hydrogen atoms. These reactions occur in the matrix of the mitochondria Hydrogen atoms are the atoms that will be oxidised, which will release a large amount of energy to form ATP @ start and end of the Krebs cycle oxaloacetic acid is present, cycle begins with oxaloacetic acid and ends with the formation of oxaloacetic acid. At the start of the cycle, acetyl co-A combines with oxaloacetic acid and form citric acid. The co-A portion of is released and can be used repeatedly to form additional quantities of acetyl co-A from pyruvic acid Pyruvic acid+ Co-A = acetyl co-A + 2CO2 + 4H Acetyl part becomes NB part of citric acid molecule Lots of water molecules are added throughout the cycle, leaving products of CO2 and H+ @ other stages of the cycle Presentation title 20 Krebs cycle For each molecule of glucose metabolised, 2 acetyl co-A molecules and 6 water molecules enter Krebs cycle These molecules are then degraded to 4 Co2 molecules,16 H+ atoms and 2 molecules of Acetyl co-A. 2molecules of ATP are formed The Krebs cycle does not cause great amount of energy to be released Only the step of alpha-ketoglutaric acid converted to succinic acid ( 1 mole of ATP is only formed during this step) For each molecule glucose metabolized, 2 mol of acetyl-coA molecules pass through the citric acid cycle, forming 2 mol ATP Presentation title 21 Krebs cycle Presentation title 22 Krebs cycle 24 H atoms are released for each original molecule of glucose ( 4 during glycolysis, 4 during formation of acetyl co-A, 16 during Krebs Cycle) Hydrogen atoms released in packets of 2, in each case the release is catalysed by dehydrogenase. 20 of the total H+ combine immediately with nicotinamide adenine dinucleotide ( NAD+) which is a derivative of vitamin niacin. The free H+ and the H bound to NAD enter oxidative chemical reactions that form large quantities of ATP The remaining 4 H atoms are released during the step of succinic acid and fumaric acid stages, and combine to specific dehydrogenase but are not released to NAD+ They pass directly from dehydrogenase into the oxidative process Presentation title 23 Krebs cycle The cause of release of Co2 = through specific protein enzymes- decarboxylases They splitCo2 away from the substrate Co2 dissolves in the body fluids Transported to lungs Expelled from the body via the lungs Presentation title 24 Oxidative phosphorylat ion Presentation title 25 Oxidative phosphorylation Only small amounts of ATP formed during 1. Glycolysis 2. Citric acid cycle 3. Dehydrogenation 4. Decarboxylation The function of these earlier stages are to make H+ available for oxidation! 90% ATP is formed by oxidation of H+ atoms that were released during early stages of glucose degradation Oxidation of H+ is caused by a series of enzymatically catalysed reactions in mitochondria Presentation title 26 Oxidative phosphorylation These catalysed reactions: 1. Split each hydrogen atom into a H+ ion and an electron 2. Use the electron to combine dissolved oxygen (of fluids) with water molecules to form hydroxyl ions 3. Hydroxyl ions and hydrogen atoms combine to form water During the oxidative reactions a large amount of energy is released to form ATP THIS IS CALLED OXIDATIVE PHOSPHORYLATION, which occurs only in the mitochondria by a specialized process called the CHEMIOSMOTIC MECHANISM. Presentation title 27  Step 1 In oxidative phosphorylation: ionize hydrogen atoms that have been removed from food substrates H atoms are removed in pairs 1 H atom immediately becomes a hydrogen ion Other H atom combines with NAD+ to form NADH ( nicotinamide adenine dinucleotide) The H atom attached to NADH releases to form another H+, this process reconstitutes NAD+ to be used repeatedly Electrons removed from H atoms to cause H+, immediately enter the electron transport chain of electron acceptors, which form an important part of the inner mitochondrial membrane. Electron acceptors can be reduced or oxidised by accepting or giving up electrons Presentation title 28  Step 1 In oxidative phosphorylation: ionize hydrogen atoms that have been removed from food substrates Important members of electron transport chain (electron transporters): 1. Flavoprotein ( flavin mononucleotide) (FMN) 2. Iron sulfide proteins ( FeS) 3. Cytochromes B, C1, C, A, A3 Each electron is shuttled from one of these acceptors to the next until it finally reaches cytochrome A3 ( cytochrome oxidase) – called this because it is capable of giving up 2 electrons which in turn reduces the elemental oxygen to form ionic oxygen, which then combines with hydrogen to form water During the transport of the electrons, energy is released which causes the synthesis of ATP Presentation title 29 Step 2: the electron transport chain releases energy through the electron transport chain, which is used to pump H+ into outer chamber of mitochondrion 1. Electrons move through the electron transport chain 2. Large amounts energy are released 3. Energy is used to pump hydrogen ions from inner matrix of mitochondrion, to outer chamber ( between the inner and outer mitochondrial membranes 4. Process creates a high concentration of positively charged H+ in the chamber 5. Also creates a strong negative electron potential in the inner matrix Presentation title 30 Step 3: formation of ATP through the conversion of ADP into ATP Happens through large protein molecule which is a ATPase molecule called ATP synthetase. This molecule protrudes through the inner mitochondrial membrane and projects with a knoblike head into inner mitochondrial matrix The high concentration positive charged H+ in the outer chamber and large electrical potential difference across the membrane causes… H+ to flow into inner mitochondrial matrix through the substance of the ATPase molecule The energy derived from the H+ flow, is used by ATPase to convert ADP to ATP The conversion is caused by combining ADP with a phosphate radical (pi), which adds another high-energy phosphate bond to the molecule Presentation title 31 Step 4:Final step, to transfer ATP from inside mitochondria outside to the cell cytoplasm Occurs through facilitated diffusion Outward to the permeable outer mitochondrial membrane The ADP is continually transferred in the opposite direction ( to the inner membrane of mitochondria) for the continual conversion into ATP NB! For every 2 electrons that pass through the entire electron transport chain, up to 3 molecules of ATP is synthesized. Presentation title 32 Summary of ATP Formation during glucose breakdown 1. During glycolysis 4 molecules ATP is formed but 2ATP is used to cause phosphorylation of glucose. Net gain = 2ATP molecules 2. 1 mol ATP is formed during each revolution of the Krebs cycle, but each glucose molecule splits into 2 pyruvic acid molecules, which means that there are 2 revolutions of the cycle. Net gain = 2 ATP molecules 3. During entire schema of glucose breakdown, 24 H atoms are released. 20 of H atoms are oxidised in conjunction with the chemical osmotic mechanism (oxidative phosphorylation) with release of 3 ATP molecules per 2 H atoms metabolised. Net gain= 30 ATP molecules. 4. Remaining 4 H atoms are released by degydrogenase into the chemiosmotic oxidative schema. 2 ATP are released for every 2 H atoms. Net gain = 4 ATP Total of 38 ATP molecules are formed for each glucose molecule. Presentation title 33 Pentose phosphate pathway Second important mechanism for breakdown and oxidation of glucose Responsible for glucose breakdown in the liver and fat cells This pathway provides energy independently of all the enzymes of Krebs cycle, this implies that PPP is the alternative pathway for energy metabolism when enzyme abnormalities occur. Presentation title 34 Release of Co2 and H by the pentose phosphate pathway Glucose during several stages of conversion releases one molecule of CO2 and 4H atoms, this results in the formation of the 5-carbon sugar D-ribulose. This substance can change into 5,4,7,3 carbon sugars Various combinations of these sugars can resynthesize glucose Only 5 molecules of glucose can be resynthesized for every 6 molecules of glucose One molecule of glucose is resynthesized for each revolution of the cycle By repeating the cycle, all the glucose can eventually be converted into CO2 and H Presentation title 35 The H can enter the oxidative phosphorylation pathway to form The use of H to synthesize fat, the function of nicotinamide adenine dinucleotide phosphate H atom released during PPP does not combine to NAD+, but it combines to NADP+ ( nicotinamide adenine dinucleotide phosphate). This is important because only H combined with NADP+ to form NADPH can be used to synthesize fat from carbs. When glycolytic pathway becomes slowed ( because of cellular inactivity) the PPP remains operative ( in the liver) to break down excess glucose that continues to be transported into cells. NADPH becomes plentiful to help convert acetyl-CoA into long fatty acid chains This is another way in which energy in glucose molecules are used other than the formation of ATP, in this case it is used for the formation and storage of fat in the body Presentation title 36 Glucose conversion to glycogen or fat When glucose not immediately required for energy, extra glucose are stored as glycogen or converted into fat Glucose is preferably stored as glycogen until the cells have stored as much glycogen as they can ( amount sufficient to supply energy needs for 12-24 hours) Additional glucose is converted into fat in the liver and fat cells as fat, and is stored as fat in the fat cells. Presentation title 37 Pentose phosphate pathway for glucose metabolis m Presentation title 38 Effect of ADP and ATP cell concentrations in controlling Glycolysis and Glucose Oxidation Glycolysis and the oxidation of H atoms are controlled in accordance with the need of cells for ATP. Control I accomplished though several mechanisms, the most important of these mechanisms are the effects of cell concentrations of both ADP and ATP in controlling the rates of chemical reactions in the energy metabolism sequence. 1. ATP inhibits the enzyme phosphofructokinase. Because this enzyme promotes the formation of fructose-1,6-diphosphate, the net effect of excess cellular ATP is to slow/ stop glycolysis, which stops carbohydrate metabolism. DP causes the opposite change (increasing phosphofructokinase activity). When ATP is used by the cells, ADP concentration increases which increases the phosphofructokinase activity. The glycolytic process is set in motion, the total cellular store of ATP is replenished. Presentation title 39 Effect of ADP and ATP continued… 1. … 2. Citrate ion formed in citric acid cycle. An excess of this ion strongly inhibits phosphofructokinase, which prevents glycolytic processes from the citric acid’s ability to use the pyruvic acid formed during glycolysis. 3. If all the ADP in cells have already been converted to ATP, additional ATP cannot be formed. The entire sequence involved in using foodstuffs ( protein, fat, carbs) to form ATP is stopped. When ATP is used, ADP and AMP turn on the energy processes again, and are converted back to ATP. This concludes that a full storetitleof ATP is maintained. Presentation 40  Anaerobic release of energy Oxygen becomes unavailable/ unsufficient Oxidative phosphorylation cannot take place Small amount of energy can still be released by cells by the glycolysis stage of carb degradation This is because the chemical reactions for the breakdown of glucose into pyruvic acid do not require oxygen, this is a very wastefull process but This release of glycolytic energy can be a lifesaving measure when oxygen becomes unavailable Presentation title 41 Outcome 5: the formation of lactic acid during anaerobic glycolysis allows release of extra anaerobic energy Law of mass action states that if the end products build up in a medium, the rate of the reaction will decrease. The two end products ( pyruvic acid and H atoms) The buildup of either or both of these products would stop the glycolytic processes and prevent further formation of ATP When their quantities are in excess, these two products react with each other to form lactic acid Under anaerobic conditions, most of pyruvic acid is converted into lactic acid. Lactic acid then diffuses out of the cells into the extracellular fluids and into intracellular fluids of other less active cells Lactic acid is like a sink hole where to excess glycolytic products can disappear and this allows Presentation title 42 glycolysis to proceed longer than it would have. Reconversion of lactic acid to pyruvic acid when oxygen becomes available again When person breathes oxygen again after anaerobic metabolism, lactic acid is converted back to pyruvic acid and NADH plus H+. Large portions of these substances are oxidised to form large quantities of ATP Excess ATP then causes rest of pyruvic acid to be converted back to glucose The large amount of lactic acid created is thus not lost from the body because the lactic acid can be converted to glucose or used directly for energy Presentation title 43 Use of lactic acid by the heart for energy Heart muscles can convert lactic acid to pyruvic acid and use it for energy This process happens during heavy exercise When large amounts of lactic acid is released into the blood from skeletal muscles and consumed as extra energy source by the heart Presentation title 44 Outcome 6: gluconeogenesis- the formation of carbohydrates from proteins and fats When carb stores of the body decreases below normal, glucose can be formed from amino acids and glycerol portion of fat This is called gluconeogenesis This process is important in preventing excessive reductions in blood glucose concentrations during fasting. Glucose is primary substrate for energy in the brain, red blood cells, adequate amounts of glucose must be present in the blood for several hours between meals The liver is important in maintaining the blood glucose levels, because it converts stored glycogen into glucose, and by synthesizing glucose from lactate and amino acids 25% liver glucose production is from gluconeogenesis, which provides a steady supply of glucose to the brain During long fasting periods, the kidneys synthesize glucose from amino acids 60% amino acids in body proteins can be converted to carbohydrates. Rest 40% have difficult structures. Presentation title 45 gluconeogenesis- the formation of carbohydrates from proteins and fats Each amino acid is converted into glucose by slightly different chemical processes. Ex- alanine is converted directly to pyruvic acid by deamination, the pyruvic acid can then be converted into glucose or stored glycogen. The more complicated amino acids can be converted to 3,4,5,7 carbon sugars, they can then enter the phosphogluconate pathway and form glucose. Summary: by means of deamination and several simple interconversions, many of the amino acids can become glucose Presentation title 46 Regulation of gluconeogenesis Stimuli for gluconeogenesis 1. Diminished carbohydrates in cells 2. Decreased blood sugar levels The diminished carbohydrates can reverse many of the glycolytic and phosphogluconate reactions This allows the conversion of amino acids and glycerol into carbohydrates Hormone cortisol is important in this regulation Presentation title 47 Effect of adrenocorticotropic hormone and glucocorticoids on gluconeogenesis When carbs are not available to the cells, the adenohypophysis secretes increased quantities of adrenocorticotropic hormone ( ACTH) This stimulates the adrenal cortex to secrete cortisol Cortisol mobilises proteins from all cells of the body, making them available in the form of amino acids in the body fluids Big portion of these amino acids become deaminated in the liver, and provides ideal substrates for conversion into glucose One of the most important ways in which gluconeogenesis is promoted, is by the release of glucocorticoids from the adrenal cortex Presentation title 48 Blood glucose Normal blood glucose concentration of a person who has fasted for 3-4 hours is 90mg/dl After high carb meal the level reaches above 140mg/dl (except for person with diabetes mellitus ) Regulation of blood glucose is related to the pancreatic hormones insulin (decreases) and glucagon ( increases). Presentation title 49 good luck