Glycolysis and Gluconeogenesis Carbohydrate Regulation PowerPoint 2
Glycolysis and Gluconeogenesis Carbohydrate Regulation PowerPoint 2 NUTR 4550
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This 7 page Class Notes was uploaded by Victoria Hills on Monday January 25, 2016. The Class Notes belongs to NUTR 4550 at Clemson University taught by Dr. Elliot Jesch in Spring 2016. Since its upload, it has received 65 views. For similar materials see Nutrition and Metabolism in Nutrition and Food Sciences at Clemson University.
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Date Created: 01/25/16
Clemson University Spring 2016 Nutrition and Metabolism NUTR 4550 Unit 1 Regulation Carbohydrate PowerPoint 2 1112016 Slide 1 Figure 128 Figure 128 is showing glycolysis on the left side and gluconeogenesis on the right side their corresponding regulatory factors First regulated step in glycolysis Glucose 9 Glucose6Phosphate via glucokinasehexokinase Points of regulation a Insulin 0 Up regulates glucokinasehexokinase o Increases the concentration number of glucokinaseshexokinases in order for glucose to be phosphorylated to be glucose6phosphate 0 When carbohydrates Such as glucose or fructose are more quickly phosphorylated more uptake of the carbohydrates is able to enter the cell b FructoselPhosphate 0 Up regulates glucokinasehexokinase via increasing its activity 0 Fructose1phosphate comes from fructose and is one of the pathways that fructose is able to enter glycolysis c Fructose6Phosphate 0 Down regulates Inhibits glucokinasehexokinase when large amounts of fructose6phosphate are present from the step where glucose6phosphate 9 fructose6phosphate 0 Down regulates glucokinasehexokinase in preparation for the next 3 step in glycolysis where fructose6phosphate 9 fructose16bisphosphate via P6FK1 because fructose6 phosphate is acting at this point as a precursor to this reaction fructose6phosphate 9 fructose16bisphosphate for regulation in order not to overwhelm the rest of glycolysis This is known as feed back regulation 0 Feed back regulation Where a product of a reaction will feed back to the previous reaction 9 Here A lot of fructose6 phosphate will down regulate glucokinasehexokinase activity Second regulated step in glycolysis Fructose6Phosphate 9 Fructose16Bisphosphate via P6FK1 Phosphofructokinase Points of regulation a ATP 0 Down regulates PFK 0 Down regulates PFK because the cell has enough ATP so it is unnecessary to continue shuttling glucose other monosaccharides in to produce more ATP 0 Key to note that ATP will not shut down this pathway but instead the monosaccharides will continue to go through glycolysis 9 Pyruvate 9 Acetyl CoA in order to enter fatty acid synthesis instead of continuing through the TCA cycle and electron transport chain 0 In general ATP production is slowed down by heavy ATP presence in the cell b Hydrogen Protons 0 Down regulates glucokinasehexokinase o The protons are being referred to their place in the electron transport chain when they are being pumped into the inner mitochondrial space that creates the chemiosmotic gradient used to make ATP with ATP synthase 0 If the concentration of protons is sustained though this means that the cell is signaling that there are enough reducing equivalents providing the protons so that the TCA cycle and glycolysis should slow down as a result c AMP Pi Inorganic phosphate 0 Up regulate PFK 0 When there is increased AMP and Pi present in the cell the cell is sensing that it is currently using energy ATP 0 Therefore it is necessary to continue having more of a ow of glucose into the cell through the glycolytic pathway d Citrate Indirectly 0 Down regulates slows down PFK o Citrate is a TCA cycle intermediate that is formed when oxaloacetate and acetyl CoA are combined 0 As citrate circles back around to oxaloacetate in the full TCA cycle therea re 4 dehydrogenase enzymes that are producing reducing equivalents that will be shuttled to the electron transport chain to donate their electrons for the chemiosmotic gradient and ultimately ATP production through ATP synthase 0 A buildup of citrate is indicating that the electron transport chain has enough protons and therefore ATP in the cell Citrate is the stopping point as a result 0 Further a buildup of citrate tells glycolysis in the cytoplasm that glucose and other monosaccharides do not need to be broken down at this point e Insulin 0 Up regulates 6PFK1 o Increases fructose26bisphosphate Metabolite and its enzyme 6PF2K This enzyme phosphorylates the second carbon of fructose6phosphate 9 This is a shunt pathway in glycolysis Fructose26bisphosphate is an allosteric regulator of 6PFK1 Allosteric regulator definition A metabolite that binds to a protein and modifies that protein to increase or decrease its activity The cell sense the presence of insulin so that the enzyme for fructose26bisphosphate increases which tells the cell to produce more 6PF1K to allow more glucose to ow through the glycolytic pathway and have more of rapid conversion from fructose6phosphate 9 fructose16bisphosphate Overall Fructose26Bisphosphate acts upon 6PF1K as a result An allosteric regulator of 6PF1K so molecule will bind or interact with 6PF1K to increase its activity NOT concentration so allows for more rapid conversion from F6P to F16BisP 0 Third regulated step in glycolysis PEP Phosphoenolpyruvate 9 Pyruvate via pyruvate kinase Points of regulation a ATP 0 Down regulates pyruvate kinase activity 0 Sensing that the cell has enough energy at this point b Alanine 0 Down regulates pyruvate kinase 0 Pyruvate is the alpha keto acid of alanine Alanine is deaminated or transaminated with the removal of NH3 to produce pyruvate 0 Therefore a lot of glucose is not needed when there is a lot of O O alanine around Alanine is abundant when eating protein sources GlucoseAlanine Cycle Occurs when there is an attempt to make glucose from peripheral tissues so that pyruvate 9 alanine 9 liver 9 gluconeogenesis which slows down the glycolytic pathway Alanine up regulates gluconeogenesis c Glucagon O O 0 Down regulates pyruvate kinase Signals for the release of glucose into the blood stream Signals for the breakdown of glycogen and up regulates gluconeogenesis Inhibits pyruvate kinase Insulin levels are low when glucagon is present therefore it is not necessary to have more products going through the glycolytic pathway when glucose is needed in the blood When the liver senses glucagon it will start breaking down glycogen Muscle and liver and initiating gluconeogenesis Liver and little occurs in the kidneys to breakdown to get free glucose d Epinephrine 0 Down regulates pyruvate kinase 0 Fight or ight hormone o Inhibits pyruvate kinase 0 Increases FA catabolism e Fructose16bisphosphate 0 Up regulates pyruvate kinase 0 Product of PFKl so signals the up regulation of pyruvate kinase because if the cell is signaling for more PFK1 enzymes to be produced it wouldn t make sense to down regulate its follow up metabolism later in the glycolytic pathway 0 This is known as feed forward regulation Here it s necessary to up regulate pyruvate kinase to ensure that fructose16 bisphosphate ends up at the end of the metabolic pathway 0 Feed forward regulation When a compound regulates another reaction further down a pathway f Insulin 0 Up regulates pyruvate kinase 0 Facilitates posttranslational modifications where enzymes will be phosphorylated or de phosphorylated to either increase or reduce the activity of that enzyme 0 With pyruvate kinase insulin increases it via de phosphorylation The prime difference between glycolysis and gluconeogenesis are the enzymes for the regulated steps 9 Even though most of gluconeogenesis is the reverse of glycolysis it s important for there to be different enzymes so that there won t be a ow of molecules going through one of the pathways at the same time as the ow of molecules going through the other pathway Inefficient First regulated step in gluconeogenesis Pyruvate 9 oxaloacetate via pyruvate carboxylase Points of Regulation a Acetyl CoA 0 Up regulates pyruvate carboxylase 0 When one is consuming and using FA as an energy source beta oxidation must occur which produces much acetyl CoA o In order to use acetyl CoA oxaloacetate must be used to combine with acetyl CoA to form citrate in the TCA cycle 0 Running out of oxaloacetate is a concern since there is so much acetyl CoA production from beta oxidation because then the TCA cycle won t continue to run 0 Ovearall Pyruvate 9 oxaloacetate via pyruvate carboxylase partly for TCA cycle in the production of energy and in gluconeogenesis to make glucose since pyruvate is unable to go back to PEP Oxaloacetate is able to be converted to PEP Second regulated step in gluconeogenesis Oxaloacetate 9 PEP via PEP carboxykinase Points of Regulation a Insulin 0 Down regulates PEP carboxykinase 0 When the liver or kidney senses insulin there is a decrease in the concentration of PEP carboxykinase o The ubiquitin proteosomal pathway is used to decrease the number of PEP carboxykinases by degrading the enzymes and returning their AA parts to the AA pool 0 Third regulated step in gluconeogenesis Fructose16bisphosphate 9 Fructose6Phosphate via fructose 16bisphosphatase Points of Regulation a Fructose26bisphosphate 0 Down regulates fructose16bisphosphatase because ample product is owing through glycolysis b AMP 0 Down regulates fructose16bisphosphatase because it is signaling for an increase in PFK in glycolysis since the cell needs energy Fourth regulated step in gluconeogenesis Glucose6Phosphate 9 Glucose via glucose6phosphatase Occurs in the liver and kidney only Points of Regulation a Insulin 0 Down regulates glucose6phosphatase Liver specifics Glucose is taken up by the liver through GLUT 2 and uses purely facilitated diffusion 9 free glucose fructose in the cell As free glucose comes into the cell it s important to phosphorylate glucose because a high concentration of free glucose will slow down the glucose uptake So phosphorylating glucose or any other carbohydrate will increase the amount of glucose taken up by the cell Fructose is able to enter as fructose1phosphate or predominantly as fructose6phosphate via glucokinase Liver wants to take up as much carbohydrate as possible because it s going to break it down to pyruvate for ATP production First or it is going to store the glucose as glycogen or FAtriglyceride Not all tissues are able to do this 9 This all occurs especially in the liver to make the body as efficient as possible Slide 2 Figure 129 In the top left of the figure Shows how glucose is entering the liver cell through GLUT 2 and how glucokinase is phosphorylating glucose 9 glucose 6phosphate which occurs primarily in the fed state In the top right of the figure Shows how in the endoplasmic reticulum ER there is an inorganic phosphate transporter glucose6phosphatase and a different glucose transporter for the ER facilitating the reverse process of reproducing glucose from glucose6phosphate The reverse process of producing glucose from glucose6phosphate in the cell occurs during times in the fasted state Fasted State Glycogen is broken down to glucose6phosphate 9 glucose 0 Glucose6phosphate that is produced in the cytoplasm from the breakdown of glycogen 9 ER where glucose phosphatase converts glucose6phosphate 9 glucose inorganic phosphate Lactate 9 glucose6phosphate via gluconeogenesis process that must go through the ER as well 0 Other tissues and red blood cells generate lactate mainly because NAD must be regenerated as an electron acceptor in glycolysis involving the step from glyceraldehyde3phosphate 9 13 bisphosphoglycerate o Skeletal muscle generates lactate because of the lack of oxygen in high intensity movement The lactate is transported back to the liver to go through gluconeogenesis After glucose has been regenerated from glucose6phosphate in the ER the glucose transporter T3 takes the free glucose to the membrane of the ER where GLUT 2 picks the glucose up and takes it to the cellular membrane to be released back into the blood stream to maintain blood glucose concentrations Inorganic phosphate also has its own transporter in the ER so it can be reused for phosphorylation of other incoming glucose in fed state times Slide 3 Figure 1210 Slight review of previously discussed concepts Top portion of the figure A Insulin is present Fed state Insulin signals cell to take up glucose 9 glycolysis Specially showing the point where glucose 99 fructose6phosphate 9 Fructose16bisphophate via 6PFK1 Step 3 Insulin up regulates this enzyme Serine residue of 6PF2K and insulin 9 Shunted Pathway 0 Within 6PF2K there is a specific serine residue that is de phosphorylated when insulin is secreted which leads to the active form of 6PF2K that generates fructose26bisphophate from fructose6phosphate that up regulates 6PF1K so more glucose 9 pyruvate 0 Bottom portion of the figure B Glucagon and epinephrine are present Fasted state Pancreas has secreted glucagon to signal cells to break down glucose for energy Figure shows how pyruvate 9 oxaloacetate 9 PEP 9 fructose16 bisphosphate 9 fructose6phosphate Via fructose16bisphosphatase Part of the steps for gluconeogenesis discussed here Serine residue of 6PF2K and glucagon o Fructose26bisphophate is decreased in amount being produced because the serine residue of 6PF2K is phosphorylated 9 down regulation of 6PF1K and up regulation of fructose26phosphatase 9 fructose6phosphate Therefore overall gluconeogenesis is up regulated eventually get back to free glucose that can be used by tissues in the body Especially red blood cells and the brain first
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