Pyruvate Metabolism Metabolism Exam 2 We all know there are 4 things that can go through gluconeogensis in order to be converted into energy Those things consist of amino acids glycerol lactate and pyruvate We will be discussing pyruvate metabolism There are 3 forms of potential energy sources for gluconeogensis pyruvate metabolism All three are reversible 1 Amino acid alanine 2 Glucose 3 Lactate After being converted into pyruvate 3C molecule they can use the enzyme pyruvate dehydrogenase PDH to convert into Acetyl CoA 2 C molecule CO2 This process is an example of a oxidative decarboxylation of an alpha ketoacid amino acid without amine group The irreversible process occurs in the mitchondria The PDH enzyme step generate NADH H Also cofactors TPP FAD CoASH are formed explained later PDH is insulin favord as it is requires a dephosphorylation to be activated o Inhibited by Starvation uncontrolled diabetes and endurance exercise Increased NADH H Increased Acetyl Coa Increased ATP o Favored by Conditions that favor fat synthesis Acetyl CoA is the common intermediate for synthesis of TAG Increased Insulin in the adipose tissue Tricarboxylic TCA Cycle also known as Citric Acid or Krebs Cycle This process requires O2 and is in the mitochondria and represents a common metabolic pathway o Proteins that are converted to amino acids to enter the cycle can either be converted to pyruvate or Acetyl CoA TCA cycle Pyruvate amino acid is glucogenic Acetyl CoA amino acid is Ketogenic When Acetyl Coa is entering the TCA cycle it binds to Oxaloacetate OAA which requires Citrate Synthase to generate Citrate Coenzyme A CoASH This process has an importance to regenerate OAA and 2 CO2 are formed o Citrate important for fatty acid synthesis is converted to Isocitrate with the enzyme Aconitase This is a 2 step process 1 Citrate Cis asconitate dehydration 2 Cis asconitate Isocitrate hydration Isocitrate alpha Ketoglutarate glutamate o Isocitrate dehydrogenase is the enzyme used o NADH H is generated o CO2 is released Alpha ketoglutarate Succinyl CoA Heme o Alpha ketoglutarate Dehydrogenase TPP FAD o CoASH enters to make the CoA on Succinyl o NADH H is generated o 2nd CO2 released o This is an oxidative decarboxylation of an alpha ketoacid Succinyl CoA Succinate o Succinic Thiokinase is the enzyme o GTP ATP produced substrate level phosphorylation o CoASH released Succinate Fumarate o Succinate Dehydrogenase o FADH2 only step where FAD is used Fumarate Malate o Fumerase o H20 enters hydration Malate OAA pyrimidines or glucose o Malate Dehydrogenase o NADH H o This is where the cycle can continue to repeat itself Energetics o 12 ATP produced from TCA cycle and all starts from molecule Acetyl CoA 9 from NADH H 1 from GTP 2 from FADH2 o 15 ATP if you begin with Pyruvate 12 from NADH H 1 from GTP 2 from FADH2 o If you are using one molecule of glucose you end with 38 ATP and 4 CO2 2 ATP from glycolosis 4 NADH from glycolosis and 6 from Krebb cycle 2 FADH from krebb cycle 2 GTP from Krebb cycle When you create energy from NADH H and FADH2 you are using the H s and transporting them to ETC shuttle systems in the mitochondria o Malate shuttle For H s to end up in the mitochondria the H s from NADH H attach to OAA OAA goes to malate so that it can go through the membrane Then malate goes back to OAA and gives H s to NAD in the mitochondria There is no energy being used H s end up on NAD to form NADH H Active in the liver kidney and heart 3 ATP can be formed o Glycerol 3 PO4 NAD as cofactor in cytoplasm and FAD in the mitochondria So H s are taken from NAD and given to FAD There is an energy change since it is the mitochondrial membrane so lose 2 ATP 38 ATP 2ATP 36 net ATP 37 if from muscle and hexokinase is not needed H s end up attached to FAD to form FADH2 Active in muscle and brain 2 ATP formed The rate limiting enzymes are o Citrate Synthase o Isocitrate dehydrogenase o Alpha ketoglutarate dehydrogenase Inhibition by accumulation products o NADH H Inhibits dehydrogenase o Citrate Blocks citrate synthesis o ATP inhibits citrate cynthase and isocitrate o Succinyl CoA inhibts alphaketoglutarate dehydrogenase and citrate synthase Electron Transport Chain accomplished in the mitochondria The purpose is to capture energy in the form of ATP by coupling the two processes of oxidation and phosphorylation o Oxidation loss of of H s NADH2 NAD o Phosphorylation addition of phosphorus ADP ATP o Uncoupling This term corresponds to protein producing heat not energy An important tissue for this is Brown eyed tissue Proton Pumps o There are 4 complexes which remove electrons from coenzymes located in the inner mitochondria space and or pump protons into the outer membrane space 1 NADH Q oxidoreductase 2 Succinate Q reductase 3 Cytoochrome C oxidoreductase 4 Cytochrome c oxidase Electron Transporters o Transports between complexes in the ETC Ubiquinone Coenzyme Q Transports between complex 1 and 3 and 2 and 3 Cytochrome C Transports electrons between 3 and 4 ATP synthase Transports protons across the inner mitochondrial membrane for phosphorylation of ADP ATP During H pump o During the transfer of electrons oxidation energy is released o This energy can be used to pump protons into the inner membrane space creating a gradient o When the gradient is diffused as protons flow back into the matrix this energy can be used to make ATP if the protons are diffused back through ATP synthase o Looking at the last chart on this slide set the 4 4 2 H s that are pumped from complexes 1 3 and 4 are pumped into the innermembrane space They enter ATP synthase complex The ATP synthase has 2 subunits F0 and F1 F0 allows for the H s to move in and F1 to allow for phosphorylation The 4th complex only allows 2 H s instead of 4 because 2 H s are used with O2 to generate H20 The electrons from 1 3 and 2 3 are accepted by Coenzyme Q and are accepted at complex 4 by Cyt C Fructose and Galactose Metabolism Fructose and Galactose can both be converted to glucose and phosphorylated in the liver and then can be used to produce energy o After becoming glucose it can attach to GLUT 2 in the blood The main reason that they need to be converted to glucose is because the Km is much lower for glucose than fructose or galactose o Liver glucokinase fructokinase galactokinase phosphrylation enzymes are most favorable here in the liver o Muscle hexokinase Very low affinity for fructose and galactose meaning a very high Km Fructose metabolism o Fructose F 1 P
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