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TAMU NUTR 470 - Nutritional Regulation of Glycolysis
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NUTR 470 1st Edition Lecture 4Current Lecture-Nutritional Regulation of Glycolysis• Not just know the pathway, but these steps are based on nutrition condition (fast or feeding)-two signals: glucose and insulin in response to feeding -these signals generate the effects that allow the pathways to begin • First transporter for uptake, then enzyme for phosphorylation• phosphorylation starts the first step of glycolysis• Glucose uptake is allowed by GLUT4 coming to the surface and up-taking glucose; then phosphorylation is the rate limiting step• without enough oxygen, pyruvate turns into lactate• In the liver, the NET outcome of glucose fluxes determines glucose production, and therebyplasma levels of glucose-Physiological Role of Glycolysis• Glycolysis is the simplest glucose metabolic flux• Glycolysis is crucial for the regulation of glucose homeostasis.• Glycolysis provides immediate energy-particularly for the neurons. -Needed for sprints• Glycolysis is associated with many biological functions-insulin secretion -Glycolysis• Step one: -HK/GK catalyze the phosphorylation of glucose as the first step of glycolysis• Step two-6PFK1 catalyzes the rate-limiting step of glycolysis• Step 3-F-2,6-P2 is the most powerful activator of 6PFK1• step 4These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-ATP is generated at two steps of glycolysis• Fructose-6P—>Fructose 1,6P2 is the rate determining step and is catalyzed by 6pfk1-this is the most powerful activator for this enzyme-how does this affect Km/Vmax? smaller Km, increase of Vmax • Glyceraldehyde-3-P is generated and in excess will provide the backbone for lipids and create double the energy stored-Glycolysis and Glucose Homeostasis• Glycolysis is crucial for glucose homeostasis• Glycolysis in the liver-The liver produces glucose. Rates of glycolysis in the liver determine the amount of glucose been produced.• Glycolysis in pancreatic islet beta cells• Glycolysis is coupled to glucose-stimulated insulin secretion.-Glucose phosphorylation is the first step of glycolysis• Hexokinase II— HKII determines glucose phosphorylation in many tissues other than liver and pancreatic islet beta cells.• Glucokinase— determines rates of glycolysis in liver cells.-Glucokinase is crucial for the regulation of glucose-stimulated insulin secretion.• helps the liver turn glucose from production to storage-Glucokinase is a therapeutic target of diabetes.• powerful enough to treat diabetes, but actually too powerful to actually use-Fate of Glucose-6-phosphate• Glycolysis-Generation of fructose-6-phosphate• Glycogen synthesis-Direct pathway of glycogen synthesis• Pentose phosphate shunt-Generation of NAPDH-important for lipogenesis• Glucose cycling-Glucose production from the liver-Generation of Fructose-1,6-bisphosphate• Generation of fructose-1,6-bisphosphate is a rate-limiting step of glycolysis• Enzyme-6-phosphofructo-1-kinase-kinase is the function; phosphofruct is the substrate• Reaction-F-6-P → Fructose-1,6-bisphosphate-transferase transferring phosphate to the one position-the kinase catalyzes this reaction -6-phosphofructo-1-kinase -catalyzes the rate-limiting step of glycolysis.— this is controlled by activators• Activator-Fructose-2,6-bisphosphate — the most powerful activator! (2 point question)-AMP• Inhibitor— increases KM bigger, Vmax smaller-ATP, Citrate-The Role of Fructose-2,6-bisphosphate• Fructose-2,6-bisphosphate is the most powerful activator of 6-phosphofructo-1-kinase.— this enzyme controls the rate limiting step. IMPORTANT!• Enzyme-6-phosphofructo-2-kinase• Reaction-F-6-P → Fructose-2,6-bisphosphate• Bisphosphatase-when fasting liver produces glucose over 90%. Why liver and not other organ? -Because the last step of glucose production we produced fructose-6-phosphate. F6P catalyzes the hydrolysis.-Similarly the phosphase that removes phosphate. so we have 2,6 position, and at the 2 position the phosphorous is removed converted back F6P.• Bi-function enzymes— two functions in one enzyme, there are only 5 enzymes that are bi-function-Feeding• Kinase → bisphosphate• One kinase adds a phosphate, two kinase adds another• in control of nutrition condition• glucose and insulin make the enzyme active and see increase in glycolysis• Protein phosphatase removes phosphate -Fasting• no glucose signal, so must switch to glucagon signaling• cAMP/PKA are part of the signaling cascade• Protein Kinase transfers phosphate to use • remove phosphate at the two position and see a decreasing the F2,6P2. Since this is the most powerful activator of 6pf1k, it is not produced.-instead FBPase is produced-Substrate-level of Phosphorylation• A reaction that results in the formation of ATP by the direct transfer of a phosphate group toADP from a reactive intermediate.• Phosphoglycerate kinase-1,3-bisphosphoglycerate → 3-phosphoglycerate• Pyruvate kinase-Phosphoenolpyruvate → pyruvate-The Fate of Pyruvate• Anaerobic conditions-Generation of lactate by lactate dehydrogenase (LDH)• Oxidation of pyruvate-Generation of acetyl-CoA by pyruvate dehydrogenase (PDH) complex-Regulation of Glycolysis: Role of Glucose• Glucose, serving as an important nutritional signal, is crucial for the regulation of glycolysis.• Effect on GK-Glucose induces the translocation of GK from nucleus to cytosol• more glucose (substrate), more enzyme, more glycolysis-increases GK activity—> which increases Glycolysis-the site of glycolysis is the cytosol-Regulation of Glycolysis: Role of Glucose-Glucose, serving as an important nutritional signal, is crucial for the regulation of glycolysis.-Effect on 6PFK2• Glucose induces/maintains the de-phosphorylation of 6PFK2• increase of Frutose-2,6-bisphosphate (which increases 6-phosphofructo-1-kinase because its the activator for it, so..) —> increases Glycolysis-De-phosphorylation• #1— PP (protein phosphatase)**• maintains de-phosphorylation in response to glucose signals-glucose maintains dephosphorylation-*will talk about 5 examples, need to know 2** this is the first example-Effect of gene expression— glucose metabolism promotes the expression of glucokinase• increase gene expression• glucose is crucial for secretion of pancreatic islet hormones-Regulation of Glycolysis: Role of Insulin•


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TAMU NUTR 470 - Nutritional Regulation of Glycolysis

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