IPHY 3470: Week 3 - Lecture 6
IPHY 3470: Week 3 - Lecture 6 IPHY 3470
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This 4 page Class Notes was uploaded by Sydney Lazzell on Thursday September 8, 2016. The Class Notes belongs to IPHY 3470 at University of Colorado at Boulder taught by Christopher DeSouza in Fall 2016. Since its upload, it has received 17 views. For similar materials see Human Physiology 1 in integrated physiology at University of Colorado at Boulder.
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Date Created: 09/08/16
IPHY 3470: Human Physiology 1 Week 3 – Lecture 6 Chalk Talk CHO Metabolism o Normal glucose: 70-100 mg/dL o Uptake of glucose: 1. Type of tissue 2. Level of glucose in blood/tissue 3. Presence of insulin 4. Physiological state of tissue o Largest glucose consuming tissue = muscle o Lots of glucose = nerve & brain Glycolysis o Glucose à 2 ATP à 2 Pyruvate/2 Lactate o NAD recycles to step 6 in anaerobic metabolism (pyruvate à lactate) o HK, PFK, PK are the most important enzymes (step 1,3,10) o They can only go in one direction (downward); all other enzymes can go in both directions Step 1: ATP ADP + H Glucose Glucose 6 Phosphate (G-6-P) o Enzyme = hexokinase (1 rate limiting step) Step 2: G-6-P Fructose 6 Phosphate o Enzyme = phosphohexoisomerase Step 3: ATP ADP + H F-6-P F1,6DP o Enzyme = PFK (2 rate limiting enzyme) Step 4: F1,6DP G3P & Dihydroxyacetone phosphate o Enzyme = aldolase Step 5: G3P Dihydroxyacetone phosphate o Enzyme = triose isomerase Step 6: NAD + Pi NADH + H2O G3P 1,3 –DPG o Enzyme = GAPDH o First “high energy” intermediate formation (NADH) o Used for lactate production or shuttles electrons o No NAD = glycolysis shuts down Step 7: ADP + H ATP 1,3- DPG 3-PG o Enzyme = phosphoglycerate kinase o First ATP generation Step 8: 3-PG 2-PG o Enzyme = phosphoglyceromutase Step 9: H2O 2-PG PEP o Enzyme = enolase Step 10: ADP + Pi ATP PEP Pyruvate o Enzyme = pyruvate kinase (3 rate limiting enzyme) o End of glycolysis o Pyruvate à lactate; enzyme = LDH Lecture Slides Glycolytic Flux o Flux = rate of flow of intermediates through metabolic pathway o Flux through flux generating step vary in response to organisms metabolic requirements o Change in flux is communicated throughout the pathway o For glycolysis the primary rate determining step is: o Step 3: F-6-P à F1, 6DP Enzyme = PFK Factors that effect flux o Factors #1-3 are fast; factor #4 is much slower 1. Allosteric control: many enzymes are regulated by effectors such as substrates, products, or coenzymes (e.g. PFK) a. PFK is activated by: ADP, AMP, F-6-P (low levels of ATP) b. PFK is inhibited by: ATP, citrate, fatty acids c. In muscle tissue PFK is a major control point for glycolysis d. When ATP is high as a result of low metabolic demand, PFK is inhibited & flux through pathway is low e. When ATP is low, flux through pathways is high to replenish ATP 2. Covalent modification: many enzymes have specific sites that may be enzymatically phosphorylated or dephosphorylated or covalently modified (increase or decrease activity) 3. Substrate activity: opposing nonequilibrium reactions catalyzed by different enzymes may be independently varied – balance between 2 enzymes (to go in different directions) a. HK: reverse G-6-phosphatase : inhibit G-6-P b. PFK: reverse FB phosphatase : inhibit ATP c. PK: reverse pyruvate carboxylase : inhibit ATP 4. Genetic control: enzyme concentrations & activity may be altered by protein synthesis in response to protein needs Summary o Aerobic = pyruvate formed is further oxidized by citric acid cycle & oxidative phosphorylation (à goes to mitochondria) o Anaerobic = pyruvate always goes to lactate (at high intensity) o 1 NADH = 3 ATP; net from 1 glucose = 38 ATP o Aerobic metabolism is slower than anaerobic (more steps) Glycogenolysis, Gluconeogensis, Mitochondria and Krebs Cycle o Muscle is NOT gluconeogenic ; but the liver is o Muscle is gluco-utilizing o Glycogenolysis = storage form of CHO in body is glycogen o Liver & muscle storage tissues for glycogen o Muscle breakdown glucose for ATP; liver breakdown for production o Muscle glycogen used to synthesize ATP during muscle contraction (glycolysis) § Liver glycogen is used to maintain blood levels during periods of low blood glucose (e.g. fasting/starving) § Always want to maintain blood glucose levels o
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