Glycolysis Notes PDF

1- List and discuss reaction steps of glycolysis 2- Define aerobic & anaerobic types of glycolysis & list the importance of each 3- type & the differences between both Describe regulation of glycolysis  Glycolysis It means oxidation of glucose to give pyruvate (in t...

1- List and discuss reaction steps of glycolysis 2- Define aerobic & anaerobic types of glycolysis & list the importance of each 3- type & the differences between both Describe regulation of glycolysis  Glycolysis It means oxidation of glucose to give pyruvate (in the presence of oxygen) or lactate in the absence of oxygen. Site (cytoplasm of all tissue cells). It is of physiological importance in tissues of no mitochondria: mature RBCs,  Glycolysis: Specific tissue functions RBC’s Rely exclusively for energy Skeletal muscle Source of energy during exercise, particularly high intensity exercise Adipose tissue Source of glycerol-P for TG synthesis Source of acetyl-CoA for FA synthesis Liver Source of acetyl-CoA for FA synthesis Source of glycerol-P for TG synthesis ATP yield in glycolysis  glucose Glycolysis ATP Hexokinase ADP glucose-6-phosphate Phosphoglucose Isomerase fructose-6-phosphate ATP Phosphofructokinase ADP fructose-1,6-bisphosphate Aldolase glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate Triosephosphate Isomerase Glycolysis continued  glyceraldehyde-3-phosphate NAD+ + Pi Glyceraldehyde-3-phosphate NADH + H+ Dehydrogenase 1,3-bisphosphoglycerate ADP Phosphoglycerate Kinase ATP 3-phosphoglycerate Phosphoglycerate Mutase 2-phosphoglycerate H2O Enolase phosphoenolpyruvate ADP Pyruvate Kinase ATP pyruvate  ATP production of Glycolysis:- ATP production = ATP produced – ATP utilized ATP produced ATP utilized Net energy In the absence of 4 ATP( Substrate 2 ATP 2 ATP oxygen level From glucose to (anaerobic phosphorylation) glucose-6- p. Glycolysis) From fructose-6- p to fructose 1,6p. In the presence 4 ATP( Substrate 2 ATP 8 ATP of oxygen level From glucose to (aerobic phosphorylation) glucose-6- p. Glycolysis) From fructose-6- + 4 ATP or 6 ATP p to fructose ) from oxidation 1,6p. of NADH+H in mitochondria) Differences between glucokinase and hexokinase Glucokinase Hexokinase Site Liver cells only All tissues Substrate Glucose only Hexoses Insulin Stimulated No effect Affinity Low (high Km) High (low Km) G-6P No effect Inhibited Glucose Acts over 100 Acts on low glucose level mg% level  Difference between Aerobic and Anerobic Glycolysis. Aerobic Anaerobic End Product Pyruvate Lactate Energy 8 ATP 2 ATP Regeneration Through Through of NAD+ respiratory lactate chain in formation mitochondria  Biological importance of Glycolysis 1- Energy production: A- Anaerobic glycolysis gives 2 ATP. B- Aerobic glycolysis gives 8 ATP 2- Oxygenation of tissues: Through formation of 2,3 bisphosphoglycerate which decreases the affinity of HB to O2. 3- Provides important intermediates: 3 phosphoglcerate which gives amino acid serine. 4- Aerobic glycolysis provide the mitochondria with pyruvate which gives acetyl CoA Kreb’s cycle  Pyruvate Alcohol Anaerobic Fermentation Glycolysis Aerobic Glycolysis -Pyruvate can be further processed: a) anaerobically to lactate in muscle, RBCs and in certain micro-organisms or b) anaerobically to ethanol (fermentation) or c) aerobically to CO2 and H2O via the citric acid cycle. #LDH determination in hemolysed samples  Glyceraldehyde-3-phosphate Dehydrogenase H O + H+ O OPO32− 1C NAD+ NADH 1C Fermentation: + Pi H C OH H C OH 2 2 2− 2− Anaerobic 3 CH2OPO3 3CH2OPO3 organisms lack a glyceraldehyde- 1,3-bisphospho- respiratory chain. 3-phosphate glycerate They must reoxidize NADH produced in Glycolysis through some other reaction, because NAD+ is needed for the Glyceraldehyde-3-phosphate Dehydrogenase reaction. Usually NADH is reoxidized as pyruvate is converted to a more reduced compound. The complete pathway, including Glycolysis and the reoxidation of NADH, is called fermentation.  Lactate Dehydrogenase O O− O O− C NADH + H+ NAD+ C C O HC OH CH3 CH3 pyruvate lactate E.g., Lactate Dehydrogenase catalyzes reduction of the keto in pyruvate to a hydroxyl, yielding lactate, as NADH is oxidized to NAD+. Lactate, in addition to being an end-product of fermentation, serves as a mobile form of nutrient energy, & possibly as a signal molecule in mammalian organisms. Cell membranes contain carrier proteins that facilitate transport of lactate.  Lactate Dehydrogenase O O− O O− C NADH + H+ NAD+ C C O HC OH CH3 CH3 pyruvate lactate Skeletal muscles ferment glucose to lactate during exercise, when the exertion is brief and intense. Lactate released to the blood may be taken up by other tissues, or by skeletal muscle after exercise, and converted via Lactate Dehydrogenase back to pyruvate, which may be oxidized in Krebs Cycle or (in liver) converted to back to glucose via gluconeogenesis  Lactate Dehydrogenase O O− O O− C NADH + H+ NAD+ C C O HC OH CH3 CH3 pyruvate lactate Lactate serves as a fuel source for cardiac muscle as well as brain neurons. Astrocytes, which surround and protect neurons in the brain, ferment glucose to lactate and release it. Lactate taken up by adjacent neurons is converted to pyruvate that is oxidized via Krebs Cycle.  Pyruvate Alcohol Decarboxylase Dehydrogenase O O− CO2 H NADH + H+ NAD+ H C O C O C H C OH CH3 CH3 CH3 pyruvate acetaldehyde ethanol Some anaerobic organisms metabolize pyruvate to ethanol, which is excreted as a waste product. NADH is converted to NAD+ in the reaction catalyzed by Alcohol Dehydrogenase. Pyruvate carboxylation, decarboxylation shares in carbohydrate metabolism  Regulation of Glycolysis:- The rate of glycolysis is regulated by the control of the 3 irreversible enzymes (key enzymes), these enzymes are Glucokinase,hexokinase, phosphofructokinase 1 and pyruvate kinase. 1- Hormonal regulation: a- Insulin stimulates the biosynthesis of the last three enzymes, stimulating glycolysis. b- Adrenaline, glugacon inhibit pyruvate kinase, inhibiting glycolysis. 2- Effect of substrates: a- G-6-P inhibits hexokinase (not glucokinase). b- Citrate inhibits phosphfructokinase. 3- Role of energy in regulation: a- High levels of ADP, AMP means low energy concentration in the cells, so stimulate phosphfructokinase. b- High levels of ATP means high energy so it inhibits phosphfructokinase, pyruvate kinase and glycolysis Sources of lactate: Skeletal muscles ferment glucose to lactate during exercise, when the exertion is brief and intense. Astrocytes, which surround and protect neurons in the brain, ferment glucose to lactate and release it. RBCs, since no way to regenerate NAD except by reducing pyruvate into lactate by LDH (no mitochondria in RBCs) -Lactate, in addition to being an end-product of fermentation, serves as a mobile form of nutrient energy. Cell membranes contain carrier proteins that facilitate transport of lactate. -Lactate released to the blood may be taken up by other tissues, or by skeletal muscle after exercise, and converted by LDH back into pyruvate, which may be oxidized in Krebs Cycle or converted back to glucose via gluconeogenesis in the liver.