BISC 330L Lecture 26 and 27 Glycolysis Regula on and Gluconeogeneis Chapter 16 Which of the following statements about the glycoly c intermediate fructoseG6Gphosphate is correct a In glycolysis fructoseG6Gphosphate is formed from glucoseG6Gphosphate and is split by the aldol reac on into an aldehyde and a ketone b In glycolysis fructoseG6Gphosphate is an aldol so once phosphorylated to fructoseG1 6G bisphosphate cannot be split by the aldol reac on into an aldehyde and a ketone c In glycolysis fructoseG6Gphosphate is converted to glucoseG6Gphosphate and can then be split by the aldol reac on into an aldehyde and a ketone d In glycolysis fructoseG6Gphosphate is an aldol but is not itself split by the aldol reac on un l phosphorylated to fructoseG1 6Gbisphosphate Reac ons conver ng GAP to 32phosphoglycerate Net outcome of these two reac ons GAP an aldehyde is oxidized to a carboxylic acid 32Phosphoglycerate One molecule of NADH is produced One molecule of ATP is produced Per molecule of glucose 2 NADH and 2 ATP are produced Remember we do this twice as we have formed two molecules of GAP from glucose Stage 2 overview GAP enters a bipar te reac on involving its oxida on by NAD and its joining to orthophosphate ATP is generated in the next step The molecule is rearranged ATP is again generated in the nal step Final reac ons genera ng pyruvate 32PG is rearranged by phosphoglycerate mutase to form 22PG Note that this reac on simply involves a swap of phosphoryl and hydroxyl groups on C22 and C23 Final reac ons genera ng pyruvate free energy release during hydrolysis G0 213 kcal J G0 262 kcal J To generate a compound of high phosphoryl2transfer poten al the bond linking C2 and C3 needs to be converted from a single to a double bond crea ng an enol This is accomplished via a dehydra on reac on catalyzed by enolase which results in the release of a water molecule Final reac ons genera ng pyruvate Pyruvate kinase Pyruvate kinase then catalyzes transfer of the phosphoryl group to ADP to form ATP This reac on clari es why phosphoenolpyruvate has high phosphoryl2transfer poten al the phosphoryl group traps the molecule in the unstable enol form As soon as the phosphoryl group is removed the enol form rapidly converts to the more stable keto form ie pyruvate Whew That s glycolysis Next up What happens to Pyruvate A few di erent op ons Which of the following statements about the reac ons of glycolysis is correct a In glycolysis glucoseG6Gphosphate is split into glyceraldehydeG3Gphosphate and dihydroxyacetone phosphate b In glycolysis fructoseG1 6Gbisphosphate is split into glyceraldehydeG3Gphosphate and dihydroxyacetone phosphate c In glycolysis fructoseG6Gphosphate is split into glyceraldehydeG3Gphosphate and dihydroxyacetone phosphate d In glycolysis glucoseG6Gphosphate is isomerized to fructoseG1 6Gbisphosphate Summary the reac ons of glycolysis 2 pyruvate 2 ATP 2 NADH 2 H 2 Net reac on Glucose 2 Pi 2 ADP 2 NAD H2O Total energy released in the conversion of 1 glucose to 2 pyruvates 296kJ mol All of this was anaerobic respira on we will see that much more energy is released from glucose once oxygen gets involved Maintaining redox balance during glycolysis NAD is converted to NADH when GAP is 1 32BPG Cells need to replenish NAD or the pathway will shut down To accomplish this cells metabolize pyruvate in a way that makes more NAD Three di erent fates for pyruvate anaerobic anaerobic aerobic Three di erent fates for pyruvate anaerobic anaerobic aerobic Fermenta on of pyruvate to ethanol yeasts and other microorganisms 22step process 1 Decarboxyla on of pyruvate to yield acetaldehyde 2 Reduc on of acetaldehyde by NADH to yield NAD and ethanol Net reac on for alcoholic fermenta on Glucose 2 Pi 2 ADP 2 ethanol 2 ATP 2 CO2 2 H2O Redox balance during glycolysis Wine2making crush grapes add yeast allow fermenta on strain bo le age drink Why do some people turn red aaer drinking A de ciency in acetaldehyde dehydrogenase causes acetaldehyde buildup and this causes red face Three di erent fates for pyruvate anaerobic anaerobic aerobic Fermenta on of pyruvate to lactate Reac on occurs in microogranisms and in our ssues under condi ons of low oxygen availability e g strenuous exercise lactate build2up makes your muscles sore Net reac on for lac c acid fermenta on Glucose 2 Pi 2 ADP 2 lactate 2 ATP 2 H2O Obligate anaerobes Although energy extrac on by fermenta on is ine cient some organisms have evolved to live in low2 or no oxygen environments and thus they can no longer survive in an oxygenated environment Some of these are nasty and pathogenic Three di erent fates for pyruvate anaerobic anaerobic aerobic Alterna ve entry points into glycolysis Galactose and fructose are good energy sources yet lack dedicated pathways for processing Feeding fructose into glycolysis the fructose 12phosphate pathway Step 1 phosphoryla on of fructose to yield F 12P Step 2 splifng of F 12P into glyceraldehyde and DHAP via aldol cleavage DHAP glycolysis a er isomeriza4on Step 3 phosphoryla on of glyceraldehyde to GAP GAP glycolysis What about galactose Galactose is phosphorylated to form galactose 12phosphate Processing of galactose 12P Galactose 12P receives a uridyl group from UDP2glucose Glucose 12phosphate is released and isomerized to glucose 62 phosphate which can enter glycolysis Note that UDP2galactose is converted back to UDP2glucose by an epimerase Thus no UDP2glucose is used up in this pathway Net reac on Galactose ATP glucose 12phosphate ADP H Why are some people lactose intolerant De ciency in lactase enzyme prevents conversion of lactose to galactose glucose Why this is a problem Lactose build2up allows microorganisms in the colon to ferment it to lac c acid with methane and hydrogen gas as byproducts Result is atulence In addi on the lactate produced by microorganisms draws water into the intes ne causing diarrhea And if that weren t enough severe gas and diarrhea hinder uptake of fats proteins and other nutrients Glycolysis 22 regula on Glycolysis has 2 func ons 1 produce ATP 2 produce building blocks for other biosynthe c reac ons With these dual purposes regula on is important Irreversible reac ons are common points for regulatory interven on see arrows Glycolysis 22 regula on How do di erent ssues balance the need for ATP with other u liza ons of glucose We consider 2 examples muscle liver Regula on of glycolysis in muscle Primary control of muscle glycolysis is the energy charge of the cell Recall that