120 PANEL 2–8: Details of the 10 Steps of Glycolysis <GGGC> For each step, the part of the molecule that undergoes a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box. CH2OH STEP 1 Glucose is phosphorylated by ATP to form a sugar phosphate. The negative charge of the phosphate prevents passage of the sugar phosphate through the plasma membrane, trapping glucose inside the cell. CH2O P O + OH HO O hexokinase ATP OH + OH HO OH glucose 6-phosphate H O 1CH2OH C1 H C 2 OH HO C H H C OH 3 4 H C 5 phosphoglucose isomerase O C 2 HO H OH H CH2O P 6 C H C OH 3 4 C 2 3 OH 4 OH (ring form) + P OH2C CH2O P HO OH OH CH2O P O ATP + HO + fructose 1,6-bisphosphate HO C O C H H C OH H C OH CH2O P aldolase HO C O C H H (open chain form) fructose 1,6-bisphosphate dihydroxyacetone phosphate + C OH CH2O P dihydroxyacetone phosphate O H CH2O P C H triose phosphate isomerase O O H C H C OH CH2O P glyceraldehyde 3-phosphate glyceraldehyde 3-phosphate + H OH CH2O P CH2OH ADP OH CH2O P C HO (open chain form) phosphofructokinase (ring form) STEP 5 The other product of step 4, dihydroxyacetone phosphate, is isomerized to form glyceraldehyde 3-phosphate. 5 1 fructose 6-phosphate STEP 3 The new hydroxyl P OH2C CH2OH O group on carbon 1 is phosphorylated by ATP, in HO preparation for the formation of two three-carbon sugar OH phosphates. The entry of sugars OH into glycolysis is controlled at this step, through regulation of the fructose 6-phosphate enzyme phosphofructokinase. O CH2OH O 6 CH2O P 6 (open chain form) P OH2C P OH2C OH 5 glucose 6-phosphate STEP 4 The six-carbon sugar is cleaved to produce two three-carbon molecules. Only the glyceraldehyde 3-phosphate can proceed immediately through glycolysis. H+ OH OH glucose STEP 2 A readily reversible rearrangement of the chemical 6 CH2O P structure 5 O (isomerization) moves the 4 1 carbonyl oxygen OH from carbon 1 to HO 2 OH 3 carbon 2, forming a ketose from an OH aldose sugar. (See Panel 2–4.) (ring form) + ADP CHAPTER 2 PANELS 121 STEP 6 H O The two molecules of glyceraldehyde 3-phosphate C are oxidized. The energy generation phase of glycolysis H C OH + begins, as NADH and a new high-energy anhydride linkage CH2O P to phosphate are formed (see Figure 2–73). glyceraldehyde 3-phosphate + NAD+ C H P 1,3-bisphosphoglycerate + C ADP H + C ATP OH CH2O P CH2O P 1,3-bisphosphoglycerate 3-phosphoglycerate O– O C H C 2 C phosphoglycerate mutase OH H C CH2O P 2-phosphoglycerate O– O C C enolase O P C CH2OH C pyruvate kinase O P H2O + ATP O– O + + phosphoenolpyruvate O– C O P CH2 2-phosphoglycerate O O– O C H O P CH2OH 3 3-phosphoglycerate STEP 9 The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage. O– O 1 STEP 10 The transfer to ADP of the high-energy phosphate group that was generated in step 9 forms ATP, completing glycolysis. O– O OH STEP 8 The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate. ADP + C + H C O CH2 CH3 phosphoenolpyruvate pyruvate NET RESULT OF GLYCOLYSIS O– O C CH2OH O HO C NADH OH ATP O– O OH O CH3 ATP OH C ATP ATP NADH ATP ATP C O CH3 glucose H+ OH phosphoglycerate kinase C + NADH CH2O P C H + C O P O STEP 7 The transfer to ADP of the high-energy phosphate group that was generated in step 6 forms ATP. O P O glyceraldehyde 3-phosphate dehydrogenase In addition to the pyruvate, the net products are two molecules of ATP and two molecules of NADH two molecules of pyruvate