Principles of Biochemistry Fourth Edition Donald Voet Judith G. Voet harlotte W. Pratt hapter 15 Glycolysis and The Pentose Phosphate Pathway Page No. 47-490
Introduction Glucose: is major source of metabolic energy in many cells. Glycolysis: is Greek: Glykus, sweet + Lysis, loosening). A sequence of 10 enzymatic reactions in which one of glucose is converted to two molecules of pyruvate, with the concomitant generation of ATP
verview of Glycolysis
1- verview of Glycolysis: Key oncepts 1 Glycolysis involves the breakdown of glucose to pyruvate while using the free energy released in the process to synthesize ATP from ADP and P i. The 10 reaction sequence of glycolysis is divided into two stages: energy investment and energy recovery.
1- verview of Glycolysis The enzymes of glycolysis are located in cytosol. Glycolysis convert glucose to two 3 units (Pyruvate). The free energy released in the process is harvest to synthesis ATP from ADP and Pi. Thus, glycolysis is a pathway of chemically coupled phosphorylation reactions. Glycolysis can be divided into two stages: 1 - Stage I Energy Investment. - Stage II Energy Recovery.
1- Stage I Energy Investment (reactions 1 5): In this preparatory stage, the hexose glucose is phosphorylated and cleaved to yield molecules of the triose glyceraldehyde 3 - phosphate (G 3 P). This process consumes ATP. - Stage II Energy Recovery (reactions 6 10): Two molecules of glyceraldehyde 3 phosphate are converted to pyruvate, with concomitant generation of 4 ATP. Glycolysis therefore has a net profit of ATP per glucose Stage I consumes ATP; Stage II produces 4 ATP
Stage-I
Glycolysis continued. Stage-II Recall that there are GAP per glucose.
1- verview of Glycolysis Figure 15-1: Glycolysis in the first stage (reactions 1 5) one molecule of glucose is converted to two glyceraldehyde 3 phosphate (GAP) molecules in a series of reactions of that consumes ATP.
1- verview of Glycolysis Figure 15-1: Glycolysis in the seconded stage of glycolysis (reactions 6 10) the two glyceraldehyde 3 phosphate molecules converted to two pyruvate molecules, generating 4 ATP and NAD.
1- verview of Glycolysis Figure 15-1: Glycolysis in the seconded stage of glycolysis (reactions 6 10) the two glyceraldehyde 3 phosphate molecules converted to two pyruvate molecules, generating 4 ATP and NAD.
A- exokinase Uses the First ATP Reaction 1 of glycolysis is the transfer of phosphoryl group from ATP to glucose to form glucose 6 phosphate (G6P) in a reaction catalyzed by hexokinase. 4 6 5 3 glucose 6 P 3 ATP ADP 5 4 1 1 Mg + exokinase 3 glucose-6-phosphate Reaction 1 of glycolysis.
A- exokinase Uses the First ATP A kinase: is An enzyme that transfers phosphoryl groups between ATP and a metabolite. A ubiquitous, relatively nonspecific enzyme that catalyzes the phosphorylation of hexoses such as D Glucose, D Mannose, and D Fructose. Liver cells also contain the isozyme Glucokinase, which catalyzes the same reaction but which is involved in maintaining blood glucose levels. primarily
B Phosphoglucose Isomerase onverts Glucose 6 Phosphate to Fructose 6 - Phosphate Reaction of glycolysis is the conversion of G6P to Fructose 6 - Phosphate (F6P) by phosphoglucose isomerase (PGI). This is the isomerization of an aldose to ketose. 4 6 5 P 3 3 1 5 P 3 Reaction of glycolysis. 6 4 3 1 Phosphoglucose Isomerase glucose-6-phosphate fructose-6-phosphate
B Phosphoglucose Isomerase onverts G6P to F6P Since G6P and F6P both exist predominantly in their forms, the reaction requires ring opening followed by isomerizations and subsequent ring closure (the interconversions of cyclic and linear forms of hexoses are shown in Fig. 8 3).
Phosphofructokinase Uses The Second ATP In Reaction 3 of glycolysis, Phosphofructokinase (PFK) phosphorylates F6P to yield Fructose 1, 6 bisphosphate (FBP or F1,6P). Phosphofructokinase 6 P 3 5 1 6 P 3 ATP ADP 5 1 P 3 4 3 fructose-6-phosphate Mg + 4 3 fructose-1,6-bisphosphate Reaction 3 of glycolysis. The product is a bisphosphate rather than a diphosphate because its two phosphate groups
Phosphofructokinase Uses The Second ATP Phosphofructokinase (PFK) The PFK reaction is similar to the hexokinase reaction. It plays a central role in control of glycolysis because it catalyzes one of the pathway, s Rate-determining Reactions. In many organisms, the activity of PFK is enhanced allosterically by several substances, including AMP, and inhibited allosterically by several other substances, including ATP and citrate.
D Aldolase onverts a 6 - arbon ompound to Two 3 - arbon 1 P 3 3 4 5 6 P 3 3 1 ompounds Aldolase catalyze Reaction 4 of glycolysis, the cleavage of FBP to form the two triose, glyceraldehyde-3- phosphate (GAP) and dihydroxyacetone phosphate (DAP) fructose-1,6- bisphosphate Aldolase P 3 + dihydroxyacetone phosphate 1 3 P 3 glyceraldehyde-3- phosphate Triosephosphate Isomerase
E Triose Phosphate Isomerase (TIM) Interconverts Dihydroxyacetone Phosphate (DAP) and Glyceraldehyde 3 Phosphate (GAP) Reaction 5 of glycolysis 1 P 3 3 4 5 6 P 3 fructose-1,6- bisphosphate Aldolase 3 1 P 3 + 1 3 P 3 dihydroxyacetone glyceraldehyde-3- phosphate phosphate Triosephosphate Isomerase Triose Phosphate Isomerase (TIM) catalyzes: dihydroxyacetone-p glyceraldehyde-3-p Glycolysis continues from glyceraldehyde-3-p
Summary of Stage-1 Figure 15-4: Schematic diagram of the first stage of glycolysis. In this series five reactions, a hexose is phosphorylated, isomerized, phosphorylated again, and then cleaved to two interconvertible triose phosphates. Two ATP are consumed in the process.
F Glyceraldehyde 3 -Phosphate Dehydrogenase Forms The First igh Energy Intermediate. Reaction 6 of glycolysis, is oxidation and phosphorylation of G-3-P by NAD + and P i as catalyzed by Glyceraldehyde- 3-phosphate Dehydrogenase (GAPD) 1 3 P 3 glyceraldehyde- 3-phosphate Glyceraldehyde-3-phosphate Dehydrogenase + P i + + NAD + NAD 1 3 P 3 P 3 1,3-bisphosphoglycerate This is the only step in Glycolysis in which NAD + is reduced to NAD Reaction 6 of glycolysis.
G Phosphoglycerate Kinase Generates The First ATP. Reaction together reaction (PGK). 7 of glycolysis pathway yields ATP with 3 phosphoglycerate (3 PG) in catalyzed by Phosphoglycerate Kinase 1 Phosphoglycerate Kinase P 3 ADP ATP Reaction 7 of glycolysis. Mg + 3 P 3 3 1,3-bisphosphoglycerate 1 P 3 3-phosphoglycerate
Phosphoroglycerate Mutase Interconverts 3 Phosphoroglycerate and Phosphoglycerate. 1 3 Phosphoglycerate Mutase P 3 3-phosphoglycerate 1 3 P 3 -phosphoglycerate A mutase catalyzes the transfer of functional group from one position to another on a molecule. Phosphate is shifted from the on 3 to the on. Reaction 8 of glycolysis.
I Enolase Forms The Second igh Energy Intermediate. In Reaction 9 of glycolysis, PG is dehydrated to Phosphoenolpyruvate (PEP) in a reaction catalyzed by Enolase. Enolase 1 3 P 3 P 3 1 3 P 3 -phosphoglycerate enolate intermediate phosphoenolpyruvate Reaction 9 of glycolysis.
J Pyruvate Kinase Generates The Second ATP. In Reaction 10 of glycolysis, its final reaction, Pyruvate Kinase (PK) couples the free energy of PEP cleavage to the synthesis of ATP during the formation of pyruvate. 1 P 3 Pyruvate Kinase ADP ATP 1 3 phosphoenolpyruvate 3 3 pyruvate Reaction 10 of glycolysis.
Summary of Stage II Figure 15-15: Schematic diagram of the second stage of glycolysis. In this series five reactions, GAP undergoes phosphorylation, and oxidation, followed by molecular rearrangement, so that both phosphoryl groups have sufficient free energy to be transferred ADP to product ATP, two molecules of GAP are converted to pyruvate for every molecule of glucose that enter stage I of glycolysis.
onclusion ATP: ATP consumed per glucose in stage I. 4 ATP generated in stage II (two for each GAP). ATP a net yield per glucose. Satisfies most of the cell's energy needs, NAD: Glucose is oxidized to the extent that two NAD + are reduced to two NAD (reduced coenzyme). Represent a source of free energy which can be recovered by their subsequent oxidation.
Pyruvate: The two pyruvate molecules produced through oxidation of per glucose molecules verall reaction of Glycolysis Glucose + NAD + + ADP + P i pyruvate + NAD + ATP + 4+
Quick Revision of Glycolysis
Net generation of ATPs, NAD and pyruvates during glycolysis
What Next? Figure 15-16: Metabolic Fate of Pyruvate.