Glycolysis Flashcards
True commitment step
Primary regulatory site
6-phosphofructo-1-kinase (PFK1)
Fructose 6-phosphate->Fructose 1,6-bisphosphate (ATP->ADP)
Enzyme that traps glucose in the cell
Hexokinase
Hexokinase
Mg2+ is a cofactors, bound to ATP commits glucose to metabolic pathway, traps glucose in cell
Aldolase
Fructose 1,6-biphosphate->dihydroxyacetone phosphate (DHAP) + glyceraldehyde 3-phosphate (GAP)
Convert DHAP ->GAP via triose phosphate isomerase
1st substrate level phosphorylation:
Coupled rxns/enzymes
Common intermediate
Coupled rxns/enzymes:
1) glyceraldehyde 3-phosphate dehydrogenase
2) 3-phosphoglycerate kinase
Intermediate: 1,3 bisphosphoglycerate
Production of 2,3 BPG
Erythrocytes have another mutase that converts 1,3-biphosphoglycerate->2,3 BPG
Biphosphoglycerate mutase
2nd substrate level phosphorylation
Coupled rxns/enzymes
Common intermediate
Coupled rxns/enzymes
1) Enolase
2) Pyruvate Kinase
Intermediate: phosphoenolpyruvate (PEP)
Why is ATP production decreased in PK deficiency?
PK catalyzes one of the ATP-producing rxns of glycolysis (2nd substrate level phosphorylation)
Why might ATP synthesis from glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase be inhibited by PK deficiency?
No PK->Pyruvate can’t be produced->no way in the RBC to re-ox NADH generated in the glyceraldehyde-3-phosphate dehydrogenase rxn because they lack mitochondria, thus can’t generate 1,3-biphosphoglycerate
Why are RBC especially vulnerable to the reduction in ATP from glycolysis?
RBC lack mitochondria->Pyruvate is reduced to lactate (anaerobic glycolysis) which enters plasma
RBC unable to completely oxidized glucose to CO2+H2O, and so are dependent on glycolysis for ATP production
In PK deficiency, levels of 2,3-BPG may increase three-fold. Why?
Build up in substrate makes minor pathways into major ones PK->buildup of PEP Reversible rxns going backwards: Enolase Phosphoglycerate mutase 3-
10 enzymes of aerobic glycolysis
Hexokinase Phosphoglucose isomerase PFK-1 Aldolase Triose phosphate isomerase Glyceraldehyde 3-phosphate dehydrogenase 3-phosphoglycerate kinase Phosphoglycerate mutase Enolase Pyruvate kinase*
Enzyme special to anaerobic tissue glycolysis.
What does it do?
Lactate dehydrogenase
Reduces: Pyruvate->lactate
Oxidizes: NADH->NAD
Anaerobic tissues lack mitochondria, thus need different way of re-oxidizing NADH to continue the cycle
Pyruvate Kinase Deficiency
Not really a deficiency->mutation
Increased Km=lower affinity for its substrate PEP
Premature hemolysis of RBC’s: hemolytic anemia
Amish-auto recessive
Most common enzymopathy of glycolysis
Enzymes that catalyze irreversible reactions
Hexokinase
PFK-1/6 phosphofructo-1-kinase
Pyruvate kinase
PFK-1
3rd step
2nd irreversible, true commitment step of glycolysis, primary regulatory site
Fructose 6 phosphate-> fructose 1,6-bisphosphate uses one ATP
Dehydroxyacetone Phosphate
DHAP
Produced w/GAP from fructose 1,6-bisphosphate by aldolase
Not used in glycolysis
Need triose phosphate isomerase to convert DHAP->GAP
Pyruvate Kinase
Last irreversible rxn of aerobic glycolysis
PEP->Pyruvate+ATP
Substrate and Products for aldolase
Substrate:fructose 1,6-bisphosphate
Products : DHAP(ketose) & GAP(aldose)
Oxidation of 1 mol glucose to lactate generates a net of _ ATP
2 ATP
Substrate level phosphorylation
SLP
synthesis of ATP via 2 coupled reactions involves a high-energy common intermediate
Enzyme that generates NADH
Glyceraldehyde 3 phosphate dehydrogenase
(1st SLP)
GAP-> 1,3 bisphosphoglycerate
What happens to NADH in aerobic conditions?
NADH is oxidized by a substrate such as oxaloacetate, whose reduced form (malate) can be transported across a mitochondrial membrane
In glycolysis one mole of orthophosphate (Pi) is consumed in a reaction catalyzed by what enzyme?
Glyceraldehyde 3-phosphate
Reduces NAD to NADH
First enzyme in first SLP
GAP -> 1,3 bisphosphoglycerate
Enzyme that uses ATP
1) Hexokinase
Cosubstrate ATP, Mg2+ is a cofactor bound to ATP
Irreversible, traps glucose as glucose 6-phosphate
2) PFK-1
Irreversible, true commitment step, primary regulatory step
Fructose 6 phosphate + ATP -> fructose 1,6 bisphosphate + ADP
