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