Regulation of Glycolysis

Glycolysis is a tightly regulated pathway. Only the irreversible enzymes (hexokinase,
phosphofructokinase, pyruvate kinase) can be regulated. Phosphofructokinase is by far the most regulated
enzyme. Regulation can occur in several ways:
1. allosteric modulators
2. hormone control (through phosphorylation/dephosphorylation)
3. de novo synthesis
Inhibitor and Toxins
1. Arsenate – affects GAP dehydrogenase
Arsenate looks like Pi and is added to GAP by GAP dehydrogenase instead of Pi. The arsenate group is
removed by phosphoglycerate kinase in step 7, but no ATP is generated in this step. Therefore, get 0 net
ATP from glycolysis. Glycolysis is not halted, but no ATP is produced. This is detrimental to RBC.
2. Iodoacetate (iodoacetamide) – inhibits GAP dehydrogenase
Inhibits GAP dehydrogenase by irreversibly binding to the Cys residue in the active site rendering the
enzyme inactive.
3. Fluoride ion – inhibits enolase
Fluoride ion complexes with the Mg+2 ion at the active site of the enzyme rendering the enzyme inactive.