Hexokinase vs Glucokinase Regulation
| Feature | Hexokinase | Glucokinase | Mnemonic |
| Location | Most tissues (muscle, brain) | Liver and pancreatic β-cells | “H in Human Tissues, G in Glucose Factories” |
| Affinity for Glucose (Km) | Low Km (high affinity) | High Km (active only at high glucose) | “Hexokinase is Hungry, Glucokinase is Greedy” |
| Allosteric Inhibition | Inhibited by Glucose-6-Phosphate | No inhibition by Glucose-6-Phosphate | “Hexo Stops Itself, Gluco Keeps Going” |
| Induction / Repression | No significant hormonal regulation | Induced by Insulin, repressed by Glucagon | “Insulin Induces, Glucagon Grounds” |
Regulation of Glycolysis
| Enzyme | Activators | Inhibitors | Regulation Mechanism | Mnemonic |
| Phosphofructokinase-1 (PFK-1) | AMP, Fructose 2,6-bisphosphate | ATP, Citrate | Allosteric Regulation & Induced by Insulin | “AMP and F-2,6BP Fire PFK, ATP and Citrate Cease It” |
| Pyruvate Kinase | Fructose 1,6-bisphosphate | ATP, Alanine | Allosteric & Covalent Modification | “F-1,6-BP Fires Pyruvate Kinase, Alanine Arrests It” |
Regulation of Pyruvate Dehydrogenase Complex (PDH Complex)
| Activator | Inhibitor | Regulation Mechanism | Mnemonic |
| Ca²⁺, ADP, NAD⁺ | ATP, Acetyl-CoA, NADH | Allosteric Regulation & Covalent Modification | “Ca Activates, ATP Stops” |
Regulation of TCA Cycle
| Enzyme | Activators | Inhibitors | Regulation Mechanism | Mnemonic |
| Citrate Synthase | — | ATP, NADH | Allosteric Inhibition | “ATP Neglects Citrate” |
| Isocitrate Dehydrogenase | Ca²⁺, ADP | ATP, NADH | Allosteric Regulation | “Ca Activates, ATP Neglects” |
| α-Ketoglutarate Dehydrogenase | Ca²⁺ | ATP, NADH, Succinyl-CoA | Allosteric Regulation & Feedback Inhibition | ” Ca Activates, ATP Neglects, Succinyl-CoA Slows the Cycle” |
Glycolysis: Role of PFK-2, PFK-1, and Pyruvate Kinase in Regulation
- Step 1:
PFK-2 converts Fructose-6-phosphate to Fructose 2,6-bisphosphate.- Fructose 2,6-bisphosphate is a key activator of PFK-1 (enhances glycolysis).
- PFK-2 activity is stimulated by insulin and inhibited by glucagon, aligning glycolysis with the fed state.
- Step 2:
PFK-1 converts Fructose-6-phosphate to Fructose 1,6-bisphosphate.- Fructose 1,6-bisphosphate is critical as it both progresses glycolysis and activates Pyruvate Kinase (feedforward regulation).
- Step 3:
Fructose 1,6-bisphosphate activates Pyruvate Kinase.- This is a classic example of feedforward regulation, ensuring that once the pathway has reached a committed step, the process continues efficiently to produce pyruvate.
Hormonal Control Overview
- Glycolysis:
- Insulin promotes glycolysis by increasing PFK-1 and pyruvate kinase activity.
- Glucagon inhibits glycolysis in the liver by phosphorylating pyruvate kinase.
- PDH Complex:
- Activated by dephosphorylation in response to insulin and Ca²⁺ during muscle contraction.
- Inhibited by phosphorylation (when ATP, Acetyl-CoA, and NADH are high).
- TCA Cycle:
- Ca²⁺ activates key enzymes (Isocitrate and α-Ketoglutarate Dehydrogenase).
- ATP, NADH, and Succinyl-CoA inhibit the cycle through feedback.
Mnemonic Summary
- Hexokinase vs. Glucokinase:
“Hexo Stops Itself, Gluco Keeps Going” - PFK-1 Regulation:
“AMP and F-2,6BP Fire PFK, ATP and Citrate Cease It” - PDH Complex Regulation:
“Ca Activates, ATP Stops”- Ca²⁺, NAD⁺, ADP activate PDH.
- ATP, Acetyl-CoA, NADH inhibit it.
- TCA Cycle Regulation:
“Succinyl-CoA Slows the Cycle”- Ca²⁺, ADP activate the cycle.
- ATP, NADH, Succinyl-CoA inhibit it.
