Learning Objectives
- Identify the rate-limiting step for each major metabolic pathway.
- Predict how allosteric effectors (AMP, ATP, Citrate) shift metabolic flux.
- Understand the hormonal regulation (Insulin vs. Glucagon) of fuel storage and mobilization.
1. Carbohydrate Metabolism
The balance between energy production and storage is tightly controlled by adenine nucleotides and hormonal signals.
| Process | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Glycolysis | PFK-1 | (+) AMP, F-2,6-BP (-) ATP, Citrate |
| Gluconeogenesis | Fructose-1,6-bisphosphatase 1 | (-) AMP, F-2,6-BP |
| TCA Cycle | Isocitrate dehydrogenase | (+) ADP; (-) ATP, NADH |
| Glycogenesis | Glycogen synthase | (+) G6P, Insulin (-) Glucagon, Epinephrine |
| Glycogenolysis | Glycogen phosphorylase | (+) Epinephrine, AMP (-) Insulin, ATP |
Activity
2. Lipid and Nucleotide Metabolism
Metabolism of fats and nucleotides is regulated to ensure precursor availability and prevent futile cycling.
| Process | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Fatty Acid Synthesis | Acetyl-CoA carboxylase (ACC) | (+) Insulin, Citrate (-) Glucagon, Palmitoyl-CoA |
| Fatty Acid Oxidation | Carnitine acyltransferase I | (-) Malonyl-CoA |
| Cholesterol Synthesis | HMG-CoA reductase | (+) Insulin, Thyroxine (-) Glucagon, Cholesterol |
| Urea Cycle | CPS I | (+) N-acetylglutamate |
Activity
Clinical Correlate: Statins
Statins are competitive inhibitors of HMG-CoA reductase. By inhibiting this rate-limiting step, they reduce endogenous cholesterol production and upregulate LDL receptor expression on hepatocytes.
Mnemonic
Ketogenesis: HMG-CoA Synthase… “Hey My God! I’m starving!”