Learning Objectives
Integrate the major metabolic pathways of carbohydrates, lipids, and proteins. Identify critical enzymatic intersections where metabolic derangements occur. Connect specific cofactors (B-vitamins) to their respective biochemical steps.
1. Integrated Metabolic Map
Metabolism is a complex network in which substrates such as Glucose-6-Phosphate and Pyruvate serve as central hubs for multiple pathways.
| Pathway | Key Enzymes & Notes |
|---|---|
| Glycolysis / Gluconeogenesis | * Hexokinase/Glucokinase: Glucose trapping. * PFK-1: Rate-limiting step of glycolysis. * Glucose-6-phosphatase: Absent in muscle; deficient in Von Gierke disease. |
| TCA Cycle | * Pyruvate Dehydrogenase: Connects glycolysis to TCA cycle (Requires B1, B2, B3, B5, Lipoic Acid). * Isocitrate Dehydrogenase: Rate-limiting enzyme. |
| HMP Shunt | * G6PD: Rate-limiting; provides NADPH for glutathione reduction. * Transketolase: Requires Thiamine (B1). |
| Urea Cycle | * CPS I: Occurs in mitochondria; requires N-acetylglutamate. * Ornithine Transcarbamylase: Most common urea cycle defect. |
| Sugar Metabolism | * Aldolase B: Deficient in Hereditary Fructose Intolerance. * Galactose-1-P Uridyltransferase: Deficient in classic galactosemia. |
2. Essential Cofactor Requirements
Several enzymes require specific B-vitamin derivatives to function. Deficiencies in these vitamins often present as systemic metabolic failure.
- B1 (Thiamine): Required by Pyruvate Dehydrogenase, α-ketoglutarate dehydrogenase, and Transketolase.
- B7 (Biotin): Required by all Carboxylases (e.g., Pyruvate carboxylase, Acetyl-CoA carboxylase).
- B12 (Cobalamin): Required for Methylmalonyl-CoA mutase (important for odd-chain fatty acid metabolism).
Clinical Correlate: Fructose Intolerance
In Hereditary Fructose Intolerance, a deficiency in Aldolase B leads to the accumulation of Fructose-1-Phosphate. This depletes intracellular phosphate stores, inhibiting both glycogenolysis and gluconeogenesis, resulting in severe hypoglycemia.