Heme Synthesis: Key Steps and Regulation
The pathway begins in the mitochondria, moves to the cytosol, and returns to the mitochondria to complete the process.
| Step | Enzyme | Notes |
|---|---|---|
| Initial | ALA Synthase (ALAS) | Rate-limiting step; requires Vitamin B6 (pyridoxine). |
| Second | ALA Dehydratase | Sensitive to lead poisoning. |
| Intermediate | Porphobilinogen Deaminase | Deficiency leads to Acute Intermittent Porphyria. |
| Final | Ferrochelatase | Inserts iron into protoporphyrin IX; also sensitive to lead. |
High-Yield Core Realities:
- Regulation: Heme inhibits ALAS (negative feedback). Glucose and heme also inhibit ALAS expression.
- Lead Poisoning: Inhibits both ALA dehydratase and Ferrochelatase, leading to increased ALA and protoporphyrin levels.
- Porphyrias: Genetic defects in pathway enzymes. Remember the distinction between those causing neurovisceral symptoms (e.g., Acute Intermittent Porphyria) and those causing photosensitivity (e.g., Porphyria Cutanea Tarda).