Which heavy metal binds to sulfhydryl groups of cellular enzymes and causes inhibition of oxidative metabolism?

Explanation

## Arsenic: Mechanism of Cellular Toxicity **Key Point:** Arsenic (As³⁺) binds covalently to sulfhydryl (–SH) groups of critical cellular enzymes, particularly those involved in oxidative metabolism, leading to enzyme inhibition and cellular energy depletion. ### Molecular Mechanism **High-Yield:** Arsenic toxicity operates via the following pathway: 1. **Sulfhydryl binding** — Arsenite (As³⁺) forms stable complexes with –SH groups on cysteine residues in proteins 2. **Target enzymes** — Particularly affects pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and other TCA cycle enzymes 3. **Energy failure** — Inhibition of oxidative metabolism → ATP depletion → cellular dysfunction and death 4. **Reactive oxygen species** — Arsenic also generates ROS, causing oxidative stress ### Comparison of Heavy Metal Mechanisms | Heavy Metal | Primary Mechanism | Target | Clinical Consequence | |-------------|-------------------|--------|----------------------| | **Arsenic** | Sulfhydryl binding | Oxidative enzymes (TCA cycle) | Energy depletion, multi-organ failure | | Lead | Inhibits ALA dehydratase, replaces Ca²⁺ | Heme synthesis, neural/renal function | Anemia, encephalopathy, nephropathy | | Mercury | Sulfhydryl binding (but different enzymes) | Renal tubular cells, CNS | Nephrotic syndrome, tremor, psychosis | | Cadmium | Metallothionein binding, oxidative stress | Renal tubules, bone | Proteinuria, osteomalacia | **Clinical Pearl:** The reason arsenic poisoning causes acute gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) is rapid inhibition of intestinal epithelial cell metabolism, leading to mucosal necrosis and hemorrhage. **Mnemonic:** **ASHES** — Arsenic's toxic effects: - **A**cetyl-CoA dehydrogenase inhibited - **S**ulfhydryl groups targeted - **H**igh mortality in acute poisoning - **E**nergy (ATP) depletion - **S**evere GI and cardiovascular collapse **Warning:** While mercury also binds sulfhydryl groups, it does so with different affinity and targets different enzymes (renal tubular proteins, CNS proteins). Arsenic's primary toxicity is via inhibition of oxidative metabolism enzymes. [cite:Robbins 10e Ch 9]