Which heavy metal binds to sulfhydryl groups of enzymes and causes inhibition of cellular respiration, making it the most acutely toxic?

Explanation

## Arsenic: Mechanism of Acute Toxicity **Key Point:** Arsenic (specifically arsenite, As³⁺) binds irreversibly to sulfhydryl (–SH) groups of critical enzymes, particularly pyruvate dehydrogenase and other oxidative enzymes, causing rapid inhibition of cellular respiration and acute toxicity. ### Mechanism of Arsenic Toxicity ```mermaid flowchart TD A[Arsenic exposure]:::outcome --> B[Arsenite As³⁺ enters cells]:::action B --> C[Binds to SH groups of enzymes]:::action C --> D{Which enzymes affected?}:::decision D -->|Pyruvate dehydrogenase| E[Inhibition of TCA cycle]:::urgent D -->|Cytochrome oxidase| F[Inhibition of electron transport]:::urgent D -->|Other SH-containing enzymes| G[Cellular respiration blocked]:::urgent E --> H[Acute cellular hypoxia]:::urgent F --> H G --> H H --> I[Shock, multi-organ failure]:::urgent ``` ### Why Arsenic Is Most Acutely Toxic | Heavy Metal | Binding Target | Acute Effect | Mechanism | |-------------|----------------|--------------|----------| | **Arsenic** | SH groups (–SH) | Immediate enzyme inhibition | Blocks TCA cycle & electron transport | | **Mercury** | SH groups | Slower onset | Protein denaturation over time | | **Lead** | Calcium channels, ALA dehydratase | Subacute/chronic | Interferes with heme synthesis | | **Cadmium** | Metallothionein binding | Chronic accumulation | Renal & bone toxicity | **High-Yield:** Arsenic's acute toxicity is due to the **irreversible** binding to pyruvate dehydrogenase (PDH), which is essential for the TCA cycle. This causes immediate cellular energy depletion and shock. **Mnemonic:** **ASHES** — Arsenic binds Sulfhydryl groups, causing Hypoxia, Energy depletion, and Shock. **Clinical Pearl:** Acute arsenic poisoning presents with severe gastroenteritis, cardiovascular collapse, and shock within hours—far more rapidly than chronic heavy metal poisonings. This acute presentation reflects the immediate blockade of cellular respiration. [cite:Parikh's Textbook of Medical Jurisprudence Ch 24; Robbins 10e Ch 9]