Which of the following amino acids is a precursor for the synthesis of glutathione, the major intracellular antioxidant?

Explanation

## Glutathione Synthesis and Cysteine **Key Point:** Cysteine is the critical sulphur-containing amino acid required for glutathione (GSH) synthesis, the tripeptide γ-glutamyl-cysteinyl-glycine. ### Glutathione Structure and Function Glutathione is a tripeptide composed of: 1. Glutamic acid (γ-carboxyl group linkage) 2. **Cysteine** (provides the reactive thiol group -SH) 3. Glycine The cysteine residue provides the reactive sulphydryl group that acts as the antioxidant centre, capable of reducing oxidative stress and free radicals. ### Synthesis Pathway ```mermaid flowchart LR A[Glutamic acid + Cysteine]:::action --> B[γ-glutamylcysteine synthetase]:::action B --> C[γ-glutamylcysteine]:::outcome C --> D[Glutathione synthetase]:::action D --> E[Glutathione GSH]:::outcome E --> F[Antioxidant defence]:::action ``` ### Role of Cysteine - Cysteine is derived from methionine via the transsulphuration pathway - The thiol (-SH) group of cysteine is essential for the reducing capacity of glutathione - Deficiency of cysteine impairs glutathione synthesis and antioxidant capacity **High-Yield:** Glutathione exists in two forms: - **Reduced (GSH):** active antioxidant form - **Oxidized (GSSG):** after reduction of free radicals; recycled by glutathione reductase (NADPH-dependent) **Clinical Pearl:** Glutathione depletion occurs in conditions of oxidative stress (sepsis, HIV/AIDS, chemotherapy) and is associated with increased cellular damage.