glutathione biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins. [GOC:ai, GOC:al, GOC:pde, ISBN:0198506732]

Glutathione biosynthesis is a fundamental metabolic process that generates the tripeptide glutathione (GSH), a ubiquitous and essential molecule with diverse roles in cellular homeostasis and detoxification. The synthesis of GSH occurs in two steps, catalyzed by two distinct enzymes:

1. **γ-Glutamylcysteine synthetase (γ-GCS):** This enzyme catalyzes the ATP-dependent condensation of glutamate and cysteine, forming γ-glutamylcysteine. This step is the rate-limiting step in glutathione synthesis and is subject to tight regulation.

2. **Glutathione synthetase:** This enzyme adds glycine to γ-glutamylcysteine, forming glutathione (GSH).

**Detailed description of the process:**

* **Step 1: Formation of γ-Glutamylcysteine:**
* The reaction is initiated by the binding of glutamate and ATP to γ-GCS.
* ATP is hydrolyzed to ADP and inorganic phosphate (Pi), providing the energy for the reaction.
* The activated glutamate molecule reacts with cysteine, forming γ-glutamylcysteine.
* γ-GCS is highly regulated, with its activity being influenced by factors such as substrate availability, oxidative stress, and cellular redox state.

* **Step 2: Addition of Glycine:**
* γ-Glutamylcysteine binds to glutathione synthetase.
* Glycine is then added to the γ-glutamylcysteine molecule, forming glutathione.
* This step requires the hydrolysis of ATP to ADP and Pi, similar to the first step.

**Overall, glutathione biosynthesis is a tightly regulated process that ensures the adequate supply of GSH for its various cellular functions, including:**

* **Antioxidant defense:** GSH acts as a primary antioxidant, scavenging reactive oxygen species (ROS) and protecting cells from oxidative damage.
* **Detoxification:** GSH conjugates with various toxic substances, facilitating their excretion from the cell.
* **Enzyme activity:** GSH is a cofactor for numerous enzymes involved in various cellular processes, including DNA synthesis and repair.
* **Immune response:** GSH supports immune cell function and promotes inflammation resolution.

**Disruptions in glutathione biosynthesis can lead to various health problems, highlighting its importance in maintaining cellular homeostasis and overall health.**'
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Proteins (3)

Compounds (16)