pyrroline-5-carboxylate reductase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: L-proline + NADP+ = 1-pyrroline-5-carboxylate + NADPH + H+. [EC:1.5.1.2]

Pyrroline-5-carboxylate reductase (P5CR) activity is a critical enzymatic step in the biosynthesis of proline, an essential amino acid. This activity is catalyzed by enzymes belonging to the short-chain dehydrogenase/reductase (SDR) family. The reaction involves the NADPH-dependent reduction of Δ1-pyrroline-5-carboxylate (P5C) to L-proline. P5C is a highly reactive molecule, and its conversion to proline is essential for maintaining cellular redox balance and preventing the accumulation of reactive oxygen species.

P5CR activity plays a key role in various cellular processes, including:

* **Proline biosynthesis:** P5C is a precursor to proline, an essential amino acid involved in protein synthesis, collagen formation, and cellular osmotic regulation.
* **Redox homeostasis:** P5CR activity contributes to redox homeostasis by consuming NADPH and reducing P5C, a reactive molecule that can contribute to oxidative stress.
* **Stress response:** P5CR activity is upregulated under conditions of stress, such as oxidative stress and hypoxia, to support proline synthesis and protect cells from damage.
* **Cell signaling:** Proline is a signaling molecule involved in various cellular processes, including growth, differentiation, and apoptosis.

Mutations in P5CR genes can lead to proline deficiency and various human diseases, including hyperprolinemia type II and certain types of cancer.

The enzymatic mechanism of P5CR involves the following steps:

1. **Binding of NADPH and P5C:** The enzyme binds both NADPH and P5C in its active site.
2. **Hydride transfer:** NADPH donates a hydride ion to P5C, reducing the double bond between carbon 5 and nitrogen 1.
3. **Protonation:** A proton is added to the nitrogen atom, resulting in the formation of L-proline.
4. **Release of proline and NADP+:** L-proline and NADP+ are released from the enzyme.

P5CR activity is tightly regulated in cells to ensure optimal proline levels and maintain cellular homeostasis. The regulation of P5CR activity is complex and involves multiple factors, including substrate availability, enzyme expression, and post-translational modifications.'
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Proteins (1)

Compounds (1)