P5C

Pyrroline-5-carboxylate, commonly abbreviated P5C, is a key intermediate in cellular proline metabolism. It is a five-membered ring structure that can exist in equilibrium with glutamate semialdehyde, the open-chain form. P5C is produced during the oxidation of proline by proline dehydrogenase and can be further oxidized by P5C dehydrogenase to glutamate, linking proline degradation to the central carbon metabolism. P5C also appears as an intermediate in proline biosynthesis, formed from glutamate semialdehyde and subsequently reduced to proline by P5C reductase.

In metabolic paths, P5C serves as a bridge between proline and glutamate, connecting proline catabolism to the TCA cycle and cellular redox balance through NAD+/NADH couples. The enzyme system that handles its interconversion includes proline dehydrogenase and P5C dehydrogenase for catabolism, and the biosynthetic enzymes glutamate-5-semialdehyde dehydrogenase (often functioning in concert with P5CS and P5CR) for proline production. In plants and other organisms, the proline cycle and P5C flux are linked to responses to osmotic and oxidative stress and to redox regulation.

Genetic and clinical aspects include associations with the enzymes PRODH and ALDH4A1, which encodes P5C dehydrogenase. Defects in these enzymes can lead to hyperprolinemia types I and II, respectively, due to abnormal accumulation of proline or P5C. Such metabolic disturbances are studied for their implications in neurodevelopment and metabolic disorders. P5C thus has significance in physiology, cellular stress responses, and human disease, while also serving as a well-characterized model substrate in biochemical studies of proline metabolism.