1-pyrroline-5-carboxylate dehydrogenase

1-Pyrroline-5-carboxylate dehydrogenase (P5CDH) is an enzyme that plays a crucial role in the proline degradation pathway. It catalyzes the conversion of 1-pyrroline-5-carboxylate (P5C) to glutamate, an important amino acid in the human body. This reaction is a part of the urea cycle and is essential for the proper metabolism of proline.

Function

1-Pyrroline-5-carboxylate dehydrogenase is involved in the second step of proline degradation. The enzyme oxidizes P5C to glutamate, using NAD+ as a cofactor, which is reduced to NADH in the process. This reaction is important for maintaining the balance of amino acids and for the production of energy in the form of ATP.

Structure

P5CDH is a mitochondrial enzyme, meaning it is located within the mitochondria of cells. It is encoded by the ALDH4A1 gene in humans. The enzyme belongs to the aldehyde dehydrogenase family, which is characterized by its ability to oxidize aldehydes to carboxylic acids.

Clinical Significance

Deficiency in 1-pyrroline-5-carboxylate dehydrogenase activity can lead to a rare metabolic disorder known as Hyperprolinemia type II. This condition is characterized by elevated levels of proline and P5C in the blood, which can result in neurological problems and other symptoms. Genetic mutations in the ALDH4A1 gene are responsible for this deficiency.

Pathway

The proline degradation pathway involves several steps:

1. Proline is first converted to 1-pyrroline-5-carboxylate by the enzyme proline dehydrogenase. 2. 1-Pyrroline-5-carboxylate is then oxidized to glutamate by 1-pyrroline-5-carboxylate dehydrogenase. 3. Glutamate can enter the citric acid cycle or be used in the synthesis of other amino acids.

Also see

• Proline metabolism
• Amino acid metabolism
• Aldehyde dehydrogenase
• Hyperprolinemia