Inborn errors of proline metabolism.

Publisher: Elsevier Country of Publication: United States NLM ID: 0404243 Publication Model: Print Cited Medium: Internet ISSN: 1541-6100 (Electronic) Linking ISSN: 00223166 NLM ISO Abbreviation: J Nutr Subsets: MEDLINE

Publication: 2023- : [New York, NY] : Elsevier
Original Publication: 1928-1933 : Springfield, Ill. : C. C. Thomas

Amino Acid Metabolism, Inborn Errors/*genetics ; Amino Acid Metabolism, Inborn Errors/*metabolism ; Proline/*metabolism; 1-Pyrroline-5-Carboxylate Dehydrogenase/deficiency ; 1-Pyrroline-5-Carboxylate Dehydrogenase/genetics ; 1-Pyrroline-5-Carboxylate Dehydrogenase/metabolism ; Chromosome Mapping ; Citric Acid Cycle ; Dipeptidases/deficiency ; Dipeptidases/genetics ; Dipeptidases/metabolism ; Gene Deletion ; Humans ; Mental Disorders/genetics ; Nervous System Diseases/genetics ; Proline Oxidase/deficiency ; Proline Oxidase/genetics ; Proline Oxidase/metabolism ; Pyrroline Carboxylate Reductases/deficiency ; Pyrroline Carboxylate Reductases/genetics ; Pyrroline Carboxylate Reductases/metabolism ; delta-1-Pyrroline-5-Carboxylate Reductase

l-Proline concentration is primarily related to the balance of enzymatic activities of proline dehydrogenase [proline oxidase (POX)] and Delta-1-pyrroline-5-carboxylate (P5C) reductase. As a result, P5C plays a pivotal role in maintaining the concentration of proline in body fluids and inborn errors of P5C metabolism lead to disturbance of proline metabolism. Several inborn errors of proline metabolism have been described. Hyperprolinemia type I (HPI) is a result of a deficiency in POX. The POX gene (PRODH) is located on chromosome 22 (22q11.2) and this region is deleted in velo-cardio-facial syndrome, a congenital malformation syndrome. In addition, this gene locus is related to susceptibility to schizophrenia. The other type of hyperprolinemia is HPII. It is caused by a deficiency in P5C dehydrogenase activity. Hypoprolinemia, on the other hand, is found in the recently described deficiency of P5C synthetase. This enzyme defect leads to hyperammonemia associated with hypoornithinemia, hypocitrullinemia, and hypoargininemia other than hypoprolinemia. Hyperhydroxyprolinemia is an autosomal recessive inheritance disorder caused by the deficiency of hydroxyproline oxidase. There are no symptoms and it is believed to be a benign metabolic disorder. The deficiency of ornithine aminotransferase causes transient hyperammonemia during early infancy due to deficiency of ornithine in the urea cycle. In later life, gyrate atrophy of the retina occurs due to hyperornithinemia, a paradoxical phenomenon. Finally, prolidase deficiency is a rare autosomal recessive hereditary disease. Prolidase catalyzes hydrolysis of dipeptide or oligopeptide with a C-terminal proline or hydroxyproline and its deficiency can cause mental retardation and severe skin ulcers.

9DLQ4CIU6V (Proline)
EC 1.2.1.88 (1-Pyrroline-5-Carboxylate Dehydrogenase)
EC 1.2.1.88 (ALDH4A1 protein, human)
EC 1.5.1.- (Pyrroline Carboxylate Reductases)
EC 1.5.3.- (Proline Oxidase)
EC 3.4.13.- (Dipeptidases)
EC 3.4.13.9 (proline dipeptidase)

Date Created: 20080923 Date Completed: 20081202 Latest Revision: 20231213

20231215

10.1093/jn/138.10.2016S

18806117