Inborn Errors of Proline Metabolism

Abstract

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.

Proline metabolism and transport in plant development

“…In humans, dOAT deficiency is associated with high ornithine levels in blood and urine (Ramesh et al 1991). Patients suffer from gyrate atrophy, a degenerative disease of the choroid and retina of the eye that leads to blindness (Mitsubuchi et al 2008). …”

Hyperprolinemia as a clue in the diagnosis of a patient with psychiatric manifestations

“…Several disorders in proline metabolism have been identified, such as deficiency of POX or Hyperprolinemia type I (HPI) and deficiency of the activity of D1-P5C dehydrogenase or Hyperprolinemia type II (HPII). Both rare diseases, inherited as autosomal recessive disorders and characterized biochemically by high proline levels [4][5][6]. Although the neuropsychiatric phenotype has been primarily associated with HPII [6,7], a growing number of patients with these features, in particular schizophrenia, have been documented for HPI [8].…”

Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver

“…are asymptomatic [Mitsubuchi et al, 2008]. Beyond that, mild hyperprolinemia is also present in some hepatic disorders, such as alcoholic liver disease [Vargas-Tank et al, 1988] and cirrhosis [Shaw et al, 1984].…”