Inborn errors of proline metabolism.
Hiroshi Mitsubuchi1, Kimitoshi Nakamura, Shiro Matsumoto
1Department of Pediatrics, Kumamoto University Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556, Japan.
The Journal of Nutrition
|September 23, 2008
Summary
Inborn errors of proline metabolism, like hyperprolinemia, disrupt proline balance due to enzyme deficiencies. These conditions, including P5C metabolism disorders, can lead to various health issues.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Proline concentration is regulated by proline dehydrogenase (POX) and Delta-1-pyrroline-5-carboxylate (P5C) reductase enzyme balance.
- Inborn errors in proline and P5C metabolism disrupt proline homeostasis, leading to various clinical manifestations.
- Specific genetic loci, such as the PRODH gene on chromosome 22, are implicated in hyperprolinemia type I and associated syndromes like velo-cardio-facial syndrome and schizophrenia susceptibility.
Purpose of the Study:
- To review and summarize the spectrum of inborn errors of proline metabolism.
- To highlight the enzymatic basis and clinical consequences of different proline metabolic disorders.
- To discuss the genetic underpinnings and associated conditions linked to proline metabolism defects.
Main Methods:
- Literature review of inborn errors of proline metabolism.
- Analysis of enzymatic deficiencies and their impact on proline levels.
- Correlation of genetic loci with metabolic disorders and associated syndromes.
Main Results:
- Hyperprolinemia type I (HPI) results from POX deficiency, linked to chromosome 22 deletions and schizophrenia.
- Hyperprolinemia type II (HPII) is caused by P5C dehydrogenase deficiency.
- Hypoprolinemia is associated with P5C synthetase deficiency, leading to hyperammonemia and other amino acid level disturbances.
- Hyperhydroxyprolinemia, a benign disorder, stems from hydroxyproline oxidase deficiency.
- Ornithine aminotransferase deficiency causes transient hyperammonemia and later retinal degeneration (gyrate atrophy).
- Prolidase deficiency, a rare disorder, can cause intellectual disability and skin ulcers.
Conclusions:
- Inborn errors of proline metabolism encompass a range of disorders with diverse enzymatic causes and clinical outcomes.
- Understanding these metabolic pathways and genetic links is crucial for diagnosis and management.
- Disruptions in proline metabolism highlight its importance in physiological processes and disease pathogenesis.
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