Folate Metabolism and the Role of Dihydropteridine Reductase (DHPR)
| Autor: | R. J. Leeming, S. Kate Hall |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Crystallography Phenylalanine hydroxylase biology Clinical Biochemistry Glutamate receptor Biopterin Neopterin Dihydropteridine Reductase Biochemistry chemistry.chemical_compound Endocrinology chemistry QD901-999 Dihydrobiopterin Internal medicine medicine biology.protein Molecular Medicine Vitamin B12 Pterin |
| Zdroj: | Pteridines, Vol 17, Iss 4, Pp 101-102 (2006) |
| ISSN: | 2195-4720 0933-4807 |
| DOI: | 10.1515/pteridines.2006.17.4.101 |
| Popis: | That dihydropteridine reductase (DHPR) has a key role to play in folate metabolism in the CNS is made clear by low concentrations of folate species in the CSF and blood of patients with DHPR deficiency. CSF folate concentrations, for reasons not yet explained, are made even lower by administration of folic acid although peripheral total folate concentrations are normalised. The clinical condition deteriorates markedly with folic acid but in contrast improves with 5-formyltetrahydrofolic acid administration (1). Folate metabolism in the CNS differs from that in the periphery in that CSF total folate concentrations are twice that in peripheral plasma whilst vitamin B12 levels are an order of magnitude lower. DHPR is ubiquitous throughout the body and its function in folate metabolism may be explored using peripheral blood samples without recourse to invasive techniques. In DHPR deficiency there is an increase in 7,8-dihydrobiopterin in the peripheral circulation as there is in classical phenylketonuria, i.e., phenylalanine hydroxylase deficiency where there is also significant perturbation of folate metabolism (2). Presumably the same mechanism prevails but folate speciation in DHPR deficiency appears not to have been explored, therefore the precise role of DHPR in folate metabolism remains unclear. With the elegant methods used by Lucock, vide supra (2) and the existence of patients with active DHPR but absence of pterin carbinolamine dehydratase (PCD) activity (see Fig. 1) there is possibility for this to be resolved For normal salvage of quinonoid dihydrobiopterin (and perhaps folates) both PCD and DHPR are required. With inactive PCD, there is moderate transient hyperphenylalaninaemia which does not require treatment but 7-substituted forms of biopterin and neopterin appear (3). We propose that it would be valuable to look at these rare cases to see if 7-folates are also created as this would elucidate further the role of this salvage pathway in folate metabolism. Folates exist in varying polyglutamated forms, have varying configurations at C5 and C10 positions and as fully oxidised, dihydro and tetrahydro forms. The distribution of postulated 7-folates between states of reduction and glutamate numbers could then be compared with normal values. This would be pertinent to normal CNS function and development and long-term health care of patients with DHPR or PCD deficiency, as well as expanding our limited knowledge of these complex metabolic pathways. |
| Databáze: | OpenAIRE |
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