Perturbed Epidermal Pterin Metabolism in Hermansky–Pudlak Syndrome

摘要: In Hermansky–Pudlak Syndrome (HPS) a mutation in 79.3 kDa transmembrane protein has been shown. The function of this escaped definition so far. This study unveils defective (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH 4 ) de novo synthesis/recycling for cofactor HPS, where activities the key enzyme GTP-cyclohydrolase I are normal range, but total biopterin levels significantly decreased homozygotes (n = 5) compared with unaffected controls 4) (p 0.00001). Phenylalanine hydroxylase and 4a-hydroxy-6BH -dehydratase lower. mRNA all enzymes involved 6BH biosynthesis/recycling feedback regulatory were expressed keratinocytes from homozygotes, heterozygotes, healthy controls. Thioredoxin/thioredoxin reductase can directly control redox status . These allosterically controlled by calcium. Therefore calcium would affect status. HPS these low concomitant uptake, suggesting an extracellular accumulation second messenger. context phenylalanine is subject to phosphorylation/activation calcium/calmodulin activated kinases. it was anticipated that could cellular L-phenylalanine turnover L-tyrosine. A more rapid uptake its L-tyrosine identified human melanocytes 2), enhanced presence 2 × 10 –3 M slower. Based on evidence date, we speculate mutated be primarily maintaining homeostasis patient group.