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In vivo evidence for compromised phenylalanine metabolism in vitiligo.

Abstract：

:Human epidermal melanocytes and keratinocytes express mRNA for all enzymes involved in de novo synthesis/recycling of the cofactor (6R) L-erythro 5,6,7,8 tetrahydrobiopterin (6BH4) in normal healthy individuals. An enhanced epidermal de novo synthesis was identified in association with decreased epidermal phenylalanine hydroxylase and 4a carbinolamine dehydratase in patients with vitiligo. The latter event leads to an accumulation of the nonenzymatic isomer (7R) L-erythro 5,6,7,8 tetrahydrobiopterin (7BH4) inhibiting phenylalanine hydroxylase (PAH) with an apparent Ki = 10(-6) M. One consequence of decreased epidermal PAH activities would be a build-up of L-phenylalanine. To substantiate this consideration, FT-Raman spectroscopy was utilised to study in vivo total phenylalanine levels at 1004 cm-1 in involved and uninvolved skin of 23 patients with vitiligo, showing in all cases increased levels of phenylalanine in involved compared to uninvolved skin of the same individual. Additionally the peripheral blood L-phenylalanine turnover was determined over time after a single oral loading with L-phenylalanine in 32 patients (100 mg/kg body weight). All patients demonstrated slower kinetics from L-phenylalanine to L-tyrosine, but 41% of the group showed significantly slower kinetics under these conditions. None of the patients presented peripheral hyperphenylalaninemia without loading. Our results demonstrate for the first time a phenylalanine build-up in the involved epidermis of patients with vitiligo. These data support the earlier observation of a defective epidermal pterin metabolism in this disease.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Schallreuter KU,Zschiesche M,Moore J,Panske A,Hibberts NA,Herrmann FH,Metelmann HR,Sawatzki J

doi

10.1006/bbrc.1997.8107

subject

Has Abstract

pub_date

1998-02-13 00:00:00

pages

395-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(97)98107-9

journal_volume

243

pub_type

杂志文章

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