Expression analysis of the aldo-keto reductases involved in the novel biosynthetic pathway of tetrahydrobiopterin in human and mouse tissues.

Abstract:

:Tetrahydrobiopterin (BH(4)) acts as a cofactor of the aromatic amino-acid hydroxylases, and its deficiency may result in hyperphenylalaninemia (HPA) and decreased production of the neurotransmitters. BH(4) is synthesized by sepiapterin reductase (SPR) from 6-pyruvoyl-tetrahydropterin (PPH(4)). A patient with SPR deficiency shows no HPA; however, an SPR knockout mouse exhibits HPA. We have reported on the SPR-unrelated novel biosynthetic pathway from PPH(4) to BH(4) (salvage pathway II) in which 3alpha-hydroxysteroid dehydrogenase type 2 and aldose reductase work in concert. In this study, we performed the expression analysis of both proteins in humans and wild-type mice. The results of expression analysis indicated that salvage pathway II worked in human liver; however, it did not act in human brain or in mouse liver and brain. For this reason, a patient with SPR deficiency may show progressive neurological deterioration without HPA, and SPR knockout mice may exhibit HPA and abnormal locomotion activity.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Hirakawa H,Sawada H,Yamahama Y,Takikawa S,Shintaku H,Hara A,Mase K,Kondo T,Iino T

doi

10.1093/jb/mvp042

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

51-60

issue

1

eissn

0021-924X

issn

1756-2651

pii

mvp042

journal_volume

146

pub_type

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