title: 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.
authors.affiliation: Department of General Studies, Nihon University, Setagaya-ku, Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sawada
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamahama
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takikawa
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mase
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Iino
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000449:Aldehyde Reductase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology*; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity
chemical_list: D001708:Biopterins; C041361:6-lactoyltetrahydropterin; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; D000449:Aldehyde Reductase; C003402:sapropterin