Discovery of a new tetrahydrobiopterin-synthesizing enzyme in the lemon mutant of the silkworm Bombyx mori

Iino, Teruhiko; Sawada, Hiroshi; Tsusué, Motoo; Takikawa, Shin-Ichiro

doi:10.1016/s0167-4838(96)00087-8

Cited by 9 publications

(8 citation statements)

References 33 publications

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“…However, Bonafe et al (1) showed that the compensation might be true for some peripheral tissues but not for the brain. Similarly, in the silkworm, Iino et al (29,30) discovered two carbonyl enzymes in the fat body and integument, which could reduce PTP to form BH4. However, the BH4 forming activity in the lem mutant was 10-fold lower than in the normal strain (29).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in the silkworm, Iino et al (29,30) discovered two carbonyl enzymes in the fat body and integument, which could reduce PTP to form BH4. However, the BH4 forming activity in the lem mutant was 10-fold lower than in the normal strain (29). These studies indicate that the salvage pathways cannot provide sufficient BH4, unlike the BH4 biosynthesis pathway catalyzed by SPR.…”

Section: Discussionmentioning

confidence: 99%

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The Silkworm Mutant lemon (lemon lethal) Is a Potential Insect Model for Human Sepiapterin Reductase Deficiency

Meng

Katsuma

Daimon

et al. 2009

Journal of Biological Chemistry

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Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic acid hydroxylases, which control the levels of monoamine neurotransmitters. BH4 deficiency has been associated with many neuropsychological disorders. An inherited defect in BH4 biosynthesis is caused by the deficiency of sepiapterin reductase (SPR), which catalyzes the biosynthesis of BH4 from guanosine triphosphate at the terminal step. The human SPR gene has been mapped at the PARK3 locus, which is related to the onset of Parkinson disease. In this study, we report that mutant strains, lemon (lem) and its lethal allele lemon lethal (lem 1 ) with yellow body coloration, of the silkworm Bombyx mori could be used as the first insect model for human SPR deficiency diseases. We demonstrated that mutations in the SPR gene (BmSpr) were responsible for the irregular body coloration of lem and lem l . Moreover, biochemical analysis revealed that SPR activity in lem l larvae was almost completely diminished, resulting in a lethal phenotype that the larvae cannot feed and that die immediately after the first ecdysis. Oral administration of BH4 and dopamine to lem l larvae effectively increased their survival rates and feeding abilities. Our data demonstrate that BmSPR plays a crucial role in the generation of BH4, and monoamine neurotransmitters in silkworms and the lem (lem l ) mutant strains will be an invaluable resource to address many questions regarding SPR and BH4 deficiencies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Silkworm Mutant lemon (lemon lethal) Is a Potential Insect Model for Human Sepiapterin Reductase Deficiency

Meng

Katsuma

Daimon

et al. 2009

Journal of Biological Chemistry

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“…Sepiapterin reductase is known to be essential for the biosynthesis of tetrahydrobiopterin, a key substance in the biosynthesis of catecholamine and indolamine in vertebrates (Smith, 1987), though another tetrahydrobiopterin-synthesizing enzyme has recently been shown to exist in the silkworm Bombyx mori (Iino et al, 1996). If the enzyme activities involved in the metabolism of sepiapterin are higher in pteridine granules of older A. vulgare adults than in those of younger adults, it could result in older adults having less sepiapterin per mg body weight than younger adults and to contain more biopterin per mg body weight in the pteridine granules than the latter.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Pteridines in the Body Coloration of the Isopod Armadillidium vulgare

Negishi

Hasegawa

Katoh

1998

Pigment Cell Research

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The pteridine content was measured as a function of age in Armadillidium vulgare, and the fine structure of the pteridine-containing granules in the integument was examined in relation to pteridine content. Yellow chromatophores are an essential component of the cream-markings, which are a defining feature of the female A. vulgare. Four kinds of pteridines in the integument including a yellow pigment (sepiapterin) were determined by HPLC. The body color of the red phenotype of A. vulgare varies from dark red to yellowish red and was formerly thought to be due to the quality and quantity of ommochrome pigment. Our analysis of the pteridine content in the integument of this phenotype revealed a significant change in sepiapterin content per body weight with age. Sepiapterin content per body weight decreased gradually with age, while that of biopterin tended to increase with age. Ultrastructural observations of the pigment granules in the yellow chromatophores revealed a corresponding change in the fine structure of pigment granules. In the older adults, some of the electron-dense fibrous materials in the pteridine-containing granules was concentrically arranged, and in the younger adults, most of pteridine-containing granules were electron-lucent. The role of pteridine quality in determining the structure of pteridine-containing granules is discussed.

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“…Dihydroneopterin triphosphate (NH 2 TP) was synthesized enzymatically from GTP by the method of Yoshioka et al (17) using purified GTP cyclohydrolase I from chicken liver ( 1 8). The 1 '-OXPH 4 standard was prepared as described previously (13). The PPH4 synthase was purified from chicken liver by the method of Takikawa et al [19].…”

Section: Methodsmentioning

confidence: 99%

“…We previously discovered two carbonyl reductases (CRI and CRII) that are involved in the formation of BH 4 from PPH 4 in the fat body of the lemon mutant and the normal strain of the silkworm, Bombyx mori (13)(14)(15). The silkworm carbonyl reductases differ from SPR and human carbonyl reductase because CRI catalyzes the reduction of the 2'-keto group of both PPH 4 and 2'-OXPH 4 and CRII reduces the l'-keto group of PPH 4 and Γ-ΟΧΡΗ 4 ( 1 5).…”

Section: Introductionmentioning

confidence: 99%

Possibility of the Nonenzymatic Conversion of 6-(1'-Oxo-2'-hydroxypropyl)- Tetrahydropterin to Sepiapterin

et al. 2005

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Tetrahydrobiopterin (BH 4 ) is a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase. The biosynthetic pathway of BH 4 from 6-pyruvoyl-tetrahydropterin (PPH 4 ) includes two reduction steps catalyzed by sepiapterin rcductasc (SPR). PP1I 4 is reduced to 6-( 1 '-oxo-2'-hydroxypiOpyl)-tetrahydropterin (l'-OXPH 4 ) or 6-( r-hydroxy-2'-oxopropyl)-tetrahydropterin (2'-OXPH 4 ), which is further converted to BH 4 . However, patients with SPR deficiency show normal urinary excretion of pterins without hyperphenylalaninemia, suggesting the existence of another BH 4 biosynthetic pathway, which is not concerned with SPR in humans. Blau et al. proposed a BH 4 biosynthetic salvage pathway containing nonenzymatic conversion of l'-OXPH 4 to sepiapterin. In this study, the possibility of the nonenzymatic conversion of l'-OXPH 4 to sepiapterin was examined by using silkworm carbonyl reductase (CR 1) and human monomeric carbonyl reductase. Since l'-OXPH 4 has been suggested to be nonenzymatically converted into sepiapterin, in an incubation mixture containing PPH 4 and silkworm CR I, sepiapterin was determined by its derivative as biopterin. No sepiapterin was detected in the incubation mixture when the mixture, containing 800 pmol of l'-OXPH 4 , was further incubated at 37°C for 2 h in darkness. This result suggests that the rate of nonenzymatic formation of sepiapterin from l'-OXPH 4 is quite low. The findings obtained here indicate that the proposed pathway in which a nonenzymatic conversion of l'-OXPH 4 to sepiapterin occurs may be difficult or unlikely to proceed in humans.

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Discovery of a new tetrahydrobiopterin-synthesizing enzyme in the lemon mutant of the silkworm Bombyx mori

Cited by 9 publications

References 33 publications

The Silkworm Mutant lemon (lemon lethal) Is a Potential Insect Model for Human Sepiapterin Reductase Deficiency

The Silkworm Mutant lemon (lemon lethal) Is a Potential Insect Model for Human Sepiapterin Reductase Deficiency

Involvement of Pteridines in the Body Coloration of the Isopod Armadillidium vulgare

Possibility of the Nonenzymatic Conversion of 6-(1'-Oxo-2'-hydroxypropyl)- Tetrahydropterin to Sepiapterin

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