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In enzymology, a 6-pyruvoyltetrahydropterin synthase (PTPS) (EC 4.2.3.12) is an enzyme that catalyzes the following chemical reaction:

7,8-Dihydroneopterin triphosphate 6-pyruvoyltetrahydropterin + triphosphate

Hence, this enzyme has one substrate, 7,8-Dihydroneopterin triphosphate, and two products, 6-pyruvoyltetrahydropterin and triphosphate.

Enzyme Class

This enzyme belongs to the family of lyases, to be specific, those carbon-oxygen lyases acting on phosphates. The systematic name of this enzyme class is 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming).

Synonyms

Other names in common use include 2-amino-4-oxo-6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-, and dihydroxypteridine triphosphate lyase. This enzyme participates in tetrahydrobiopterin biosynthesis.

Genetics

This enzyme 6-pyruvoyltetrahydropterin synthaseis encoded by the PTS gene.

Structural studies

As of mid-2010, 13 structures have been solved for this class of enzymes, with PDB accession codes 3M0N, 3LZE, 3LX3, 3I2B, 2DTT, 1GTQ, 1B66, 1B6Z, 1Y13, 2A0S, 2DJ6, 2G64, and 2OBA.

References

Milstien S, Kaufman S (1989). "The biosynthesis of tetrahydrobiopterin in rat brain. Purification and characterization of 6-pyruvoyl tetrahydropterin (2'-oxo)reductase". J. Biol. Chem. 264 (14): 8066–73. PMID 2656673.
Thony B, Leimbacher W, Burgisser D, Heizmann CW (1992). "Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme". Biochem. Biophys. Res. Commun. 189 (3): 1437–43. doi:10.1016/0006-291X(92)90235-D. PMID 1282802.

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English Journal

Increase in tetrahydrobiopterin concentration with aging in the cerebral cortex of the senescence-accelerated mouse prone 10 strain caused by abnormal regulation of tetrahydrobiopterin biosynthesis.

Miyajima M1, Minoshima M, Tanaka M, Nishimura R, Hishioka N, Numata T, Hosokawa T, Kurasaki M, Saito T.Author information 1Graduate School of Health Sciences, Hokkaido University, Sapporo, 060-0812, Japan.Abstract6R-L-Erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH) activity and is a risk factor for cognitive decline and brain atrophy. Previous studies have shown that the decline in TH activity in the cerebral cortex of senescence-accelerated mouse prone 10 (SAMP10) mice is caused, at least in part, by a decrease in Fe, ferritin, and TH phosphorylation. We determined the concentrations of BH4 and the enzymes GTP cyclohydrolase-1,6-pyruvoyltetrahydropterin synthase and sepiapterin reductase (SPR) in the de novo pathway of BH4 biosynthesis. Dihydrofolate reductase (DHFR), which converts BH2 to BH4 in the salvage pathway of BH4 synthesis was also determined in the cerebral cortex of SAM mice at 3 and 12 months of age. The BH4 concentration was measured by HPLC, and the protein levels of enzymes involved in BH4 synthesis were measured by western blot analysis. At 12 months of age, BH4 concentration in the cerebral cortex of SAMP10 mice showed significantly higher values as compared to that of control mice. Further, the protein level of SPR in SAMP10 mice was significantly higher than that in SAMR1 mice at 3 and 12 months of age. In contrast to SPR, the protein level of DHFR in SAMP10 mice was significantly lower than that in SAMR1 mice. These results indicate that abnormal regulation of BH4 metabolism occurs in the cerebral cortex of SAMP10 where the dysfunction of the salvage pathway of BH4 synthesis may cause overproduction of BH4 through the de novo pathway, which is considered characteristic in the cerebral cortex of SAMP10 with aging. Therefore, there is a possibility that the excess amounts of BH4 lead to age-related brain dysfunction in the cerebral cortex of SAMP10.
Biogerontology.Biogerontology.2013 Oct;14(5):491-501. doi: 10.1007/s10522-013-9452-5. Epub 2013 Aug 11.
6R-L-Erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH) activity and is a risk factor for cognitive decline and brain atrophy. Previous studies have shown that the decline in TH activity in the cerebral cortex of senescence-accelerated mouse prone 10 (SA
PMID 23933678

Albino (al) is a tetrahydrobiopterin (BH4)-deficient mutant of the silkworm Bombyx mori.

Fujii T1, Abe H, Kawamoto M, Katsuma S, Banno Y, Shimada T.Author information 1Institute of Genetic Resources, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan. fujii.tsuguru.233@m.kyushu-u.ac.jpAbstractAlbino (al) is a lethal mutant of Bombyx mori that exhibits a colourless cuticle after the first ecdysis and dies without feeding on mulberry. Previous studies have indicated that sclerotisation was insufficient because of defective phenylalanine and tyrosine metabolism in albino larvae. However, the genetic mechanism underlying the albino phenotype has not been determined. Dopamine plays a central role in insect cuticle colouration and sclerotisation. The pathway for dopamine biosynthesis from phenylalanine involves phenylalanine hydroxylase (PAH; EC 1.14.16.1) and tyrosine hydroxylase (TH; EC 1.14.16.2). Tetrahydrobiopterin (BH4) is an essential cofactor of aromatic amino acid hydroxylases, including PAH and TH. Thus, BH4 is indispensable for cuticle colouration and sclerotisation. Here we report on identifying mutations in the gene that encodes for the Bombyx homolog of 6-pyruvoyl-tetrahydropterin synthase (PTS) which is involved in the biosynthesis of BH4, in 2 strains with different al alleles. In strain a60 (al), a transposable element was inserted in exon 2 of BmPTS. In strain a61 (al²), an 11-bp deletion was identified in the exon 2 region of BmPTS. After oral administration of BH4 to the al² larvae, the survival rate was effectively increased and the larval integument was pigmented. These results indicated that BmPTS was responsible for the albino mutants of B. mori. We conclude that (i) a mutation in BmPTS leads to an insufficient supply of BH4 and results in defective dopamine biosynthesis and (ii) lack of dopamine results in cuticle colouration and sclerotisation failure. Lemon (lem) is a BH4-deficient mutant. It has been reported that de novo synthesis of zygotic BH4 was indispensable for viability of the embryo in eggs laid by lem (lem/lem¹) females. We found that lem/lem, al²/al² larvae produced by lem (lem/lem) females were viable during the first instar stage, suggesting that al²/al² embryo could synthesis BH4 by using maternally transmitted BmPTS.
Insect biochemistry and molecular biology.Insect Biochem Mol Biol.2013 Jul;43(7):594-600. doi: 10.1016/j.ibmb.2013.03.009. Epub 2013 Apr 6.
Albino (al) is a lethal mutant of Bombyx mori that exhibits a colourless cuticle after the first ecdysis and dies without feeding on mulberry. Previous studies have indicated that sclerotisation was insufficient because of defective phenylalanine and tyrosine metabolism in albino larvae. However, th
PMID 23567588

An international survey of patients with tetrahydrobiopterin deficiencies presenting with hyperphenylalaninaemia.

Opladen T1, Hoffmann GF, Blau N.Author information 1Division of Inborn Metabolic Diseases, University Childrens Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.AbstractOBJECTIVES: The present study summarizes clinical and biochemical findings, current treatment strategies and follow-up in patients with tetrahydrobiopterin (BH(4)) deficiencies.
Journal of inherited metabolic disease.J Inherit Metab Dis.2012 Nov;35(6):963-73. doi: 10.1007/s10545-012-9506-x. Epub 2012 Jun 23.
OBJECTIVES: The present study summarizes clinical and biochemical findings, current treatment strategies and follow-up in patients with tetrahydrobiopterin (BH(4)) deficiencies.METHODS: We analyzed the clinical, biochemical and treatment data of 626 patients with BH(4) deficiencies [355 with 6-pyruv
PMID 22729819

Japanese Journal

Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders : Regulation of Dopaminergic Neural Transmission by Tyrosine Hydroxylase Protein at Nerve Terminals

Sumi-Ichinose Chiho,Ichinose Hiroshi,Ikemoto Kazuhisa [他],NOMURA Takahide,KONDO Kazunao
Journal of pharmacological sciences 114(1), 17-24, 2010-09-20
… 5<I>R</I>-L-Erythro-5,6,7,8-tetrahydrobiopterin (BH<SUB>4</SUB>) is an essential cofactor for tyrosine hydroxylase (TH). …
NAID 10029889595

Catecholamines and serotonin are differently regulated by tetrahydrobiopterin : a study from 6-pyruvoyltetrahydropterin synthase knockout mice

SUMI-ICHINOSE C
J Biol Chem 276, 41150-41160, 2001
NAID 80012719110

Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations

CHIEN YH
J Inherit Metab Dis 24, 815-823, 2001
NAID 30012217590

「6-ピルボイルテトラヒドロプテリンシンターゼ」

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6-pyruvoyltetrahydropterin synthase
Identifiers
EC number	4.2.3.12
CAS number	97089-82-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
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PMC	articles
PubMed	articles
NCBI	proteins