Ihmisen sepiateriini reduktaasi

https://en.wikipedia.org/wiki/Sepiapterin_reductase
Sepiapterin reductase (SPR)  is an enzyme that in humans is encoded by the SPR gene.^[1][2][3]
Tetrahydrobioteriinin (THB)  synteesissä tarvitava  entsyymi.

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases
. SPR plays an important role in the biosynthesis of tetrahydrobiopterin (BH4, THB) .
http://www.biopku.org/pdf/ponzone1.pdf

Sepiapterin reductase (SPR) catalyzes the chemical reaction
L-erythro-7,8-dihydrobiopterin + NADP+ sepiapterin + NADPH + H+
Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP⁺, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H⁺).
This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP⁺ oxidoreductase. This enzyme participates in folate biosynthesis.

Clinical significance

Sepiapterin reductase deficiency belongs to the rare diseases. The clinical phenotype can include progressive psychomotor retardation, altered tone, seizures, choreoathetosis, temperature instability, hypersalivation, microcephaly, and irritability.

Patients with sepiapterin reductase deficiency also manifest dystonia with diurnal variation, oculogyric crises, tremor, hypersomnolence, oculomotor apraxia, and weakness. ^[5]

 Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

(Tryptofaaniaineenvaihdunnan harhahtiestä  B6 vitamiinin puutteessa lisääntyvä xanthureenihappo (XA) esiintyy neuronissa ja estää  vahvasti sepiapteriinireduktaasia. tekemästä BH4 kehovitamiinia)  

THB Tetrahydrobiopteriini tärkeä koentsyymi neuronissa

https://en.wikipedia.org/wiki/Sepiapterin_reductase
Sepiapterin reductase (SPR)  is an enzyme that in humans is encoded by the SPR gene.^[1][2][3]
Tetrahydrobioteriinin (THB)  synteesissä tarvitava  entsyymi.

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases
. SPR plays an important role in the biosynthesis of tetrahydrobiopterin (BH4, THB) .
http://www.biopku.org/pdf/ponzone1.pdf

Sepiapterin reductase (SPR) catalyzes the chemical reaction
L-erythro-7,8-dihydrobiopterin + NADP+ sepiapterin + NADPH + H+
Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP⁺, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H⁺).
This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP⁺ oxidoreductase. This enzyme participates in folate biosynthesis.
http://www.biopku.org/pdf/ponzone1.pdf

Clinical significance

Sepiapterin reductase deficiency belongs to the rare diseases. The clinical phenotype can include progressive psychomotor retardation, altered tone, seizures, choreoathetosis, temperature instability, hypersalivation, microcephaly, and irritability.

Patients with sepiapterin reductase deficiency also manifest dystonia with diurnal variation, oculogyric crises, tremor, hypersomnolence, oculomotor apraxia, and weakness. ^[5]

 Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

(Tryptofaaniaineenvaihdunnan harhahtiestä  B6 vitamiinin puutteessa lisääntyvä xanthureenihappo (XA) esiintyy neuronissa ja estää  vahvasti sepiapteriinireduktaasia. tekemästä BH4 kehovitamiinia)  

Xantureenihappo neuronissa

http://www.ncbi.nlm.nih.gov/pubmed/27167083

Neuroscience. 2016 May 7. pii: S0306-4522(16)30145-2. doi: 10.1016/j.neuroscience.2016.05.006. [Epub ahead of print]

Xanthurenic acid is localized in neurons in the central nervous system.

Roussel G¹, Bessede A², Klein C³, Maitre M⁴, Mensah-Nyagan AG³.

Author information

Abstract

Kynurenine (KYN)  pathway metabolites (KPM) are thought to be synthesized mainly by non-neuronal cells in the mammalian brain. KPM are of particular interest because several studies demonstrated their implication in various disorders of the nervous system.

 Among KPM is xanthurenic acid (XA) deriving from the catabolism of 3-hydroxykynurenine. Based on its chemical structure, XA appears as a close analog of kynurenic acid (KYNA)  which has been extensively investigated and is considered as a potent neuroprotective compound.

Contrary to kynurenine acid, XA has received little attention and its role in the brain remains not elucidated.

We have previously described several characteristics of XA, suggesting its possible involvement in neurotransmission. XA is also proposed as a potential modulator at glutamatergic synapses.

 Here, we used a selective antibody against XA and various neuronal, glial and synaptic markers to show that XA is essentially localized in the soma and dendrites of brain neurons, but is absent from axonal compartments and terminal endings. Our results also reveal that XA-like immunoreactivity is not expressed by glial cells.

 To double-check our findings, we have also used another XA antibody obtained from a commercial source to confirm the neuronal expression of XA. Together, our results suggest that, differently to several other KPM produced by glial cells, XA exhibits a neuronal distribution in the mouse brain.
Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

immunocytochemistry; kynurenine pathway; mouse brain; neuronal localization; xanthurenic acid


Xanthureenihappo  on vahva inhibiittori entsyymille sepiapteriinireduktaasi (SPR), jota tarvitaan  tetrahydrobiopteriinin  de novo synteesiin.