Vitamin B-6 Metabolism and Interactions with TNAP

Coburn, Stephen P.

doi:10.1007/978-94-017-7197-9_11

Cited by 17 publications

(11 citation statements)

References 165 publications

(187 reference statements)

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“…In mammals, 70–80% of the vitamin B6 is located in the skeletal muscle, where it functions as co-factor for glycogen phosphorylase [ 35 ]. Further studies are required to appreciate the relation between altered glycogen phosphorylase activity, accumulation of cytoplasmic PAS positive material and clinical hypotonia in GPI-AP defects [ 19 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

Manea

2018

Molecular Genetics and Metabolism Reports

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Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of soluble proteins attached to the external leaflet of the plasma membrane by a post-translation modification, the GPI anchor. The 28 genes currently involved in the synthesis and remodelling of the GPI anchor add to the ever-growing class of congenital glycosylation disorders. Recent advances in next generation sequencing technology have led to the discovery of Mabry disease and CHIME syndrome genetic aetiology. Moreover, with each described mutation known phenotypes expand and new ones emerge without clear genotype-phenotype correlation. A protein database search was made for human GPI-APs with defined pathology to help building-up a physio-pathological mechanism from a clinical perspective. GPI-APs function in vitamin-B6 and folate transport, nucleotide metabolism and lipid homeostasis. Defining GPI-APs role in disease bears significant clinical implications.

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Section: Resultsmentioning

confidence: 99%

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

Manea

2018

Molecular Genetics and Metabolism Reports

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“…). TNAP hydrolyzes extracellular PLP into pyridoxal (PL), which can passively diffuse through the cell membrane (reviewed in Coburn ). Within the cells, PL is rephosphorylated to PLP, which is used as co‐factor of numerous enzymatic reactions (> 60 in mammals, Percudani and Peracchi ).…”

mentioning

confidence: 99%

Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR‐based metabolomics analysis

Cruz

Gleizes

Balayssac

et al. 2017

Journal of Neurochemistry

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Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP’s role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue. For this purpose we used 1H- and 31P NMR to analyze the brain metabolome of Alpl (Akp2) mice null for TNAP function, a well-described model of infantile HPP. Among 39 metabolites identified in brain extracts of one week-old animals, 8 displayed significantly different concentration in Akp2−/− compared to Akp2+/+ and Akp2+/− mice: cystathionine, adenosine, GABA, methionine, histidine, 3-methylhistidine, N-acetylaspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involve TNAP function, in particular through the regulation of ecto-nucleotide levels and of pyridoxal phosphate-dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA, NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype of HPP.

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“…Así, piridoxina, piridoxal y piridoxamina (y el producto metabólico ácido piridóxico) y sus formas fosforiladas se consideran los diferentes vitámeros B 6 ( Fig. 14) (Bowling, 2011;Coburn, 2015).…”

Section: B5 Cuta Y Metalesunclassified

“…Por esas mismas fechas se describió el primer caso de epilepsia genética dependiente de vitamina B 6 en una niña con convulsiones intratables con fármacos antiepilépticos comunes, que pudieron controlarse con piridoxina (Hunt et al, 1954). Dado que el GABA es un neurotransmisor inhibidor de gran importancia en epilepsia cuya síntesis requiere la descarboxilación del glutamato por una descarboxilasa que usa PLP, es común atribuir a una deficiencia cerebral de GABA la epilepsia asociada al déficit de vitamina B 6 , ya sea nutricional (raro, normalmente solo observada en alcohólicos) o genética (Coburn, 2015). De hecho, se han descrito bajos niveles de GABA en el líquido cefalorraquídeo de niños con epilepsia dependiente de piridoxina (Kurlemann et al, 1992).…”

Section: B5 Cuta Y Metalesunclassified

“…La observación de niveles sanguíneos elevados de PLP en esta enfermedad casa con el esquema de la Fig. 15, en el que el cerebro recibe piridoxal derivado de la hidrólisis de PLP sanguíneo mediada por esta fosfatasa, muy abundante en el plexo coroideo (Coburn, 2015). En los pacientes de este proceso la epilepsia controlable por administración de piridoxina es una manifestación temprana y clínicamente muy visible, pero no la más grave (dada su tratabilidad con piridoxina) de un proceso de hipofosfatasia generalizada que suele acabar pronto con la vida del paciente (Plecko, 2013 (Ito et al, 2013;.…”

Section: Glutamato Descarboxilasaunclassified

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Bases estructurales de la señalización y regulación por nitrógeno y procesos asociados.

Agulló¹

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Vitamin B-6 Metabolism and Interactions with TNAP

Cited by 17 publications

References 165 publications

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

A step closer in defining glycosylphosphatidylinositol anchored proteins role in health and glycosylation disorders

Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR‐based metabolomics analysis

Bases estructurales de la señalización y regulación por nitrógeno y procesos asociados.

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