Neurobiology of Pyridoxine<sup>a</sup>

Dakshinamurti, K.; Paulose, C S; Viswanathan, Mohan; Siow, Yaw L.; Sharma, Sushil; Bolster, R. Bruce

doi:10.1111/j.1749-6632.1990.tb28049.x

Cited by 73 publications

(25 citation statements)

References 42 publications

(11 reference statements)

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“…In Dakshinamurti et al, adult rats were fed PN-supplemented and PN-deficient diets and the PLP concentrations in the brains were documented. In the whole brain of B6-deficient rats, PLP concentrations were 28% reduced, while in their hypothalamus the reduction was 57% compared to PNsupplemented (control) rats (Dakshinamurti et al 1985). These results are in close accordance with the ones presented in this study.…”

Section: Discussionsupporting

confidence: 92%

Vitamin B6 is essential for serine de novo biosynthesis

Ramos

Pras‐Raves

Gerrits

et al. 2017

J of Inher Metab Disea

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Pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.

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Section: Discussionsupporting

confidence: 92%

Vitamin B6 is essential for serine de novo biosynthesis

Ramos

Pras‐Raves

Gerrits

et al. 2017

J of Inher Metab Disea

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“…These substances, which act as coenzymes for transaminase [30] and in the biosynthesis of the neurotransmitters GABA, dopamine, and serotonin, are important for the development and function of the central nervous system [31]. In the present study, we first investigated whether SB properly inhibits HDAC by western blot analysis.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on Increase of Neurogenesis Induced by Pyridoxine and Increase of Neural Proliferation in the Mouse Dentate Gyrus

et al. 2011

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We previously observed that pyridoxine (vitamin B(6)) significantly increased cell proliferation and neuroblast differentiation without any neuronal damage in the hippocampus. In this study, we investigated the effects of sodium butyrate, a histone deacetylase (HDAC) inhibitor which serves as an epigenetic regulator of gene expression, on pyridoxine-induced neural proliferation and neurogenesis induced by the increase of neural proliferation in the mouse dentate gyrus. Sodium butyrate (300 mg/kg, subcutaneously), pyridoxine (350 mg/kg, intraperitoneally), or combination with sodium butyrate were administered to 8-week-old mice twice a day and once a day, respectively, for 14 days. The administration of sodium butyrate significantly increased acetyl-histone H3 levels in the dentate gyrus. Sodium butyrate alone did not show the significant increase of cell proliferation in the dentate gyrus. But, pyridoxine alone significantly increased cell proliferation. Sodium butyrate in combination with pyridoxine robustly enhanced cell proliferation and neurogenesis induced by the increase of neural proliferation in the dentate gyrus, showing that sodium butyrate treatment distinctively enhanced development of neuroblast dendrites. These results indicate that an inhibition of HDAC synergistically promotes neurogenesis induced by a pyridoxine and increase of neural proliferation.

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“…PLP plays an important role in the nervous systems of mammals, as many neurotransmitters such as dopamine, norepinephrine, serotonin, and ␥-aminobutyric acid are synthesized by PLP-dependent enzymes (7). Changes in PLP concentration in cells influence the stability of the nervous system.…”

Section: Pyridoxal-5ј-phosphate (Plp)mentioning

confidence: 99%

Crystal Structure of Brain Pyridoxal Kinase, a Novel Member of the Ribokinase Superfamily

Kwok

Chang

et al. 2002

Journal of Biological Chemistry

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The three-dimensional structures of brain pyridoxal kinase and its complex with the nucleotide ATP have been elucidated in the dimeric form at 2.1 and 2.6 Å, respectively. Results have shown that pyridoxal kinase, as an enzyme obeying random sequential kinetics in catalysis, does not possess a lid shape structure common to all kinases in the ribokinase superfamily. This finding has been shown to be in line with the condition that pyridoxal kinase binds substrates with variable sizes of chemical groups at position 4 of vitamin B 6 and its derivatives. In addition, the enzyme contains a 12-residue peptide loop in the active site for the prevention of premature hydrolysis of ATP. Conserved amino acid residues Asp 118 and Tyr 127 in the peptide loop could be moved to a position covering the nucleotide after its binding so that its chance to hydrolyze in the aqueous environment of the active site was reduced. With respect to the evolutionary trend of kinase enzymes, the existence of this loop in pyridoxal kinase could be classified as an independent category in the ribokinase superfamily according to the structural feature found and mechanism followed in catalysis.

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Neurobiology of Pyridoxine^a

Cited by 73 publications

References 42 publications

Vitamin B6 is essential for serine de novo biosynthesis

Vitamin B6 is essential for serine de novo biosynthesis

Synergistic Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on Increase of Neurogenesis Induced by Pyridoxine and Increase of Neural Proliferation in the Mouse Dentate Gyrus

Crystal Structure of Brain Pyridoxal Kinase, a Novel Member of the Ribokinase Superfamily

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Neurobiology of Pyridoxinea

Cited by 73 publications

References 42 publications

Vitamin B6 is essential for serine de novo biosynthesis

Vitamin B6 is essential for serine de novo biosynthesis

Synergistic Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on Increase of Neurogenesis Induced by Pyridoxine and Increase of Neural Proliferation in the Mouse Dentate Gyrus

Crystal Structure of Brain Pyridoxal Kinase, a Novel Member of the Ribokinase Superfamily

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Neurobiology of Pyridoxine^a