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English Corner – Vit B6: How much is too much?

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English Corner – Vit B6: How much is too much?  Empty English Corner – Vit B6: How much is too much?

Message  Luc Lun 26 Fév 2024 - 9:51

The English Corner – Vit B6: How much is too much? 
Main ideas
- Too much of a good thing is bad. Especially bad for neuro-sensitive people.
- Vitamin B6 is well documented for its role as a modulator of steroid hormones.
- No problem with food intake if not supplemented.
- Maximum RDA target is 25 mg B6.
- There are 6 vitamers and a way-out form through the urine.
- If we want a pharmacological effect, we have to take into account the form of the vitamers.
- The active form is B6 PLP.
- Look at the 6 vitamers form before continuing (figure):
3 basic forms of vitamers B6:
-        PN= pyridoxine
-        PL = pyridoxal
-        PM = pyridoxamine
And their derivative, coupled with a phosphate molecule:
-        PNP = pyridoxine 5’-phosphate
-        PLP = Pyridoxal 5’-Phosphate (active form)
-        PMP = Pyridoxamine 5’-Phosphate
And the form used as a catabolite (excreted in the urine)
-        PA = 4-Pyridoxic acid.
- A tight regulation of the PLP concentration is necessary in the cell: The aldehydes are toxic. A self -regulation and a protective mechanism coexist. But there is a radical side effect: PLP will no longer passes the encephalic barrier. A withdrawal effect will soon take place, with an impact on neurotransmitters.
- PMP is a safer form: PMP is slightly increased in plasma, and rapidly converted into PLP and PL when needed.
- An excess of pyridoxine (PN) is deleterious. No pyridoxine supplement advised: PN has an inhibition effect on PLP, the active form.
- PL could be converted to PN by a PL reductase (side effects when too high supplementation).
- PM could be more suitable for supplementation because of the very low formation of PN by PM.
- If we suffer from a lack of enzymes, we must pay attention to the conversion pathway: PLP as a coenzyme factor has a pivotal role in catalysis of various enzymatic reactions.
- See the roles of PNP-dependent enzymes, namely kinase and oxidase (+ phosphatase).

See figure:
[Vous devez être inscrit et connecté pour voir ce lien]

- This post is being developed. To be continued.


Dernière édition par Luc le Lun 26 Fév 2024 - 19:44, édité 1 fois

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« La pratique, c’est quand tout fonctionne et que personne ne sait pourquoi. »
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English Corner – Vit B6: How much is too much?  Empty PLP as modulator of serotonin and steroid hormones

Message  Luc Lun 26 Fév 2024 - 11:27

Vitamin B6 is well documented for its role as a modulator of steroid hormones
Pyridoxal phosphate (PLP), the active form of Vitamin B6, may interfere with the action of the estrogen receptor (ER) by blocking the hormone-binding and/or DNA-binding site of the ER. (1)
Inadequate intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes. (2) Thus, we’ve got a dual role whenever too short or too high supplemented. Indeed, epidemiological studies and meta-analysis indicate an inverse correlation between vitamin B6 and cancer development. (3) Another hypothesis is that PLP deficiency might cause insulin resistance through an increase of homocysteine due to impairment of enzymes which require PLP as a coenzyme. (4) Incorrect PLP intake could represent a cancer risk factor for diabetic patients, as it enhances DNA damage.  PLP deficiency accompanied by hyperglycemia can lead to DNA damage and may contribute to cancerogenesis. However, mutant cells could be under control thanks to ALA supplement (alpha lipoic acid) and anti-AGEs effects of Vit B6 PLP. (5)
How PLP affects neuro-balance will be more comprehensive when the impact of too much PLP will be discussed. Security pathway (overburdened) leads to side effects. 
Sources and References:
1) Brandy Ellen Cowing. Thesis for Master of Science. 2000
[Vous devez être inscrit et connecté pour voir ce lien]
=> The growth of many breast cancers is stimulated by the action of the hormone estrogen. The results of the study indicate that PL significantly impairs growth of breast cancer cells and may be exerting its effects via a steroid-independent mechanism.
2) The Relationship between Vitamin B6, Diabetes and Cancer
[Vous devez être inscrit et connecté pour voir ce lien]
Chiara Merigliano et al. 2018
3) Vitamin B6 intake and blood PLP levels were inversely correlated with the colorectal cancer risk ([Vous devez être inscrit et connecté pour voir ce lien]). PLP has been proposed to influence carcinogenesis through different pathways including those involved in DNA metabolism, suggesting that antitumor properties of vitamin B6 may be in part due to its protective role against DNA damage ([Vous devez être inscrit et connecté pour voir ce lien]).
4) PLP deficiency might cause insulin resistance through an increase of homocysteine due to impairment of enzymes such as cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CGL), which require PLP as a coenzyme ([Vous devez être inscrit et connecté pour voir ce lien]).
5) AN AGE-rich diet results in ROS accumulation ([Vous devez être inscrit et connecté pour voir ce lien]). AGE formation is at the basis of many diabetic complications ([Vous devez être inscrit et connecté pour voir ce lien][Vous devez être inscrit et connecté pour voir ce lien][Vous devez être inscrit et connecté pour voir ce lien]) and it also can contribute to diabetes onset ([Vous devez être inscrit et connecté pour voir ce lien]). Data are consistent with studies indicating that vitamin B6 is beneficial for diabetes complication as, for example, nephropathy ([Vous devez être inscrit et connecté pour voir ce lien]) and retinopathy ([Vous devez être inscrit et connecté pour voir ce lien]) and with in vivo studies showing that PLP is able to reduce AGE accumulation and protein glycation ([Vous devez être inscrit et connecté pour voir ce lien][Vous devez être inscrit et connecté pour voir ce lien]). How PLP counteracts AGEs is not completely understood.
All evidence suggests the importance to maintain under strict control PLP levels in diabetic patients to avoid the chance to increase DNA damage, which could in turn contribute to cancer initiation and progression.
To be continued.
Next point: A tight regulation of the PLP concentration is necessary in the cell: The aldehydes are toxic.

_________________
LucH

« La pratique, c’est quand tout fonctionne et que personne ne sait pourquoi. »
Albert Einstein

« Dans la vie, il y a 2 catégories d'individus : ceux qui regardent le monde tel qu'il est et se demandent pourquoi; ceux qui imaginent le monde tel qu'il pourrait être et se disent : pourquoi pas ? »
G.B. Shaw.
Luc
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English Corner – Vit B6: How much is too much?  Empty Cellular PLP need to be tightly regulated

Message  Luc Mar 27 Fév 2024 - 9:02

A tight regulation of the PLP concentration is necessary in the cell: The aldehydes are toxic
Excerpt (Translation of a post)
Disturbed signaling of pyridoxal kinase PDXK and PNPO
Why does an excess of B6 or an inadequate enzymatic metabolism cause a problem of neuro-sensitivity? (0)
Here is the confirmation that an excess of B6 PLP can disrupt hormonal signaling. We already knew that an excess of PN (pyridoxine) was deleterious. (1-2) Likewise, a PNPO enzyme deficit prevents the conversion of phosphorylated forms of pyridoxine and pyridoxamine into pyridoxal phosphate (PLP), which is the active form. (3-4)
NB1: PNPO = Pyridoxine 5’-phosphate oxidase. 
PNPO is required for catalyzing PMP or PNP into the active form of B6 (PLP).  Two enzymes are responsible for the salvage pathway: pyridoxal kinase (PL kinase) and pyridoxine 5′-phosphate oxidase (PNP oxidase).
Figure: Human vitamin B6 metabolism.
Note’s editor: “PDX” abbreviation is used for pyridoxal on the below figure.
[Vous devez être inscrit et connecté pour voir ce lien]
PDXK = pyridoxal kinase. PDXP = vitamin B6-specific phosphatase. PNPO = pyridox(am)ine phosphate oxidase
NB2: Salvage pathway = Alternative to form the active B6 PLP.
Below, it will be established – mainly by deduction – that an excess of Pyridoxal will lead to the inhibition of the enzyme PLK (Pyridoxal Kinase). PLK is set out of function via the “Salvage pathway” process. Note that this observation has been “recorded” only in 2021. It was not rigorously established up to then.  But, it already seemed logical / acceptable to me.
Practical consequence: I take 100 mg B6 PLP 1x/d at breakfast, for 5 days. Not the weekend.
Pharmacological dose is up to 250 mg. But we have to distinguish the context:
- 25 mg for neuro-sensitive persons.
- No PNP supplement.
- If taken the active form (PLP) we should mind when taking high dose. I explain:
We must not go beyond the absorption capacity of the body. We are not all equal. If you suffer from inflammation, if you need more antioxidants, you will probably burn more B6. What should be avoided is to approach the limit / the level of an overburdened metabolism. A limit that will be different, depending on the individual.
            As it is always better to feel safe than sorry, I decided to limit the dosage of B6 PLP, because it could bring a hormonal problem beyond a 20-day treatment. There is not really a storage place for the B6. It is still necessary to be able to evacuate the metabolites when we approach the saturation threshold. Indeed, our body has a siding (alternative road), in the event of a reached supply.
Attempted explanation by researchers
In case of supplementation with a high dose of Vit B PLP – activated vitamin B6 – or in the event of upstream malfunction (coupling / decoupling process for the transfer to the cell), a protective mechanism occurs in order to control the cell levels of PLP. (6-7)
Pyridoxal (PL) is inhibited by Pyridoxal Kinase (PLK) during a regulating process related to the B6 metabolism. The inactivation process (inhibition of Vit B6 PLP) is a protective mechanism when there is too much PLP in circulation. The cause remains uncertain; the possibilities would include aldehyde stress from the degraded / neutralized PLP molecule. Pathology mimics then the symptoms of a lack of vitamin B6.
There is also an optimal level to find, which can vary from one person to another person, especially when the impact on serotonin could be a problem. A contribution of 10-20 mg of B6 would then be adequate. But this can evolve according to the expense of B6, storage, ...  
Dr. Eric Berg DC advises 2 x 100 mg of B6, and a contribution of 50 mg of zinc to optimize the impact because if we eat little red meat, this will not work well (zinc deficit). I would add magnesium in 2 times, a very slight touch of vit C (in 2 times of maxi 500 mg), and a complex of Vit B co-enzymed, 2x/wk.
 Sources et références

0. Why does an excess of B6 or an inadequate enzymatic metabolism cause a problem of neuro-sensitivity? (in French).
[Vous devez être inscrit et connecté pour voir ce lien]
1. [Vous devez être inscrit et connecté pour voir ce lien]  2021
Excessive pyridoxine (PN) intake induces neuropathy through the preferential injury of sensory neurons.
2. The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
[Vous devez être inscrit et connecté pour voir ce lien]
The neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5′-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
3.  [Vous devez être inscrit et connecté pour voir ce lien]
4. PLP-dependent transferases
Pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors [4]. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [5].
[Vous devez être inscrit et connecté pour voir ce lien] µ
Imported from [Vous devez être inscrit et connecté pour voir ce lien]
5. The Salvage pathway
DOI: [Vous devez être inscrit et connecté pour voir ce lien]
In animals and human beings, pyridoxal 5'-phosphate (PLP) is recycled from food and from degraded B6-enzymes in a "salvage pathway", which essentially involves two ubiquitous enzymes: an ATP-dependent pyridoxal kinase and an FMN-dependent pyridoxine 5'-phosphate oxidase (oxidase enzyme dependent on FMN, aka B2).
Expressed differently, PNP kinase and PNP oxidase play kinetic roles in regulating the level of PLP formation from other vitamers.
6. The Salvage Pathway
In addition to the direct synthesis of new PNP or PLP, the vitamers are interconvertible via the so called salvage pathway. These conversions are accomplished by the action of either kinases or oxidases [[Vous devez être inscrit et connecté pour voir ce lien],[Vous devez être inscrit et connecté pour voir ce lien],[Vous devez être inscrit et connecté pour voir ce lien]]. The salvage pathway has been best analyzed in E. coli, where it has been shown that two different kinases (EC 2.7.1.35) can phosphorylate PN, PL and PM to their respective 5’-phosphates ([Vous devez être inscrit et connecté pour voir ce lien]). 
7. On the mechanism of Escherichia coli pyridoxal kinase inhibition by pyridoxal and pyridoxal 5′-phosphate
[Vous devez être inscrit et connecté pour voir ce lien]
Martino Luigi di Salvo et al. 2015
Abstract
Pyridoxal 5′-phosphate (PLP), the catalytically active form of vitamin B6, plays a crucial role in several cellular processes. In most organisms, PLP is recycled from nutrients and degraded B6-enzymes in a salvage pathway that involves pyridoxal kinase (PLK), pyridoxine phosphate oxidase and phosphatase activities.

_________________
LucH

« La pratique, c’est quand tout fonctionne et que personne ne sait pourquoi. »
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« Dans la vie, il y a 2 catégories d'individus : ceux qui regardent le monde tel qu'il est et se demandent pourquoi; ceux qui imaginent le monde tel qu'il pourrait être et se disent : pourquoi pas ? »
G.B. Shaw.
Luc
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English Corner – Vit B6: How much is too much?  Empty Pyridoxal reductase as part of the human B6 metabolism

Message  Luc Mar 27 Fév 2024 - 21:36

PL reductase activity
Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism
=> PL reductase reduces PNL / PL in PN as a protective role
PL can also be converted to PN by a PL reductase
NB: What follows has already been discussed. I just want to give more scientific evidences or explanations following these facts.
So that you may only want to read what is underlined if you’re already convinced  Wink
Fig. 1. Metabolic pathways of PM and the other B6 vitamers.
PNP oxidase converts PMP and PNP to PLP if required.
[Vous devez être inscrit et connecté pour voir ce lien]
Fig. 1. Metabolic pathways of PM and the other B6 vitamers.
PM, PL, and PN can all be converted to pyridoxal 50-phosphate (PLP), the biologically active form of vitamin B6.
PM, PL, and PN are converted to their phosphorylated forms by pyridoxal kinase (PK) that phosphorylates the 5’hydroxymethyl group. This reaction is reversible by a phosphatase. Pyridox(am)ine phosphate oxidase (PNPO) converts PMP and PNP to PLP. Recently, it has been shown that PL can also be converted to PN in humans by a pyridoxal reductase [46] (dotted grey arrow, on the left side).
A recent study discovered a pyridoxal reductase as part of the human B6 metabolism. This enzyme is responsible for the reduction of PL to PN, and can explain the small amount of PN in our experiment [46] (Fig. 1). This possibility is supported by the study of Vrolijk et al., who found a small increase of PN in plasma after supplementation with PLP [47].
Fig. 2. Plasma time-concentration plots of PM (pyridoxamine)  and its metabolites after a single oral dose of 200 mg PM and a three daily oral dose of 67 mg PM.
=> PM, PMP, PL, PLP, PN, PNP were measured.
Summary
All vitamers can be converted in presence of the following enzymes:
- With PL Kinase: PM => PMP / …
- With PMP transaminase or PNP oxidase: PMP => PLP
- With PNP oxidase: PNP => PLP. (PNP oxidase needs B2)
All forms except pyridoxic acid[2] and pyritinol can be interconverted. Absorbed pyridoxamine is converted to PMP by pyridoxal kinase, which is further converted to PLP by pyridoxamine-phosphate transaminase or pyridoxine 5′-phosphate oxidase which also catalyzes the conversion of PNP to PLP. Pyridoxine 5′-phosphate oxidase is dependent on flavin mononucleotide (FMN) as a cofactor which is produced from [Vous devez être inscrit et connecté pour voir ce lien](vitamin B2). In this biochemical pathway, dietary vitamin B6 cannot be used without vitamin B2.
Source:
1) Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine
Mathias D.G. Van den Eynde et al.
Elsevier – Clinical Nutrition. 2021
[Vous devez être inscrit et connecté pour voir ce lien]
[46] Ramos RJ, Albersen M, Vringer E, Bosma M, Zwakenberg S, Zwartkruis F, et al. Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism. Biochim Biophys Acta Gen Subj 2019;1863(6):1088e97.
[47] Vrolijk MF, Hageman GJ, van de Koppel S, van Hunsel F, Bast A. Inter-individual differences in pharmacokinetics of vitamin B6: a possible explanation of different sensitivity to its neuropathic effects. PharmaNutrition 2020;12: 100188
Excerpt: & Discussion
In this study we analyzed the pharmacokinetics and metabolization of PM in a substudy of a clinical trial. We first optimized and validated a method for the quantification of vitamin B6 in plasma and urine using UPLC-MS/MS. With this method we found increased levels of PM and the biologically active PLP after PM supplementation, with minimal formation of PN.
PM is a known chemical scavenger of reactive oxygen species and reactive dicarbonyl species such as methylglyoxal (MGO), and has been shown to inhibit the formation of AGEs and ALEs [17,39-42]. Clinical trials in patients with diabetic nephropathy and patients with schizophrenia showed moderate improvements with dosages ranging from 100 mg/day up to 2400 mg/day, with no established adverse effects [21e23]. In addition, after a maximum dose of 11.6 mmol/kg, PM did not cause any clinical signs of neurotoxicity in rats [43]. These studies suggest that PM may target physiological pathways relevant to the progression of metabolic and age-related diseases, without adverse effects.
Although several clinical trials with PM have been performed [21-23], the current study is the first report about of PM metabolization in humans (2021, note’s editor). We showed a rapid uptake and metabolization of the PM supplement. After 30 min, plasma concentrations of PM and PLP were increased. This short lag time is likely explained by the fact that B6 vitamers are water-soluble and are absorbed in the gut by non-saturable passive diffusion of the non-phosphorylated forms [44]. In the first 3 h we saw an increase in plasma PM. PMP is slightly increased in plasma, and rapidly converted into PLP and PL. Indeed, PL showed a strong increase in the first 6 h, and the biologically active PLP showed a plateau phase at its maximum concentration. Both a single dose of 200 mg PM, as well as a three daily dose of 67 mg PM resulted in a steady increase of PM and the biologically active form PLP. The three daily dose resulted in a lower, yet more constant PM concentration during the day. Urine concentrations in both experiment groups showed comparable amounts of PM, PL and PN in the 24 h urine collection. After a 12 h overnight fast, very little was still detectable in the second void urine samples. As expected, large portions of these metabolites were excreted via urine.
In both the single dose and three daily dose experiments, we showed maximum plasma PN concentrations below 15 nmol/L. The upper limit of PN intake according to the current EFSA safety regulations is 25 mg/day [45]. Based on the assumption that 25 mg PN would be taken up completely, in an average blood volume of five liter, the maximum PN concentration would be approximately 30 mmol/L. Thus, the conversion of PM to PN in our study is very low. Nevertheless, the formation of PN is remarkable as previous studies presumed that conversion to PN from metabolites other than PNP was not possible. Since we did not find any impurities in our PM supplements and did not show other B6 vitamers than PM in the supplement, it is most likely that a small portion of the PM supplement is converted to PN. Indeed, a recent study discovered a pyridoxal reductase as part of the human B6 metabolism. This enzyme is responsible for the reduction of PL to PN, and can explain the small amount of PN in our experiment [46] (Fig. 1). This possibility is supported by the study of Vrolijk et al., who found a small increase in plasma PN after supplementation with PLP [47].
Fig. 2. Plasma time-concentration plots of PM and its metabolites after a single oral dose of 200 mg PM (A, B, C, D, and E) and a three daily oral dose of 67 mg PM (F, G, H, I, en J). Black arrows: intake PM supplement. PM: pyridoxamine, PMP: pyridoxamine 50-phosphate, PLP: pyridoxal 50-phosphate, PL: pyridoxal, PN: pyridoxine, PNP: pyridoxine 50-phosphate.
Thus, only a small amount of PM was metabolized to PN, which is very beneficial with regards to potential toxicity of PN. Although vitamin B6 is an important enzymatic cofactor in a wide range of physiological processes [3], it has become clear there is a delicate balance between biochemical activity, and cellular toxicity with vitamin B6 supplementation. The vitamer PN in particular appears to be the main culprit in vitamin B6 toxicity [34,36,37]. PN is the most widely used and available form of vitamin B6 supplementation. It has been demonstrated in vitro experiments that PN induces cell death, while the other vitamers including PM did not [37]. Paradoxically, a supplementation with PN can induce similar pathophysiological effects, as vitamin B6 deficiency. This can be explained by the competitive inhibition of active PLP by PN [35,37].Many clinical studies confirm predominantly neurological side effects of PN, and discourage the use of excessive PN dosages [33,47-52]. Although to a lesser extent, side effects of PLP supplementation have also been reported [53,54].
While both PN and PLP can be vital therapeutics [55], it is clear that treatment is not without health risks. Previous studies encourage the research and application of other B6 vitamers [35,37]. We now showed that PM could be more suitable for supplementation because of the very low formation of PN by PM. Thus, the clinical use of PM could offer several benefits for the treatment of vitamin B6 deficiency, but also for treatment of metabolic diseases in which increased dicarbonyls are involved.
2) Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism
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Rúben J. Ramos et al. June 2019 – BBA.
Highlights
·      Pyridoxine strongly accumulates in CSF of PLP-treated patients, thus suggesting the existence of a PN-forming enzyme;
·      Our in vitro studies show that all mammalian cell lines tested reduce PL to PN in a time- and dose-dependent manner;
·      We expand the number of enzymes with a role in human vitamin B6 metabolism;
·      PL reductase(s) may play an important role in limiting the intracellular accumulation of PL and PLP.
3) PLP reductase activity involved in the salvage of PL
PL/PLP reductase activity involved in the salvage of PL under conditions of high PL and/or unbound PLP concentrations (28)
28. Ramos RJ, Albersen M, Vringer E, Bosma M, Zwakenberg S, Zwartkruis F, Jans JJM, Verhoeven-Duif NM. Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism. Biochim Biophys Acta Gen Subj. 2019;1863:1088–97. [[Vous devez être inscrit et connecté pour voir ce lien]] [[Vous devez être inscrit et connecté pour voir ce lien]]
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We hypothesize a protective role of PL reductase(s) by limiting the intracellular accumulation of PL and PLP.
Vitamin B6 is present in the human body as six interconvertible vitamers: 
PN = Pyridoxine => PNP = PN phosphate
PM = pyridoxamine => PMP = phosphate
PL = Pyridoxal => PLP = PL phosphate (PLP = active form of Vit B6).
+ 4-pyridoxic acid (4-PA) to excrete excess PLP under metabolite forms into urine.
We show evidence for the presence of PL reductase activity in humans. But further studies are needed to identify the responsible protein.
Excess PLP => PLP + ALP enzyme = PL => PL + PL reductase => PN.
Note: ALP = alkaline phosphatase enzyme. Its role is to take the phosphate molecule out.
(PLP is dephosphorylated into compounds).
See the figure on next page or on the link of the study.
*) What is the salvage pathway of pyridoxal 5 phosphate?
In animals, pyridoxal 5'-phosphate is recycled from food and from degraded B6-enzymes in a "salvage pathway", which essentially involves two ubiquitous enzymes: an ATP-dependent pyridoxal kinase and an FMN-dependent pyridoxine 5'-phosphate oxidase.
4) PL can also be converted to PN by a PL reductase
Ito TDowns DM. Pyridoxal reductase, PdxJ, is critical for salvage of pyridoxal in Escherichia coliJ Bacteriol 2020; 202:e00056-20  [Vous devez être inscrit et connecté pour voir ce lien]
DOI: [Vous devez être inscrit et connecté pour voir ce lien]
ASM Journals – Journal of Bacteriology. Vol. 202, No. 12. May 2020
This study demonstrated that PdxJ contributes to PL salvage and catalyzes the irreversible conversion of PL to PN under physiological conditions. Known or identified pathways are shown in solid arrows. Broken arrows indicate unidentified/missing pathways (on the figure).
PdxJ = Pyridoxine 5′-phosphate synthase

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English Corner – Vit B6: How much is too much?  Empty Sensitivity of the brain to B6

Message  Luc Mar 27 Fév 2024 - 21:39

Sensitivity of the brain to B6
Pyridoxal-P plays a major role in the short term regulation of γ-aminobutyric acid (GABA) synthesis in brain, as the GABA-synthesizing enzyme glutamate decarboxylase (GAD) is regulated in part by a tightly controlled cycle that interconverts the hold- and apoenzyme. (…)
Source: Pyridoxal Phosphate, GABA and Seizure Susceptibility.
David L. Martin in “Biochemistry of Vitamin B6 and PQQ.  Conference paper”. (ALS)
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*) Pyridoxal-phosphate binding site
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Description
Pyridoxal phosphate is the active form of vitamin B6 (known as pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [[Vous devez être inscrit et connecté pour voir ce lien]]
PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors [[Vous devez être inscrit et connecté pour voir ce lien]]
Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [[Vous devez être inscrit et connecté pour voir ce lien]]
8. Exploring the pyridoxal 5'-phosphate-dependent enzymes. Mozzarelli A, Bettati S. 6, 275-87, (2006). PMID: [Vous devez être inscrit et connecté pour voir ce lien] 
*) Preventing Vitamin B6-Related Neurotoxicity
DOI: [Vous devez être inscrit et connecté pour voir ce lien] 2022 Pramod Reddy.
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PLP-based supplements are preferred and should be administered weekly in low doses (50-100 mg) to maintain a stable serum PLP level between 30 and 60 nmol/L or 7.4 and 15 μg/L.
PLP-based supplements are preferred over pyridoxine supplements (PN) because of minimal neurotoxicity observed in neuronal cell viability tests.
=> Don’t supplement on a regular basis with PLP. Make pause.

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LucH

« La pratique, c’est quand tout fonctionne et que personne ne sait pourquoi. »
Albert Einstein

« Dans la vie, il y a 2 catégories d'individus : ceux qui regardent le monde tel qu'il est et se demandent pourquoi; ceux qui imaginent le monde tel qu'il pourrait être et se disent : pourquoi pas ? »
G.B. Shaw.
Luc
Luc
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