Molecular mechanisms underlying therapeutic action of vitamin B6

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The aim of the study was to analyze the molecular mechanisms that determine the possibility of using vitamin B6 in clinical practice for the correction of various pathological conditions.

Materials and methods. Information retrieval (Scopus, PubMed) and library (eLibrary) databases were used as research tools. In some cases, the ResearchGate application was used for a semantic search. The analysis and generalization of the scientific literature on the topic of research, covering the period from 1989 to the present, has been carried out in the work.

Results. It has been shown that all chemical forms of vitamin B6 are able to penetrate the membranes of most cells by free diffusion, while forming phosphorylated forms inside. Pyridoxal phosphate is a biologically important metabolite that is directly involved as a cofactor in a variety of intracellular reactions. Requirements for this cofactor depend on the age, sex and condition of the patient. Pregnancy and lactation play a special role in the consumption of vitamin B6. In most cases, a balanced diet will provide an acceptable level of this vitamin. At the same time, its deficiency leads to the development of a number of pathological conditions, including neurodegenerative diseases, inflammations and diabetes. Negative manifestations from the central nervous system are also possible with an excessive consumption of B6.

Conclusion. Replenishment of the vitamin B6 level in case of its identified deficiency is a necessary condition for the successful treatment of the central nervous system diseases, diabetes and correction of patients’ immune status. At the same time, it is necessary to observe a balanced intake of this cofactor in order to avoid negative effects on metabolism in case of its excess.

作者简介

Olga Zagubnaya

Institute of Cytochemistry and Molecular Pharmacology; Biomedical Research Group, BiDiPharma GmbH

Email: oz_brg@icmph.org
ORCID iD: 0000-0001-6623-6938

Junior Researcher, Department of Mathematical Modeling and Statistical Processing of Results, Institute of Cytochemistry and Molecular Pharmacology; Research Fellow, Biomedical Research Group, BiDiPharma GmbH

俄罗斯联邦, Bldg 14, 24, 6th Radialnaya St., Moscow, 115404; 5, Bültbek, Siek, 22962, Germany

Yaroslav Nartsissov

Institute of Cytochemistry and Molecular Pharmacology; Biomedical Research Group, BiDiPharma GmbH

编辑信件的主要联系方式.
Email: yn_brg@icmph.org
ORCID iD: 0000-0001-9020-7686

Candidate of Sciences (Physics and Mathematics), Associate Professor in Biophysics, Head of the Sector of Mathematical Modeling and Statistical Processing of Results, Institute of Cytochemistry and Molecular Pharmacology; Head of Biomedical Research Group, BiDiPharma GmbH

俄罗斯联邦, Bldg 14, 24, 6th Radialnaya St., Moscow, 115404; 5, Bültbek, Siek, 22962, Germany

参考

  1. Shtyrlin YG, Petukhov AS, Strelnik AD, Shtyrlin NV, Iksanova AG, Pugachev MV, Pavelyev RS, Dzyurkevich MS, Garipov MR, Balakin KV. Chemistry of pyridoxine in drug design. Russ Chem Bull. 2019;68(5):911–45. doi: 10.1007/s11172-019-2504-5
  2. Ofoedu CE, Iwouno JO, Ofoedu EO, Ogueke CC, Igwe VS, Agunwah IM, Ofoedum AF, Chacha JS, Muobike OP, Agunbiade AO, Njoku NE, Nwakaudu AA, Odimegwu NE, Ndukauba OE, Ogbonna CU, Naibaho J, Korus M, Okpala COR. Revisiting food-sourced vitamins for consumer diet and health needs: a perspective review, from vitamin classification, metabolic functions, absorption, utilization, to balancing nutritional requirements. PeerJ. 2021 Sep 1;9:e11940. doi: 10.7717/peerj.11940
  3. Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015 Apr 20;6:148. doi: 10.3389/fgene.2015.00148
  4. Ueland PM, McCann A, Midttun Ø, Ulvik A. Inflammation, vitamin B6 and related pathways. Mol Aspects Med. 2017 Feb;53:10–27. doi: 10.1016/j.mam.2016.08.001
  5. Mackey AD, McMahon RJ, Townsend JH, Gregory JF III. Uptake, hydrolysis, and metabolism of pyridoxine-5′-beta-Dglucoside in Caco-2 cells. J Nutr. 2004;134(4):842–6.
  6. Wilson MP, Plecko B, Mills PB, Clayton PT. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis. 2019 Jul;42(4):629–46. doi: 10.1002/jimd.12060
  7. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011 Aug 1;437(3):357–72. doi: 10.1042/BJ20110326
  8. Yamashiro T, Yasujima T, Said HM, Yuasa H. pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates. J Biol Chem. 2020 Dec 11;295(50):16998–17008. doi: 10.1074/jbc.RA120.013610
  9. Bohney JP, Fonda ML, Feldhoff RC. Identification of Lys190 as the primary binding site for pyridoxal 5’-phosphate in human serum albumin. FEBS Lett. 1992 Feb 24;298 (2–3):266–8. doi: 10.1016/0014-5793(92)80073-p
  10. Ueland PM, Ulvik A, Rios-Avila L, Midttun Ø, Gregory JF. Direct and Functional Biomarkers of Vitamin B6 Status. Annu Rev Nutr. 2015;35:33–70. doi: 10.1146/annurev-nutr-071714-034330
  11. Wang HS, Kuo MF. Vitamin B6 related epilepsy during childhood. Chang Gung Med J. 2007 Sep-Oct;30(5):396–401.
  12. Whittaker JW. Intracellular trafficking of the pyridoxal cofactor. Implications for health and metabolic disease. Archives of biochemistry and biophysics. 2016 Feb 15;592:20–6.
  13. Ito T, Ogawa H, Hemmi H, Downs DM, Yoshimura T. Mechanism of Pyridoxine 5’-Phosphate Accumulation in Pyridoxal 5’-Phosphate-Binding Protein Deficiency. J Bacteriol. 2022 Mar 15;204(3):e0052121. doi: 10.1128/JB.00521-21
  14. Du YL, Ryan KS. Pyridoxal phosphate-dependent reactions in the biosynthesis of natural products. Natural Product Reports. 2019;36(3):430–457.
  15. Hoffarth ER, Rothchild KW, Ryan KS. Emergence of oxygen- and pyridoxal phosphate-dependent reactions. FEBS J. 2020 Apr;287(7):1403–28. doi: 10.1111/febs.15277
  16. Bisello G, Longo C, Rossignoli G, Phillips RS, Bertoldi M. Oxygen reactivity with pyridoxal 5’-phosphate enzymes: biochemical implications and functional relevance. Amino Acids. 2020 Aug;52(8):1089–105. doi: 10.1007/s00726-020-02885-6
  17. Dalto DB, Matte JJ. Pyridoxine (Vitamin B₆) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation. Nutrients. 2017 Feb 24;9(3):189. doi: 10.3390/nu9030189
  18. Thaver D, Saeed MA, Bhutta ZA. Pyridoxine (vitamin B6) supplementation in pregnancy. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000179. doi: 10.1002/14651858.CD000179.pub2
  19. Ali MA, Hafez HA, Kamel MA, Ghamry HI, Shukry M, Farag MA. Dietary Vitamin B Complex: Orchestration in Human Nutrition throughout Life with Sex Differences. Nutrients. 2022 Sep 22;14(19):3940. doi: 10.3390/nu14193940
  20. Sharma P, Han SM, Gillies N, Thorstensen EB, Goy M, Barnett MPG, Roy NC, Cameron-Smith D, Milan AM. Circulatory and Urinary B-Vitamin Responses to Multivitamin Supplement Ingestion Differ between Older and Younger Adults. Nutrients. 2020 Nov 17;12(11):3529. doi: 10.3390/nu12113529
  21. Schorgg P, Bärnighausen T, Rohrmann S, Cassidy A, Karavasiloglou N, Kühn T. Vitamin B6 Status among Vegetarians: Findings from a Population-Based Survey. Nutrients. 2021 May 12;13(5):1627. doi: 10.3390/nu13051627
  22. McCormick DB. Two interconnected B vitamins: riboflavin and pyridoxine. Physiol Rev. 1989 Oct;69(4):1170–98. doi: 10.1152/physrev.1989.69.4.1170
  23. Wang D, Wang X, Kong J, Wu J, Lai M. GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures. Epilepsy Res. 2016 Oct;126:83–9. doi: 10.1016/j.eplepsyres.2016.07.003
  24. Nong X, Zhang C, Wang J, Ding P, Ji G, Wu T. The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects. Front Oncol. 2022 Sep 2;12:988290. doi: 10.3389/fonc.2022.988290
  25. Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42 Suppl 3:8–12. doi: 10.1046/j.1528-1157.2001.042suppl.3008.x
  26. Rizzi S, Spagnoli C, Frattini D, Pisani F, Fusco C. Clinical Features in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Systematic Review. Behav Neurol. 2022 Oct 11;2022:2210555. doi: 10.1155/2022/2210555
  27. Wu S, Zhou J, Zhang H, Barger SW. Serine Racemase Expression Differentiates Aging from Alzheimer’s Brain. Curr Alzheimer Res. 2022;19(7):494–502. doi: 10.2174/1567205019666220805105106
  28. Taylor JL, Brown BL. Structural basis for dysregulation of aminolevulinic acid synthase in human disease. J Biol Chem. 2022 Mar;298(3):101643. doi: 10.1016/j.jbc.2022.101643
  29. Lill R, Freibert SA. Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis. Annu Rev Biochem. 2020 Jun 20;89:471–99. doi: 10.1146/annurev-biochem-013118-111540
  30. Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol. 2015 Jan 21;21(3):711–25. doi: 10.3748/wjg.v21.i3.711
  31. Kashii T, Gomi T, Oya T, Ishii Y, Oda H, Maruyama M, Kobayashi M, Masuda T, Yamazaki M, Nagata T, Tsukada K, Nakajima A, Tatsu K, Mori H, Takusagawa F, Ogawa H, Pitot HC. Some biochemical and histochemical properties of human liver serine dehydratase. Int J Biochem Cell Biolog. 2005;37(3):574–89. doi: 10.1016/j.biocel.2004.08.004
  32. Donnier-Maréchal M, Vidal S. Glycogen phosphorylase inhibitors: a patent review (2013–2015). Expert Opin Ther Pat. 2016;26(2):199–212. doi: 10.1517/13543776.2016.1131268
  33. Kaczmarczyk A, Baker M, Diddle J, Yuzyuk T, Valle D, Lindstrom K. A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy. Mol Genet Metab Rep. 2022 Mar 16;31:100857. doi: 10.1016/j.ymgmr.2022.100857
  34. Wang D, Kong J, Wu J, Wang X, Lai M. GC-MS-based metabolomics identifies an amino acid signature of acute ischemic stroke. Neurosci Lett. 2017 Mar 6;642:7–13. doi: 10.1016/j.neulet.2017.01.039
  35. Tanaka M, Tóth F, Polyák H, Szabó Á, Mándi Y, Vécsei L. Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines. 2021 Jun 25;9(7):734. doi: 10.3390/biomedicines9070734
  36. Nartsissov YR. Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications. COVID-19, Neuroimmunology and Neural Function, edited by Thomas Heinbockel, Robert Weissert, IntechOpen; 2022. doi: 10.5772/intechopen.103760
  37. Nartsissov YR. Geometries of vasculature bifurcation can affect the level of trophic damage during formation of a brain ischemic lesion. Biochem Soc Trans. 2017 Oct 15;45(5):1097–103. doi: 10.1042/BST20160418
  38. Nartsissov YR, Tyukina ES, Boronovsky SE, Sheshegova EV. Computer modeling of spatial-time distribution of metabolite concentrations in phantoms of biological objects by example of rat brain pial. Biophysics. 2013;58(5):703–11. doi: 10.1134/S0006350913050102
  39. Nartsissov YR. Application of a multicomponent model of convectional reaction-diffusion to description of glucose gradients in a neurovascular unit. Front Physiol. 2022 Aug 22;13:843473. doi: 10.3389/fphys.2022.843473
  40. Calderón-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther. 2020 Jan;26(1):5–13. doi: 10.1111/cns.13207
  41. Liampas IN, Siokas V, Aloizou AM, Tsouris Z, Dastamani M, Aslanidou P, Brotis A, Dardiotis E. Pyridoxine, folate and cobalamin for migraine: A systematic review. Acta Neurol Scand. 2020 Aug;142(2):108–20. doi: 10.1111/ane.13251
  42. Liampas I, Siokas V, Mentis AA, Aloizou AM, Dastamani M, Tsouris Z, Aslanidou P, Brotis A, Dardiotis E. Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis. Headache. 2020 Sep;60(8):1508–34. doi: 10.1111/head.13892
  43. Dakshinamurti S, Dakshinamurti K. Antihypertensive and neuroprotective actions of pyridoxine and its derivatives. Can J Physiol Pharmacol. 2015 Dec;93(12):1083–90. doi: 10.1139/cjpp-2015-0098
  44. Eichinger S. Homocysteine, vitamin B6 and the risk of recurrent venous thromboembolism. Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):342–4. doi: 10.1159/000083825
  45. Du X, Yang Y, Zhan X, Huang Y, Fu Y, Zhang Z, Liu H, Zhang L, Li Y, Wen Q, Zhou X, Zuo D, Zhou C, Li L, Hu S, Ma L. Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner. J Cell Mol Med. 2020 Nov;24(22):13129–38. doi: 10.1111/jcmm.15917
  46. Gospe SM. Pyridoxine-dependent seizures: findings from recent studies pose new questions. Pediatr Neurol. 2002 Mar;26(3):181–5. doi: 10.1016/s0887-8994(01)00407-6
  47. Gospe SM Jr. Pyridoxine-Dependent Epilepsy – ALDH7A1. 2001 Dec 7 [updated 2022 Sep 22]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022.
  48. Yazdani M, Elgstøen KBP. Is oxidative stress an overlooked player in pyridoxine-dependent epilepsy? A focused review. Seizure. 2021 Oct;91:369–73. doi: 10.1016/j.seizure.2021.07.014
  49. Hassel B, Rogne AG, Hope S. Intellectual Disability Associated With Pyridoxine-Responsive Epilepsies: The Need to Protect Cognitive Development. Front Psychiatry. 2019 Mar 8;10:116. doi: 10.3389/fpsyt.2019.00116
  50. Surtees R, Mills P, Clayton P.Inborn errors affecting vitamin B6 metabolism. Future Neurology. 2006;1(5):615–20. doi: 10.2217/14796708.1.5.615
  51. Machado A, Vural S, Mercimek-Mahmutoglu S. Pyridoxine dependent epilepsy: Seizure onset, seizure types and EEG features. J Pediatric Epilepsy. 2014;3(4):235–40. doi: 10.3233/PEP-14095
  52. Pena IA, MacKenzie A, Van Karnebeek CDM. Current knowledge for pyridoxine-dependent epilepsy: a 2016 update. Expert Rev Endocrinol Metab. 2017 Jan;12(1):5–20. doi: 10.1080/17446651.2017.1273107
  53. Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C, Mercimek-Mahmutoglu S, Hartmann H, Scharer G, Struijs E, Tein I, Jakobs C, Clayton P, Van Hove JL. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab. 2011 Sep-Oct;104(1–2):48–60. doi: 10.1016/j.ymgme.2011.05.014
  54. Mascolo E, Vernì F. Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms. Int J Mol Sci. 2020 May 23;21(10):3669. doi: 10.3390/ijms21103669
  55. Merigliano C, Mascolo E, La Torre M, Saggio I, Vernì F. Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes. Sci Rep. 2018 Jul 30;8(1):11432. doi: 10.1038/s41598-018-29801-z
  56. Gospe SM Jr. Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006 Apr;19(2):148–53. doi: 10.1097/01.wco.0000218230.81301.12
  57. Aufiero E, Stitik TP, Foye PM, Chen B. Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review. Nutr Rev. 2004 Mar;62(3):96–104. doi: 10.1111/j.1753–4887.2004.tb00030.x
  58. AlSaad D, Awaisu A, Elsalem S, Abdulrouf PV, Thomas B, AlHail M. Is pyridoxine effective and safe for post-partum lactation inhibition? A systematic review. J Clin Pharm Ther. 2017 Aug;42(4):373–82. doi: 10.1111/jcpt.12526
  59. Cada DJ, Demaris K, Levien TL, Baker DE. Doxylamine succinate/pyridoxine hydrochloride. Hosp Pharm. 2013 Oct;48(9):762–6. doi: 10.1310/hpj4809-762
  60. Nuangchamnong N, Niebyl J. Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview. Int J Womens Health. 2014 Apr 12;6:401–9. doi: 10.2147/IJWH.S46653
  61. Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin®) for the treatment of nausea and vomiting of pregnancy. Paediatr Drugs. 2014 Jun;16(3):199–211. doi: 10.1007/s40272-014-0065-5
  62. Findling RL, Maxwell K, Scotese-Wojtila L, Huang J, Yamashita T, Wiznitzer M. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. J Autism Dev Disord. 1997 Aug;27(4):467–78. doi: 10.1023/a:1025861522935
  63. Shishkova VN, Nartsissov YR, Titova VY, Sheshegova EV. Molecular mechanisms defining application of glycine and zinc combinationin correction of stress and anxiety main manifestations. Pharmacy & Pharmacology. 2022;10(5):404–15. doi: 10.19163/2307-9266-2022-10-5-404-415
  64. Lian S, Zhang X, Zhang Y, Zhao Q. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy agents: a meta-analysis. Clin Exp Dermatol. 2021 Jun;46(4):629-635. doi: 10.1111/ced.14486
  65. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005 Apr;12(2):78–85. doi: 10.1097/00063110-200504000-00007
  66. Hadtstein F, Vrolijk M. Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity. Adv Nutr. 2021 Oct 1;12(5):1911–29. doi: 10.1093/advances/nmab033
  67. Ghavanini AA, Kimpinski K. Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess. J Clin Neuromuscul Dis. 2014 Sep;16(1):25–31. doi: 10.1097/CND.0000000000000049

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2. Figure 1 – Mutual conversion of three B6 vitamers

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3. Figure 2 – Main ways of transport and tissue distribution of B6 vitamers

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4. Figure 3 – Generalized representation of PLP states in composition of active protein center, taking into account transition of internal aldimine to external, followed by quinonoid formation

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5. Figure 4 – Scheme of mutual influence processes leading to vitamin B6 deficiency and formation of diabetes mellitus

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