{ "id": "ept73btxta", "slug": "pyridoxal-phosphate", "title": "Pyridoxal phosphate", "updated": "2026-10-21", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.biology", "label": "Biological foundations", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology" }, { "id": "life.biology.biochemistry", "label": "Biochemistry and metabolism", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology.biochemistry" }, { "id": "life.biology.biochemistry.molecules", "label": "Metabolites, cofactors, and biomolecules", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology.biochemistry.molecules" }, { "id": "life.biology.biochemistry.molecules.coenzymes-cofactors", "label": "Coenzymes and cofactors", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology.biochemistry.molecules.coenzymes-cofactors" }, { "id": "life.biology.biochemistry.molecules.coenzymes-cofactors.vitamin-derived-coenzymes", "label": "Vitamin-derived coenzymes", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology.biochemistry.molecules.coenzymes-cofactors.vitamin-derived-coenzymes" }, { "id": "life.biology.biochemistry.molecules.coenzymes-cofactors.pyridoxal-phosphate", "label": "Pyridoxal phosphate", "api_url": "https://www.edgepedia.org/api/v1/topics/life.biology.biochemistry.molecules.coenzymes-cofactors.pyridoxal-phosphate" } ], "geo": [ { "id": "geo.us.t1800.life.biology.biochemistry", "label": "United States · 1800 to 1945: Biochemistry and metabolism", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1800.life.biology.biochemistry", "path": [ { "id": "geo.us", "label": "United States", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us" }, { "id": "geo.us.t1800", "label": "United States · 1800 to 1945", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1800" }, { "id": "geo.us.t1800.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1800.life" }, { "id": "geo.us.t1800.life.biology", "label": "Biological foundations", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1800.life.biology" }, { "id": "geo.us.t1800.life.biology.biochemistry", "label": "Biochemistry and metabolism", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1800.life.biology.biochemistry" } ] }, { "id": "geo.us.t1946.life.biology.biochemistry", "label": "United States · 1946 to 2000: Biochemistry and metabolism", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.biology.biochemistry", "path": [ { "id": "geo.us", "label": "United States", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us" }, { "id": "geo.us.t1946", "label": "United States · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946" }, { "id": "geo.us.t1946.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life" }, { "id": "geo.us.t1946.life.biology", "label": "Biological foundations", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.biology" }, { "id": "geo.us.t1946.life.biology.biochemistry", "label": "Biochemistry and metabolism", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.us.t1946.life.biology.biochemistry" } ] } ], "excerpt": "Pyridoxal phosphate (PLP, pyridoxal 5′-phosphate) is the active coenzyme form of vitamin B6, serving over 140 EC-classified enzyme activities in transamination, decarboxylation, and related amino acid reactions via an external aldimine intermediate.", "snippet": "Pyridoxal phosphate (PLP, pyridoxal 5′-phosphate) is the active coenzyme form of vitamin B6, serving over 140 EC-classified enzyme activities in transamination, decarboxylation, and related amino acid reactions via an external aldimine intermediate.", "node": "life.biology.biochemistry.molecules.coenzymes-cofactors.pyridoxal-phosphate", "markdown": "# Pyridoxal phosphate\n\n**Pyridoxal phosphate** (PLP), also called pyridoxal 5′-phosphate, is the biologically active coenzyme form of vitamin B6 and one of the most versatile organic cofactors in biology. It is a derivative of pyridoxal in which phosphoric acid is esterified with the primary hydroxy group, giving the formula C₈H₁₀NO₆P and an average mass of 247.143[1](https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3A18405). Enzymes that use PLP catalyze transamination, decarboxylation, deamination, racemization, elimination, retro-aldol cleavage, and Claisen-like condensation reactions, chiefly on amino acid and amine substrates[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/) • [3](https://openalex.org/W2920573059). More than 140 distinct enzymatic activities cataloged by the Enzyme Commission are PLP-dependent, corresponding to about 4% of all classified activities[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/), and one review counts PLP as a cofactor in over 160 enzyme activities[5](https://pubmed.ncbi.nlm.nih.gov/22201923/).\n\n| Key fact | Detail |\n|---|---|\n| Identity | Monophosphate ester of pyridoxal; formula C₈H₁₀NO₆P, average mass 247.143, CAS 54-47-7[1](https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3A18405) |\n| Role | Active coenzyme form of vitamin B6; cofactor for more than 140 EC-cataloged activities, about 4% of all classified enzyme activities[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/) • [6](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) |\n| Common step | Every PLP-catalyzed reaction begins with formation of an external aldimine (Schiff base) between substrate and PLP[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/) |\n| Chemical basis | The pyridine ring with conjugated double bonds acts as an electron sink, stabilizing carbanionic intermediates through resonance[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/) |\n| Human supply | Recycled through a salvage pathway requiring pyridoxal kinase, pyridoxine 5′-phosphate oxidase, and phosphatases[5](https://pubmed.ncbi.nlm.nih.gov/22201923/) |\n| Genomic footprint | In many free-living prokaryotes almost 1.5% of all genes encode PLP-dependent enzymes; the fraction is lower in higher eukaryotes[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/) |\n| Clinical marker | Plasma PLP is the most common measure of vitamin B6 status; the Food and Nutrition Board used 20 nmol/L as the adequacy indicator for adult RDAs[6](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) |\n\n## Chemical mechanism\n\nPLP consists of a central pyridine ring bearing four substituents at the 2′ to 5′ positions: methyl, hydroxyl, formyl, and phosphomethyl groups[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/). The ring's conjugated double bonds and its ring nitrogen allow electron movement to extend through the Schiff-base linkage to substrates, so PLP works as an efficient electron sink that stabilizes the carbanionic intermediates of substrates through its quinonoid structure[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/).\n\nThe first and common step in all PLP-catalyzed reactions is formation of an external aldimine intermediate. The unprotonated amino group of the substrate attacks the protonated [Schiff base](https://www.edgepedia.org/schiff-base) formed between an active-site lysine and the aldehyde group of PLP; after proton transfers and collapse, a Schiff base links the substrate directly to PLP[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/). From this shared intermediate the different reaction types diverge, and the enzyme's active-site residues determine which bond of the substrate is broken[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/). Reaction specificity is shaped by [stereoelectronic effects](https://www.edgepedia.org/stereoelectronic-effect), the protonation state of the external aldimine, and the interaction of the carbanionic intermediate with protein side chains in the active site[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/).\n\nThis shared chemistry has a cost: the high reactivity of PLP permits catalytic promiscuity, meaning a single enzyme can catalyze different chemical reactions, and relatively low specificity complicates the design of drugs against PLP-dependent enzymes[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/). The phosphate group also matters structurally; replacing PLP with pyridoxal in serine palmitoyltransferase lowered enzyme activity more than 10-fold even though transaldimination still proceeded[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC6411801/).\n\n## Reaction repertoire\n\nPLP enzymes catalyze racemization, transamination, decarboxylation, elimination, retro-aldol cleavage, [Claisen condensation](https://www.edgepedia.org/claisen-condensation), and other reactions on substrates containing an amino group, most commonly α-amino acids[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/). In aminotransferases, PLP undergoes reversible conversion into pyridoxamine 5′-phosphate (PMP), which has coenzyme activity for the aminotransferases but not for other types of vitamin B6-dependent enzymes[9](https://iupac.qmul.ac.uk/misc/B6.html).\n\nThe repertoire keeps expanding. A small number of PLP-dependent enzymes employ molecular oxygen as a cosubstrate, and these enzymes occur in multiple protein families, suggesting that reaction with oxygen emerged de novo several times[10](https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15277). In natural product biosynthesis, PLP-dependent enzymes carry out transaminations, Claisen-like condensations, β- and γ-eliminations and substitutions, epimerizations, decarboxylations, and transaldolations[11](https://pubs.rsc.org/en/content/articlelanding/2019/np/c8np00049b). As of 2023, no PLP-dependent enzyme was known to catalyze Mannich-type reactions until the report of the PLP-dependent Mannich cyclase LolT[12](https://www.nature.com/articles/s41929-023-00963-y).\n\n## Evolution and distribution\n\nPLP-dependent enzymes occur in all organisms and are indispensable in the biosynthesis and degradation of amino compounds[13](https://pubs.acs.org/doi/10.1021/acsinfecdis.5c00996). A genomic survey found that in many free-living prokaryotes almost 1.5% of all genes code for PLP-dependent enzymes, while in higher eukaryotes the percentage is substantially lower, consistent with these catalysts being involved mainly in basic metabolism[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/). Most PLP-dependent enzymes can be assigned to one of three families of homologous proteins, designated the α, β, and γ families by regiospecificity, although alanine racemase, selenocysteine synthase, and many amino acid decarboxylases fall outside them[14](https://pubmed.ncbi.nlm.nih.gov/8112347/). The largest family is the type I, or aminotransferase, superfamily[15](https://www.sciencedirect.com/science/article/abs/pii/S1570963915000114).\n\nBecause their catalytic mechanisms almost invariably involve cofactor-stabilized carbanionic intermediates, enzymes with identical or highly similar activities have apparently arisen several times during evolution, and catalytic promiscuity implies that an organism can have more PLP-dependent activities than it has genes for PLP-dependent enzymes[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/). The genome of *Mycobacterium tuberculosis* encodes 45 bona fide PLP-dependent enzymes, several of them central to the bacterium's survival and pathogenicity and some targeted by the extant drug D-cycloserine[13](https://pubs.acs.org/doi/10.1021/acsinfecdis.5c00996).\n\n## Biosynthesis, salvage, and metabolism\n\nTwo distinct routes produce PLP from scratch, the DXP-dependent route and the R5P route, and the cofactor may likewise be obtained through salvage from the surroundings; among the small number of cofactors whose breakdown has been thoroughly worked out, PLP counts as one.[16](https://pubmed.ncbi.nlm.nih.gov/21767669/) PLP also functions as a singlet oxygen scavenger and has protective effects against oxidative stress in fungi[16](https://pubmed.ncbi.nlm.nih.gov/21767669/).\n\nIn humans, PLP is recycled from food and from degraded PLP-dependent enzymes in a salvage pathway requiring pyridoxal kinase, pyridoxine 5′-phosphate oxidase, and phosphatases; once made, PLP is targeted to the dozens of apoenzymes that need it[5](https://pubmed.ncbi.nlm.nih.gov/22201923/). Of the six interconvertible vitamin B6 vitamers, PLP and pyridoxamine 5′-phosphate are the active coenzyme forms[6](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/). Plasma PLP is the most common measure of vitamin B6 status, with 20 nmol/L used as the adequacy indicator for calculating adult RDAs, although PLP has limitations as a biomarker because inflammation lowers plasma concentrations[6](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) • [17](https://www.ncbi.nlm.nih.gov/books/NBK525313/).\n\n## Medical relevance\n\nBecause PLP is essential for neurotransmitter synthesis and degradation, including the conversion of glutamate into gamma-aminobutyric acid (GABA) and of levodopa into dopamine, inborn errors that reduce intracellular PLP manifest as vitamin B6-responsive epilepsy, usually of early onset[18](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/pyridoxal-phosphate) • [19](https://pubmed.ncbi.nlm.nih.gov/30671974/). Such disorders include pyridox(am)ine phosphate oxidase (PNPO) deficiency, hypophosphatasia, PLP-binding protein (PLPBP) deficiency, and disorders in which metabolites accumulate that inactivate PLP, such as ALDH7A1 deficiency and hyperprolinemia type II[19](https://pubmed.ncbi.nlm.nih.gov/30671974/). In a systematic review of PNPO deficiency covering 49 patients treated with PLP, clinical seizure responsiveness was observed in 38 patients (77.6%), and PLP treatment significantly improved survival compared with untreated siblings of similar phenotype[20](https://pmc.ncbi.nlm.nih.gov/articles/PMC12317649/).\n\nThe metabolic roles of PLP-dependent enzymes also drive inhibitor design. Many PLP-dependent enzymes are current drug targets, and others are envisaged for therapeutic intervention[21](https://onlinelibrary.wiley.com/doi/toc/10.1155/2738.si.536838). Current PLP-enzyme-targeting drugs mimic the PLP-attacking amino group of a substrate, and the [Parkinson's disease](https://www.edgepedia.org/parkinsons-disease) drugs carbidopa and benserazide illustrate the specificity problems such strategies face[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/).\n\n## History\n\nIn 1934, Paul György showed that the factor curing \"rat acrodynia\", a condition of severe cutaneous lesions in young rats, was vitamin B6[22](https://www.ars.usda.gov/research/publications/publication/?seqNo115=307845). Samuel Lepkovsky isolated and crystallized vitamin B6 in 1938, and the following year Leslie Harris and Karl Folkers, and [Richard Kuhn](https://www.edgepedia.org/richard-kuhn) and his associates, independently showed it to be a pyridine derivative, for which György proposed the term pyridoxine[22](https://www.ars.usda.gov/research/publications/publication/?seqNo115=307845). Esmond Snell developed a microbiological growth assay in 1942 that led to the characterization of pyridoxamine and pyridoxal, and further studies showed that pyridoxal, pyridoxamine, and pyridoxine owe their vitamin activity to the organism's ability to convert them into the enzymatically active form pyridoxal 5′-phosphate[22](https://www.ars.usda.gov/research/publications/publication/?seqNo115=307845).\n\n## References\n\n1. [Pyridoxal 5′-phosphate (CHEBI:18405), ChEBI](https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3A18405)\n2. [Controlling reaction specificity in pyridoxal phosphate enzymes, Biochimica et Biophysica Acta](https://pmc.ncbi.nlm.nih.gov/articles/PMC3359020/)\n3. [Current Advances on Structure-Function Relationships of Pyridoxal 5′-Phosphate-Dependent Enzymes (OpenAlex record)](https://openalex.org/W2920573059)\n4. [A genomic overview of pyridoxal-phosphate-dependent enzymes, The EMBO Journal](https://pmc.ncbi.nlm.nih.gov/articles/PMC1326353/)\n5. [Biomedical aspects of pyridoxal 5′-phosphate availability, PubMed](https://pubmed.ncbi.nlm.nih.gov/22201923/)\n6. [Vitamin B6, Health Professional Fact Sheet, NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/)\n7. [Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes](https://pmc.ncbi.nlm.nih.gov/articles/PMC9537024/)\n8. [Current Advances on Structure-Function Relationships of Pyridoxal 5′-Phosphate-Dependent Enzymes, Frontiers in Molecular Biosciences](https://pmc.ncbi.nlm.nih.gov/articles/PMC6411801/)\n9. [Vitamin B-6, IUPAC](https://iupac.qmul.ac.uk/misc/B6.html)\n10. [Emergence of oxygen- and pyridoxal phosphate-dependent reactions, The FEBS Journal](https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15277)\n11. [Pyridoxal phosphate-dependent reactions in the biosynthesis of natural products, Natural Product Reports](https://pubs.rsc.org/en/content/articlelanding/2019/np/c8np00049b)\n12. [A pyridoxal 5′-phosphate-dependent Mannich cyclase, Nature Catalysis](https://www.nature.com/articles/s41929-023-00963-y)\n13. [The Pyridoxal-5′-Phosphate-Dependent Enzymes of Mycobacterium tuberculosis, ACS Infectious Diseases](https://pubs.acs.org/doi/10.1021/acsinfecdis.5c00996)\n14. [Evolutionary relationships among pyridoxal-5′-phosphate-dependent enzymes, PubMed](https://pubmed.ncbi.nlm.nih.gov/8112347/)\n15. [Chemistry and diversity of pyridoxal-5′-phosphate dependent enzymes, Biochimica et Biophysica Acta](https://www.sciencedirect.com/science/article/abs/pii/S1570963915000114)\n16. [Pyridoxal phosphate: biosynthesis and catabolism, PubMed](https://pubmed.ncbi.nlm.nih.gov/21767669/)\n17. [Disease-Induced Deficiency and Conditionally Essential Nutrients in Disease, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK525313/)\n18. [Definition of pyridoxal phosphate, NCI Drug Dictionary](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/pyridoxal-phosphate)\n19. [Disorders affecting vitamin B6 metabolism, PubMed](https://pubmed.ncbi.nlm.nih.gov/30671974/)\n20. [Effectiveness of Pyridoxal-5′-Phosphate in PNPO Deficiency: A Systematic Review](https://pmc.ncbi.nlm.nih.gov/articles/PMC12317649/)\n21. [PLP-Dependent Enzymes, BioMed Research International special issue](https://onlinelibrary.wiley.com/doi/toc/10.1155/2738.si.536838)\n22. [A history of the isolation and identification of vitamin B6, USDA ARS](https://www.ars.usda.gov/research/publications/publication/?seqNo115=307845)\n\n---\n*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Metabolites, cofactors, and biomolecules › Coenzymes and cofactors › Vitamin-derived coenzymes › Pyridoxal phosphate*\n\n*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/pyridoxal-phosphate", "markdown_url": "https://www.edgepedia.org/pyridoxal-phosphate.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Pyridoxal phosphate\", Edgepedia (EdgeChat), https://www.edgepedia.org/pyridoxal-phosphate. Edgepedia Community License 1.0.", "credit_md": "\"[Pyridoxal phosphate](https://www.edgepedia.org/pyridoxal-phosphate)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/pyridoxal-phosphate](https://www.edgepedia.org/pyridoxal-phosphate). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Pyridoxal phosphate\", Edgepedia (EdgeChat), https://www.edgepedia.org/pyridoxal-phosphate. Edgepedia Community License 1.0.", "speakable": "Pyridoxal phosphate is the active coenzyme form of vitamin B6, serving over 140 EC-classified enzyme activities in transamination, decarboxylation, and related amino acid reactions via an external aldimine intermediate." }