BioPAX pathway converted from "Vitamins B6 activation to pyridoxal phosphate" in the Reactome database.

Vitamins B6 activation to pyridoxal phosphate

Animals cannot synthesize pyridoxal 5'-phosphate (PLP) which is a ligand in aminotransferases and other enzymes. PLP's accessible derivatives pyridoxine, pyridoxal, and pyridoxamine are traditionally called vitamins B6. They are taken up nutritionally from bacteria and plants, but also created from PLP in the body. The pathways used to recycle PLP from these three compounds can therefore be called vitamin B6 activation as well as PLP salvage. Because of the close similarity of the molecules, only two enzymes are needed for the task (McCormick & Chen, 1999).

Authored: Stephan, R, 2010-09-16Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

2.7.1.35

2xPDXK:2xZn2+ phosphorylates PXL

PLP results from phosphorylation of pyridoxalPyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxal (PXL) to form pyridoxal 5'-phosphate (PXLP) (Lee et al. 2000, di Salvo et al. 2004).

Authored: Stephan, R, 2010-09-16Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

Reactome DB_ID: 965131

cytosolGO0005829

pyridoxal [ChEBI:17310]

pyridoxal

Reactomehttp://www.reactome.orgChEBI17310

Reactome DB_ID: 113592

ATP(4-) [ChEBI:30616]

ATP(4-)

Adenosine 5'-triphosphateatpATP

ChEBI30616

Reactome DB_ID: 29390

pyridoxal 5'-phosphate [ChEBI:18405]

pyridoxal 5'-phosphate

ChEBI18405

Reactome DB_ID: 29370

ADP(3-) [ChEBI:456216]

ADP(3-)

ADP trianion5'-O-[(phosphonatooxy)phosphinato]adenosineADP

ChEBI456216PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 965005

2xPDXK:2xZn2+ [cytosol]

2xPDXK:2xZn2+

PDXK holoenzyme

Reactome DB_ID: 965175

UniProt:O00764 PDXK

PDXK

PDXKPRED79C21orf124C21orf97PKHPNKFUNCTION Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (PubMed:9099727, PubMed:10987144, PubMed:17766369, PubMed:19351586, PubMed:31187503) (Probable). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions.ACTIVITY REGULATION Catalytic activity is inhibited competitively by 4-deoxypyridoxine, and is also inhibited by the benzodiazepine receptor ligands 1012S and ethyl-beta-carboline-3-carboxylate (PubMed:9099727). Inhibited by ginkgotoxin, theophylline, lamotrigine, enprofylline, theobromine, and caffeine (PubMed:22879864). Activity is increased in the presence of K(+)or Na(+) (PubMed:17766369).PATHWAY Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal 5'-phosphate from pyridoxal: step 1/1.PATHWAY Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxine 5'-phosphate from pyridoxine: step 1/1.PATHWAY Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxamine 5'-phosphate from pyridoxamine: step 1/1.SUBUNIT Homodimer.TISSUE SPECIFICITY Ubiquitous (PubMed:9099727, PubMed:31187503). Highly expressed in testis (PubMed:9099727).INDUCTION Transcriptionally regulated by Sp1 transcription factor.SIMILARITY Belongs to the pyridoxine kinase family.

Homo sapiens

NCBI Taxonomy9606UniProtO00764

Chain Coordinates

EQUAL

312

EQUAL

Reactome DB_ID: 29426

zinc(2+) [ChEBI:29105]

zinc(2+)

ChEBI29105Reactome Database ID Release 75965005Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=965005ReactomeR-HSA-965005

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-965005.1GO0008478

GO molecular function

Reactome Database ID Release 75965111Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=965111Reactome Database ID Release 75964970Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964970ReactomeR-HSA-964970

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964970.110987144Pubmed2000Human pyridoxal kinase: overexpression and properties of the recombinant enzymeLee, HSMoon, BJChoi, SYKwon, OSMol Cells 10:452-915249053Pubmed2004Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinasesdi Salvo, MLHunt, SSchirch, VProtein Expr Purif 36:300-6

2.7.1.35

2xPDXK:2xZn2+ phosphorylates PXA

Pyridoxamine is phosphorylatedPyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxamine (PXA) to form pyridoxamine phosphate (PXAP) (Lee et al. 2000, di Salvo et al. 2004).

Authored: Stephan, R, 2010-09-16Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

Reactome DB_ID: 964945

pyridoxamine [ChEBI:16410]

pyridoxamine

ChEBI16410

Reactome DB_ID: 113592

Reactome DB_ID: 965146

pyridoxamine 5'-phosphate [ChEBI:18335]

pyridoxamine 5'-phosphate

ChEBI18335

Reactome DB_ID: 29370

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 965005

Reactome Database ID Release 75964958Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964958ReactomeR-HSA-964958

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964958.1

2.7.1.35

2xPDKX:2xZn2+ phosphorylates PDX

Pyridoxine is phosphorylatedPyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxine (PDX) to form pyridoxine phosphate (PDXP) (Lee et al. 2000, di Salvo et al. 2004).

Authored: Stephan, R, 2010-09-16Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

Reactome DB_ID: 965053

pyridoxine [ChEBI:16709]

pyridoxine

ChEBI16709

Reactome DB_ID: 113592

Reactome DB_ID: 964952

pyridoxine 5'-phosphate [ChEBI:28803]

pyridoxine 5'-phosphate

ChEBI28803

Reactome DB_ID: 29370

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 965005

Reactome Database ID Release 75964962Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964962ReactomeR-HSA-964962

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964962.1

1.4.3.5

2xPNPO:2xFMN oxidizes PXAP to PXLP

PLP from oxidation of pyridoxamine phosphatePyridoxine-5'-phosphate oxidase (PNPO) is able to oxidize pyridoxamine phosphate (PXAP) to pyridoxal 5'-phosphate (PXLP) (Kang et al. 2004).

Authored: Stephan, R, 2010-09-18Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

Reactome DB_ID: 965146

Reactome DB_ID: 29368

dioxygen [ChEBI:15379]

dioxygen

ChEBI15379

Reactome DB_ID: 29356

water [ChEBI:15377]

water

ChEBI15377

Reactome DB_ID: 29390

Reactome DB_ID: 31633

ammonium [ChEBI:28938]

ammonium

ChEBI28938

Reactome DB_ID: 29408

hydrogen peroxide [ChEBI:16240]

hydrogen peroxide

ChEBI16240PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 964943

2xPNPO:2xFMN [cytosol]

2xPNPO:2xFMN

PNPO holoenzyme

Reactome DB_ID: 965023

UniProt:Q9NVS9 PNPO

PNPO

PNPOFUNCTION Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).PATHWAY Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal 5'-phosphate from pyridoxamine 5'-phosphate: step 1/1.PATHWAY Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal 5'-phosphate from pyridoxine 5'-phosphate: step 1/1.SUBUNIT Homodimer.SIMILARITY Belongs to the pyridoxamine 5'-phosphate oxidase family.

UniProtQ9NVS9

EQUAL

261

EQUAL

Reactome DB_ID: 73524

FMN [ChEBI:17621]

FMN

Flavin mononucleotideRiboflavin-5-phosphate

ChEBI17621Reactome Database ID Release 75964943Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964943ReactomeR-HSA-964943

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964943.1GO0004733

GO molecular function

Reactome Database ID Release 75965270Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=965270Reactome Database ID Release 75965079Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=965079ReactomeR-HSA-965079

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-965079.115182361Pubmed2004Genomic organization, tissue distribution and deletion mutation of human pyridoxine 5'-phosphate oxidaseKang, JHHong, MLKim, DWPark, JKang, TCWon, MHBaek, NIMoon, BJChoi, SYKwon, OSEur J Biochem 271:2452-61

1.4.3.5

2xPNPO:2xFMN oxidizes PDXP to PXLP

PLP from oxidation of pyridoxine phosphatePyridoxine-5'-phosphate oxidase (PNPO) is able to oxidize pyridoxine phosphate (PDXP) to pyridoxal 5'-phosphate (PXLP) (Kang et al. 2004).

Authored: Stephan, R, 2010-09-18Reviewed: D'Eustachio, P, 2010-11-08Edited: Jassal, B, 2010-09-20

Reactome DB_ID: 29368

Reactome DB_ID: 964952

Reactome DB_ID: 29390

Reactome DB_ID: 29408

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 964943

Reactome Database ID Release 75965019Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=965019ReactomeR-HSA-965019

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-965019.1

1.2.3.1

AOX1 oxidises PXL to PDXate

Aldehyde oxidase (AOX1) is a complex molybdo-flavoprotein that belongs to the xanthine oxidase family. It is active as a homodimer, with each monomer binding two distinct [2Fe2S] clusters, FAD and the molybdenum cofactor. AOX1 plays an important role in the metabolism of drugs based on its broad substrate specificity oxidising aromatic aza-heterocycles and aldehydes (Hartmann et al. 2012).

Authored: Jassal, Bijay, 2013-03-01Reviewed: D'Eustachio, P, 2013-04-15Edited: Jassal, Bijay, 2013-03-01

Reactome DB_ID: 965131

Reactome DB_ID: 29368

Reactome DB_ID: 29356

Reactome DB_ID: 3204324

4-pyridoxic acid [ChEBI:17405]

4-pyridoxic acid

ChEBI17405

Reactome DB_ID: 29408

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 3204316

2xAOX1:cofactors [cytosol]

2xAOX1:cofactors

AOX1 dimer:2x2Fe-2S:FAD:MPT

Reactome DB_ID: 3204315

AOX1:cofactors [cytosol]

AOX1:cofactors

AOX1:2x2Fe-2S:FAD:MPT

Reactome DB_ID: 937126

tetra-mu3-sulfido-tetrairon(2+) [ChEBI:33722]

tetra-mu3-sulfido-tetrairon(2+)

ChEBI33722

Reactome DB_ID: 29386

FAD [ChEBI:16238]

FAD

Flavin adenine dinucleotide

ChEBI16238

Reactome DB_ID: 38025

molybdopterin [ChEBI:44074]

molybdopterin

ChEBI44074

Reactome DB_ID: 3204326

UniProt:Q06278 AOX1

AOX1

AOX1AOFUNCTION Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.ACTIVITY REGULATION Is very potently inhibited by raloxifene (PubMed:26842593). Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, isovanillin and thioridazine. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:9224775, PubMed:26322824).SUBUNIT Homodimer.TISSUE SPECIFICITY Abundant in liver, expressed in adipose tissue and at lower levels in lung, skeletal muscle, pancreas. In contrast to mice, no significant gender difference in AOX1 expression level (at protein level).DEVELOPMENTAL STAGE Not detected in preadipocytes but strongly induced in mature adipocytes.INDUCTION In liver, is down-regulated by adiponectin and by the PPARA agonist, fenofibric acid.MISCELLANEOUS AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:22335465).SIMILARITY Belongs to the xanthine dehydrogenase family.CAUTION Was originally thought to be a xanthine dehydrogenase.

UniProtQ06278

EQUAL

1338

EQUAL

Reactome Database ID Release 753204315Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3204315ReactomeR-HSA-3204315

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3204315.1Reactome Database ID Release 753204316Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3204316ReactomeR-HSA-3204316

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3204316.1GO0004031

GO molecular function

Reactome Database ID Release 753204329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3204329Reactome Database ID Release 753204311Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3204311ReactomeR-HSA-3204311

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3204311.122279051Pubmed2012The impact of single nucleotide polymorphisms on human aldehyde oxidaseHartmann, TobiasTerao, MinekoGarattini, EnricoTeutloff, ChristianAlfaro, Joshua FJones, Jeffrey PLeimkühler, SilkeDrug Metab. Dispos. 40:856-64

Reactome Database ID Release 75964975Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964975ReactomeR-HSA-964975

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964975.110024608Pubmed1999Update on interconversions of vitamin B-6 with its coenzymeMcCormick, DBChen, HJ Nutr 129:325-7GO0042816

GO biological process