Vitamin B6-dependent and responsive disorders (Homo sapiens)

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1TNSALPPyridoxine dependentepilepsy (PDE)DietLysine degradation pathwayFig. 11.2PNPO2-keto 6-aminocaproic acidL-lysineALPLIPP5C dehydrogenasepyridoxalPipecolic acidP5CPLPpyridoxamine-pPyridoxal-PAntiquitinPLPpiperideine-2-carboxylateVitamin B6pyridoxalglutamic semialdehydeSaccharopinePIGV anchorpyridoxamine-pL-prolinePyridoxine-PpyridoxaminePyridoxal-Pglutamic acidalpha aminoadipic semialdehydepyridoxaminepyridoxamine-palpha aminoadipic acidPyridoxinepyridoxine-glucosidePyridoxine-PPyridoxineP6CCatabolism of L-prolineFig. 11.3PKPKAbsorptionIPPKHepatic metabolismBloodCell membraneLEGEND:Release into circulation (transport out of liver)Cellular uptake or transport accross blood-brain barrierBlood-brain barrier(Brain) cellPKPKPKPNPOVitamine B6 metabolismFig. 11.1Hyperprolinaemia type IIPNPO deficiencyPNPO deficiencyCongential hypophosphatasia


Vitamine B6 is absorbed in different vitamers, which undergo several (de)phosphorylation steps, to be able to pas the blood-brain barrier. Within the brain, PLP (Pyridoxal-P) is the only active cofactor for intracellular enzyme reactions. PLP catalyses over 100 reactions, mainly related to amino acids and neurotransmitter metabolism. Bold lines in the Figure show how the major source of PLP is divided in the body.

A number of genetic defects have been identified as the underlying cause of vitamine B6 dependent epilepsies, particularly occurring in the neonatal life stage, which could lead to irreversible brain damage or could be fatal. The disorders related to this pathway can be divided in two categories: reduced production/availability of PLP or inactivation of PLP by formation of Knoevenagel products. Specific biomarkers from urine, plasma or Cerebral Spinal Fluid (CSF) exist to distinguish the disorders. Oral treatment with PL or PLP is available, as well as intrauterine treatment with vitamine B6 for mothers in the early stages of pregnancy.

This pathway was inspired by Chapter 11 of the book of Blau (ISBN 3642403360 (978-3642403361)).

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  1. Blau, N., Duran, M., Gibson, K.M., Dionisi-Vici, C.; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Chapter 11''; SBN 978-3-642-40337-8, 2014


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110710view14:41, 28 May 2020Marvin M2changed unknown node to geneproduct
109214view15:28, 27 February 2020SusanChanged annotation type
109213view15:26, 27 February 2020SusanAdded annotation to PNPO
108081view11:49, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
104423view15:00, 24 May 2019EgonwRemoved
104396view14:18, 23 May 2019Mkutmonadded one Rhea identifier
104023view17:38, 25 April 2019IreneHemelModified description
102316view13:47, 19 December 2018DeSlChanged wrong ID for glutamic semialdehyde
98922view05:18, 16 October 2018EgonwModified description
98254view09:48, 15 August 2018DeSlModified description
98252view09:45, 15 August 2018DeSlChanged disease nodes to labels, changed layout of background colour slighlty.
97294view20:25, 7 May 2018Khanspersconnected interactions
96743view06:05, 2 April 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96735view15:03, 1 April 2018EgonwConverted interactions to regular arrows, which were not mim:conversions.
96671view15:26, 25 March 2018EgonwConverted interactions to regular arrows, which were not mim:conversions.
96570view13:23, 20 March 2018Lisaaheldadded more ID's
96569view13:08, 20 March 2018LisaaheldAdded ID's
96568view12:54, 20 March 2018LisaaheldAdded IDs
96534view21:07, 17 March 2018DeSlConnected all unconnected lines
96513view16:16, 16 March 2018DeSlOntology Term : 'neural cell' added !
96512view16:13, 16 March 2018DeSlOntology Term : 'hyperprolinemia type II disease pathway' added !
96511view16:12, 16 March 2018DeSlOntology Term : 'hypophosphatasia disease pathway' added !
96510view16:12, 16 March 2018DeSlOntology Term : 'infantile hypophosphatasia' added !
96509view16:12, 16 March 2018DeSlOntology Term : 'childhood hypophosphatasia' added !
96508view16:11, 16 March 2018DeSlOntology Term : 'hypophosphatasia' added !
96507view16:11, 16 March 2018DeSlOntology Term : 'lysine degradation pathway' added !
96506view16:10, 16 March 2018DeSlOntology Term : 'vitamin B6 metabolic pathway' added !
96505view16:08, 16 March 2018DeSladded last 2 diseases, changed layout a bit more.
96504view15:38, 16 March 2018DeSlModified description
96503view15:37, 16 March 2018DeSlAdded OMIM IDs for diseases, removed BIND IDs for conversions which were not needed.
96502view15:35, 16 March 2018DeSlModified description
96501view15:25, 16 March 2018DeSlMade various layout changes, added more metabolites+enzymes, changed wrong IDs
96486view16:45, 15 March 2018LisaaheldAddes ASA
96475view16:06, 15 March 2018Lisaaheldmade P5C and P6C red and gave name
96292view15:50, 7 March 2018LisaaheldNew pathway

External references


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NameTypeDatabase referenceComment
2-keto 6-aminocaproic acidMetaboliteCHEBI:17534 (ChEBI)
ALPLProteinEnsembl:ENSG00000162551 (Ensembl) Alkaline phosphatase
AntiquitinProteinENSG00000164904 (Ensembl) Aldehyde dehydrogenase 7 family, member A1, also known as ALDH7A1 or antiquitin
IPPathwayENSG00000163295 (Ensembl) Intestinal alkaline phosphatases
L-lysineMetaboliteCHEBI:18019 (ChEBI)
L-prolineMetaboliteCHEBI:17203 (ChEBI)
P5C dehydrogenaseProteinIPR005931 (InterPro)
P5CMetaboliteCHEBI:17388 (ChEBI) delta1-pyrroline-5-carboxylate (P5C)
P6CMetaboliteCHEBI:16987 (ChEBI) piperideine-6-carboxylate
PIGV anchorProteinENSG00000060642 (Ensembl)
PKProteinPhosphate kinase
PLPMetaboliteCHEBI:18405 (ChEBI) Pyridoxal-5-Phosphate (=PLP)
PNPOProteinENSG00000108439 (Ensembl) pyridoxamine 5'-phosphate oxidase
Pipecolic acidMetaboliteCHEBI:30913 (ChEBI)
Pyridoxal-PMetaboliteCHEBI:18405 (ChEBI)
Pyridoxine-PMetaboliteCHEBI:28803 (ChEBI)
PyridoxineMetaboliteCHEBI:16709 (ChEBI)
SaccharopineMetaboliteCHEBI:16927 (ChEBI)
Vitamin B6MetaboliteCHEBI:27306 (ChEBI)
alpha aminoadipic acidMetaboliteCHEBI:37024 (ChEBI)
alpha aminoadipic semialdehydeProteinENSG00000008311 (Ensembl)
glutamic acidMetaboliteCHEBI:29985 (ChEBI)
glutamic semialdehydeMetaboliteCHEBI:58066 (ChEBI) Drawing in Chapter 11 Blau contains an error for this metabolite, one carbon is missing from the structure!
piperideine-2-carboxylateMetaboliteCHEBI:16187 (ChEBI)
pyridoxalMetaboliteCHEBI:17310 (ChEBI) AKA PL
pyridoxamine-pMetaboliteCHEBI:18335 (ChEBI)
pyridoxamineMetaboliteCHEBI:57761 (ChEBI)
pyridoxine-glucosideMetaboliteCHEBI:17382 (ChEBI) pyridoxine-5'-beta-D-glucoside aka PNG aka pyridoxine-glucoside

Annotated Interactions

SourceTargetTypeDatabase referenceComment
glutamic semialdehydeglutamic acidmim-conversion30236 (Rhea) P5C dehydrogenase
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