Vitamin B6-dependent and responsive disorders (Homo sapiens)

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1TNSALPDietLysine degradation pathwayFig. 11.2PNPO2-keto 6-aminocaproic acidL-lysineALPLIPP5C dehydrogenasepyridoxalPipecolic acidP5CPLPpyridoxamine-pPyridoxal-PAntiquitinPLPpiperideine-2-carboxylateVitamin B6pyridoxalglutamic semialdehydeSaccharopinePIGV anchorpyridoxamine-pL-prolinePyridoxine-PpyridoxaminePyridoxal-Pglutamic acidalpha aminoadipic semialdehydepyridoxamineHyperprolinaemia type IIpyridoxamine-palpha aminoadipic acidPyridoxinepyridoxine-glucosidePyridoxine-PPyridoxineP6CPyridoxine dependentepilepsy (PDE)Catabolism 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) cellPKPKPKPNPOPNPO deficiencyPNPO deficiencyCongential hypophosphatasiaVitamine B6 metabolismFig. 11.1


Description

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.

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Ontology Terms

 

Bibliography

  1. Anja Fux, Stephan A Sieber; ''Biochemical and Proteomic Studies of Human Pyridoxal 5′-Phosphate-Binding Protein (PLPBP)''; ACS Chem Biol ., 2020 PubMed Europe PMC Scholia
  2. Peter T Clayton; ''B6-responsive disorders: a model of vitamin dependency''; J Inherit Metab Dis ., 2006 PubMed Europe PMC Scholia
  3. 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

History

View all...
CompareRevisionActionTimeUserComment
128520view01:20, 11 February 2024EweitzModified description
128519view01:16, 11 February 2024EweitzFix typos, refine legend, soften disease color, standardize case
126057view13:43, 31 March 2023DeSlConnected unconnected line
126056view13:42, 31 March 2023DeSlChanged IP to Protein iso PW node
124956view08:30, 7 January 2023EgonwFixed the OMIM link patterns
124218view08:23, 1 October 2022EgonwFixed a metabolite identifier: not a protein
124212view19:48, 29 September 2022EgonwFixed a small typo
124202view07:50, 29 September 2022DeSlConverted interactions to diseases to graphical lines
123788view14:34, 12 August 2022DeSlOntology Term : 'proline metabolic pathway' added !
123787view14:34, 12 August 2022DeSlOntology Term : 'pyridoxine-dependent epilepsy' added !
123786view14:33, 12 August 2022DeSlOntology Term : 'hyperprolinemia type 2' added !
123785view14:33, 12 August 2022DeSlOntology Term : 'early-onset vitamin B6-dependent epilepsy' added !
123784view14:32, 12 August 2022DeSlOntology Term : 'epilepsy' added !
123782view14:31, 12 August 2022DeSlAdding details on PLPBP, linked to last missing disorder
123781view14:21, 12 August 2022DeSlUpdating htpps to https
123780view14:19, 12 August 2022DeSlOntology Term : 'pyridoxamine 5'-phosphate oxidase deficiency' added !
123779view14:17, 12 August 2022DeSlChanged UniProt to Rhea for interaction database
123778view14:17, 12 August 2022DeSlUpdated ALPL ensembl ID
123777view14:15, 12 August 2022DeSlAdded new litref.
123776view14:13, 12 August 2022DeSlUpdated figure descriptions
123775view14:11, 12 August 2022DeSlUpdated to reflect Ed.5
123774view14:09, 12 August 2022DeSlUpdated legend
123773view14:04, 12 August 2022DeSlConverted lines to graphical ones, if connected to textLabel
123772view13:59, 12 August 2022DeSlAdded ID for PK, added Rhea IDs for three reactions (to PLP)
119281view10:43, 23 June 2021FinterlyAdded ISBN for book citation
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 !

External references

DataNodes

View all...
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
Congential hypophosphatasia241500 (OMIM)
  • DISEASE with OMIM ID
  • Pyridox(am)ine 5'-phosphate oxidase deficiency
Hyperprolinaemia type II239510 (OMIM) DISEASE with OMIM ID
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)
PNPO deficiency610090 (OMIM)
  • DISEASE with OMIM ID
  • Pyridox(am)ine 5'-phosphate oxidase deficiency
PNPOENSG00000108439 (Ensembl) pyridoxamine 5'-phosphate oxidase
Pipecolic acidMetaboliteCHEBI:6284 (ChEBI)
Pyridoxal-PMetaboliteCHEBI:18405 (ChEBI)
Pyridoxine dependent epilepsy (PDE)266100 (OMIM)
  • DISEASE with OMIM ID
  • aka Alpha-amino adipic semialdehyde (AASA) dehydrogenase deficiency
Pyridoxine-PMetaboliteCHEBI:28803 (ChEBI)
PyridoxineMetaboliteCHEBI:8671 (ChEBI)
SaccharopineMetaboliteCHEBI:7406 (ChEBI)
Vitamin B6MetaboliteCHEBI:27306 (ChEBI)
alpha aminoadipic acidMetaboliteCHEBI:37024 (ChEBI)
alpha aminoadipic semialdehydeProteinENSG00000008311 (Ensembl)
glutamic acidMetaboliteCHEBI:16015 (ChEBI)
glutamic semialdehydeMetabolite4392 (PubChem-compound) 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

No annotated interactions

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