Vitamin B6-dependent and responsive disorders (WP4228)

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)).
last edited


Lisaaheld, DeSl, Egonw, Khanspers, IreneHemel, Mkutmon, Fehrhart, Susan, Marvin M2, and Finterly

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Homo sapiens


Diseases Inborn Errors of Metabolism (IEM) Pathways Rare Diseases


Disease Ontology: hypophosphatasia childhood hypophosphatasia infantile hypophosphatasia

Cell Type Ontology: neural cell

Pathway Ontology: lysine degradation pathway hyperprolinemia type II pathway hypophosphatasia pathway disease pathway vitamin B6 metabolic pathway


Label Type Compact Identifier
PNPO GeneProduct ensembl:ENSG00000108439
2-keto 6-aminocaproic acid Metabolite ChEBI
L-lysine Metabolite ChEBI
ALPL Protein Ensembl
IP Pathway Ensembl
P5C dehydrogenase Protein InterPro
pyridoxal Metabolite ChEBI
Pipecolic acid Metabolite ChEBI
P5C Metabolite ChEBI
PLP Metabolite ChEBI
pyridoxamine-p Metabolite ChEBI
Pyridoxal-P Metabolite ChEBI
Antiquitin Protein Ensembl
PLP Metabolite ChEBI
piperideine-2-carboxylate Metabolite ChEBI
Vitamin B6 Metabolite ChEBI
pyridoxal Metabolite ChEBI
glutamic semialdehyde Metabolite ChEBI
Saccharopine Metabolite ChEBI
PIGV anchor Protein Ensembl
pyridoxamine-p Metabolite ChEBI
L-proline Metabolite ChEBI
Pyridoxine-P Metabolite ChEBI
pyridoxamine Metabolite ChEBI
Pyridoxal-P Metabolite ChEBI
glutamic acid Metabolite ChEBI
alpha aminoadipic semialdehyde Protein Ensembl
pyridoxamine Metabolite ChEBI
pyridoxamine-p Metabolite ChEBI
alpha aminoadipic acid Metabolite ChEBI
Pyridoxine Metabolite ChEBI
pyridoxine-glucoside Metabolite ChEBI
Pyridoxine-P Metabolite chebi:28803
Pyridoxine Metabolite chebi:16709
P6C Metabolite chebi:16987
PK Protein None
PK Protein None
IP Pathway ensembl:ENSG00000163295
PK Protein None
PK Protein None
PK Protein None
PK Protein None
PNPO Protein ensembl:ENSG00000108439


  1. PubMed Europe PMC Scholia