Editing Pyridoxal phosphate (section)

== Absorption and Transport ==
{{Main|Vitamin B6}}

In normal conditions, the human intestine absorbs maily nonphosphorylated B6 vitamers. The phosphorylated forms of B6 and the glucoside of pyridoxine can be hydrolyzed by intestinal phosphatases and an intestinal glycosidase, respectively, to promote passive diffusion of pyridoxamine, pyridoxine and pyridoxal. In the liver or intestine, they are then rephosphorylated by pyridoxal kinase (EC 2.7.1.35) to avoid inverse diffusion <ref name="pmid30671974">{{cite journal | vauthors = Wilson MP, Plecko B, Mills PB, Clayton PT | title = Disorders affecting vitamin B6 metabolism | journal = J Inherit Metab Dis | volume = 42 | issue = 4 | pages = 629–646 | pmid = 30671974 | pmc = 2242600 | doi = 10.1002/jimd.12060 }}</ref> 
A [[transport protein]] / membrane carrier of PLP (and other phosphorylated forms of B6) is the human membrane enzyme NAPE-PLD [[N-acyl phosphatidylethanolamine-specific phospholipase D]] of the [[endocannabinoid system]].<ref name="pmid39999832">{{cite journal | vauthors = Chiarugi S, Margheriti F, De Lorenzi V, Martino E, Margheritis EG, Moscardini A, Marotta R, Chaves-Sanjuan A, Del Seppia C, Federighi G, Lapi D, Bandiera T, Rapposelli S, Scuri R, Bolognesi M, Garau G | title = NAPE-PLD is target of thiazide diuretics | journal = Cell Chem Biol  | volume = 32 | issue = 3 | pages = 449–462 | pmid = 39999832 | doi = 10.1016/j.chembiol.2025.01.008 }}</ref> In the presence of [[bile acids]] (e.g., [[digestion]]), NAPE-PLD with its internal channel creates membrane-pores as dynamic conductive pathways through which the charged cofactors of vitamin B6 can diffuse through cell membranes and membranes of subcellular compartments (e.g., mitochondria, peroxisome, and endosome), where they exert the specific enzymatic activities. NAPE-PLD is thus functional to the intracellular uptake and mobilization of PLP, and to the increased demand of the cofactor in pathological conditions having an higher endocannabinoid tone. Intracellular-free PLP concentrations are maintained at approximately 1 μM to prevent inappropriate reactions. Proteins that bind PLP and help maintain low-free PLP concentrations include glycogen phosphorylase in muscle, hemoglobin in erythrocytes, albumin in plasma, and NAPE-PLD mainly in the brain, gut, liver, kidney and reproductive system. When B6 vitamers intake exceeds requirements, PLP is dephosphorylated (mainly in the liver) and the pyridoxal is oxidized to pyridoxic acid prior to excretion in urine.