The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba.
Ginkgotoxin (4'-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B(6). Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B(6) antivitamins including ginkgotoxin on recombinant homogeneous human pyridoxal kinase (EC 2.7.1.35). It is shown that ginkgotoxin serves as an alternate substrate for this enzyme with a lower K(m) value than pyridoxal, pyridoxamine or pyridoxine. Thus, the presence of ginkgotoxin leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly also in vivo. Our observations are discussed in light of Ginkgo medications used as nootropics.
Kästner
Uta
U
Institut für Pharmazeutische Biologie, Universität Bonn, Germany.
Hallmen
Christian
C
Wiese
Michael
M
Leistner
Eckhard
E
Drewke
Christel
C
D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011731:Pyridoxal Kinase / Q000302:isolation & purification / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000378:metabolism; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013997:Time Factors; D025101:Vitamin B 6 / Q000737:chemistry / Q000378:metabolism; D014803:Vitamin B Complex / Q000737:chemistry / Q000378:metabolism
C406624:4'-O-methylpyridoxine; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D014803:Vitamin B Complex; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D011731:Pyridoxal Kinase; D011736:Pyridoxine