Influence of antivitamins ginkgotoxin 5'-phosphate and deoxypyridoxine 5'-phosphate on human pyridoxine 5'-phosphate oxidase.
The pharmacological effects of leaf extracts (EGb 761) from Ginkgo biloba L. are attributed to ginkgolides, bilobalide and biflavonoids. However, besides these beneficial attributes, ginkgotoxin, a B(6) antivitamin which may cause epileptic convulsions, other severe neuronal disorders and even death, is also found in Ginkgo leaves and leaf-derived remedies. Because of its structural similarity to the B(6) vitamers, an interaction of ginkgotoxin with enzymes involved in the vitamin B(6)-dependent metabolism of the human brain is possible. This led us to investigate how the neurotoxic ginkgotoxin acts in the brain. To this end the gene coding for the human pyridoxine 5'-phosphate oxidase was heterologously overexpressed in E. COLI and the homogeneous enzyme was characterized. The investigation showed that the enzyme is inhibited in vitro by the synthetic vitamin B(6) derivative 4'-deoxypyridoxine 5'-phosphate but not by ginkgotoxin or its 5'-phosphate.
Salamon
Nora
N
Institute of Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany.
Gurgui
Cristian
C
Leistner
Eckhard
E
Drewke
Christel
C
D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011734:Pyridoxaminephosphate Oxidase / Q000302:isolation & purification / Q000378:metabolism*; D025101:Vitamin B 6 / Q000037:antagonists & inhibitors*; D000096983:Ginkgo Extract
D010936:Plant Extracts; D011732:Pyridoxal Phosphate; D011734:Pyridoxaminephosphate Oxidase; D025101:Vitamin B 6; C435936:4'-O-methylpyridoxine-5'-phosphate; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C002064:4-deoxypyridoxine 5'-phosphate