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DOI: 10.1055/s-0029-1185482
© Georg Thieme Verlag KG Stuttgart · New York
Influence of Antivitamins Ginkgotoxin 5′-Phosphate and Deoxypyridoxine 5′-Phosphate on Human Pyridoxine 5′-Phosphate Oxidase[*]
Publication History
received Dec. 18, 2008
revised January 28, 2009
accepted February 12, 2009
Publication Date:
13 March 2009 (online)
Abstract
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 B6 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 B6 vitamers, an interaction of ginkgotoxin with enzymes involved in the vitamin B6-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 B6 derivative 4′-deoxypyridoxine 5′-phosphate but not by ginkgotoxin or its 5′-phosphate.
Key words
Ginkgo biloba - Ginkgoaceae - ginkgotoxin 5′‐phosphate - 4′‐deoxypyridoxine 5′‐phosphate - pyridoxine 5′‐phosphate oxidase - pyridoxal 5′‐phosphate phosphatase - vitamin B6
1 Dedicated to Dr. Heinz G. Floss on the occasion of his 75th birthday.
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1 Dedicated to Dr. Heinz G. Floss on the occasion of his 75th birthday.
Dr. C. Drewke
Institute of Pharmaceutical Biology
University of Bonn
Nussallee 6
53115 Bonn
Germany
Phone: + 49 2 28 73 25 63
Fax: + 49 2 28 73 32 50
Email: cdrewke@uni-bonn.de