Ginkgotoxin

Abstract: 4'-O-methylpyridoxine (ginkgotoxin) is a neurotoxic antivitamin B6 which occurs in Ginkgo biloba L. seeds. Contrary to a previous report by Wada et al., the toxin was also detected in Ginkgo biloba leaves. The leaves are a source of extracts (e.g. EGb761) employed in the preparation of Ginkgo medications. Consequently the toxin is also present in Ginkgo medications and is even detectable in homoeopathic preparations. The toxin occurs also in boiled Japanese Ginkgo food. However, the amount of the toxin is likely to be too low to exert a detrimental effect after administration of the medication or ingestion of food.

Abstract: In spite of the rather simple structure of pyridoxal 5'-phosphate (I), a member of the vitamin B6 group, the elucidation of its de novo biosynthesis remained largely unexplored until recently. Experiments designed to investigate the formation of the vitamin B6 pyridine nucleus mainly concentrated on Escherichia coli. The results of tracer experiments with radioactive and stable isotopes, feeding experiments, and molecular biological studies led to the prediction that 4-hydroxy-L-threonine (VIII, R = H) and 1-deoxy-D-xylulose (VII, R = H) are precursors which are assembled to yield the carbon-nitrogen skeleton of vitamin B6. At this point, the involvement of the phosphorylated forms of these precursors in this assembly seems quite clear. However, vitamin B6 biosynthesis in organisms other than E. coli remains largely unknown. Toxic derivatives of vitamin B6, such as ginkgotoxin, occurring in higher plants may be suitable targets to gain further insight into this tricky problem.

Abstract: An antivitamin B6, 4'-methoxypyridoxine (1) was isolated from the seed of Ginkgo biloba L. (Ginkgoaceae). The albumen of the seed of G. biloba L., which is called "Gin-nan or Ginkyo", is used as a crude drug in China and as food in Japan. However, in Japan, there have been about 70 reports of "Gin-nan sitotoxism." In this paper, we report that the substance responsible for this sitotoxism is 4'-methoxypyridoxine (1), which is known to have antivitamin B6 activities. This compound (1) is reported for the first time from natural products.

Abstract: Ginkgotoxin (4′-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B6. Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B6 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 Km 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.