Ginkgotoxin
Encyclopedia
Ginkgotoxin is a neurotoxin
naturally occurring in Ginkgo biloba. It is an antivitamin structurally related to vitamin B6
(pyridoxine). It has the capacity to induce epileptic seizures.
, and to treat neuronal disorders. It has been long used for a wide range of medicinal purposes. For instance, in Japan
and China
, Ginkgo biloba is used to treat cough
, bronchial asthma, irritable bladder
and alcohol abuse
.
Ginkgotoxin is found in the seeds and, in lesser amounts, in the leaves of Gingko biloba. The seeds can be consumed as is and the leaves can be used to prepare the dietary supplements. Analyses of raw seeds from eight different location in Japan by high-performance liquid chromatography
showed concentrations of ginkgotoxin varying from 0.173 to 0.4mg/g of seeds. Also, there is a seasonal variation of ginkgotoxin concentration in the seeds. The maximum has been observed in August. Analyses of the powder of Ginkgo biloba capsules revealed the presence of ginkgotoxin. However, as the leaves contain very small amounts that are not of toxicological relevance, it shouldn't pose any threat to the consumers.
Ginkgotoxin-5'-glucoside is a derivative of ginkgotoxin that possesses a glycosyl
in the 5' position. Its content is higher than the concentration of ginkgotoxin in heated seeds (boiled or roasted). Liberation of ginkgotoxin by enzymatic hydrolysis
of the glycosidic linkage is possible. Nevertheless, the toxicity
of the mechanism of action glucoside form is not fully understood.
Ginkgotoxin can also be found in other plants of the genus Albizia
. However, these plants have no known dietary use for humans, so their production of ginkgotoxin is of lesser concern.
), but the presence of the vitamin is not required for the biosynthesis
of ginkgotoxin. It indicates that the pyridoxine system can be synthesized de novo
in the cells of Ginkgo biloba. The first step of the biosynthesis involves ribulose 5-phosphate
and dihydroxyacetone phosphate. They react in the presence of a synthase
complex consisting of Pdx1
and Pdx2, and form pyridoxal phosphate. The second step is hypothetical and consists of the removal of a hydride
in the presence of a dehydrogenase
to produce pyridoxine. The last step involves the O-methylation of pyridoxine to form 4'-O-methylpyridoxine (ginkgotoxin).
Ginkgotoxin is structurally related to vitamin B6. It is suggested that ginkgotoxin interferes with the synthesis of the vitamin by decreasing the activity of pyridoxal kinase
in mammals. This decrease leads to the decreased availability of glutamate decarboxylase
. In turn, it causes an imbalance between excitation and inhibition of neurotransmitters. This results in epileptic seizures. The toxicity of ginkgotoxin can consequently be relieved by taking vitamin B6 supplements.
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
naturally occurring in Ginkgo biloba. It is an antivitamin structurally related to vitamin B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
(pyridoxine). It has the capacity to induce epileptic seizures.
Occurrence
Seeds and phytopharmaceutics derived from the plant Ginkgo biloba are dietary supplements used to improve memory, brain metabolism, and blood flowBlood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
, and to treat neuronal disorders. It has been long used for a wide range of medicinal purposes. For instance, in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
and China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, Ginkgo biloba is used to treat cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, bronchial asthma, irritable bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
and alcohol abuse
Alcohol abuse
Alcohol abuse, as described in the DSM-IV, is a psychiatric diagnosis describing the recurring use of alcoholic beverages despite negative consequences. Alcohol abuse eventually progresses to alcoholism, a condition in which an individual becomes dependent on alcoholic beverages in order to avoid...
.
Ginkgotoxin is found in the seeds and, in lesser amounts, in the leaves of Gingko biloba. The seeds can be consumed as is and the leaves can be used to prepare the dietary supplements. Analyses of raw seeds from eight different location in Japan by high-performance liquid chromatography
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
showed concentrations of ginkgotoxin varying from 0.173 to 0.4mg/g of seeds. Also, there is a seasonal variation of ginkgotoxin concentration in the seeds. The maximum has been observed in August. Analyses of the powder of Ginkgo biloba capsules revealed the presence of ginkgotoxin. However, as the leaves contain very small amounts that are not of toxicological relevance, it shouldn't pose any threat to the consumers.
Ginkgotoxin-5'-glucoside is a derivative of ginkgotoxin that possesses a glycosyl
Glycosyl
A glycosyl group is a univalent free radical or substituent structure obtained by removing the hemiacetal hydroxyl group from the cyclic form of a monosaccharide and, by extension, of a lower oligosaccharide....
in the 5' position. Its content is higher than the concentration of ginkgotoxin in heated seeds (boiled or roasted). Liberation of ginkgotoxin by enzymatic hydrolysis
Enzymatic hydrolysis
Enzymatic hydrolysis is a process in digestion in which macromolecules are split from food by the enzymatic addition of water.It may be used to help provide renewable energy, as with Cellulosic ethanol....
of the glycosidic linkage is possible. Nevertheless, the toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
of the mechanism of action glucoside form is not fully understood.
Ginkgotoxin can also be found in other plants of the genus Albizia
Albizia
Albizia is a genus of about 150 species of mostly fast-growing subtropical and tropical trees and shrubs in the subfamily Mimosoideae of the legume family, Fabaceae. The genus is pantropical, occurring in Asia, Africa, Madagascar, Central, South, and southern North America and Australia, but mostly...
. However, these plants have no known dietary use for humans, so their production of ginkgotoxin is of lesser concern.
Biosynthesis
Ginkgotoxin is the 4'-O-methyl derivative of vitamin B6 (pyridoxinePyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
), but the presence of the vitamin is not required for the biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of ginkgotoxin. It indicates that the pyridoxine system can be synthesized de novo
De novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
in the cells of Ginkgo biloba. The first step of the biosynthesis involves ribulose 5-phosphate
Ribulose 5-phosphate
Ribulose 5-phosphate is one of the end-products of the pentose phosphate pathway. It is also an intermediate in the Calvin cycle.It is formed by phosphogluconate dehydrogenase, and it can be acted upon by phosphopentose isomerase and phosphopentose epimerase....
and dihydroxyacetone phosphate. They react in the presence of a synthase
Synthase
In biochemistry, a synthase is an enzyme that catalyses a synthesis process.Following the EC number classification, they belong to the group of ligases, with lyases catalysing the reverse reaction....
complex consisting of Pdx1
Pdx1
Pdx1 , also known as insulin promoter factor 1, is a transcription factor necessary for pancreatic development and β-cell maturation...
and Pdx2, and form pyridoxal phosphate. The second step is hypothetical and consists of the removal of a hydride
Hydride
In chemistry, a hydride is the anion of hydrogen, H−, or, more commonly, a compound in which one or more hydrogen centres have nucleophilic, reducing, or basic properties. In compounds that are regarded as hydrides, hydrogen is bonded to a more electropositive element or group...
in the presence of a dehydrogenase
Dehydrogenase
A dehydrogenase is an enzyme that oxidises a substrate by a reduction reaction that transfers one or more hydrides to an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN.-Examples:...
to produce pyridoxine. The last step involves the O-methylation of pyridoxine to form 4'-O-methylpyridoxine (ginkgotoxin).
Toxicity
A few cases reported poisoning from commercially available products. The consumption of seeds represent a greater concern. Indeed, overconsumption of Ginkgo biloba seeds, especially by children, can result in loss of consciousness, convulsions and even death.Ginkgotoxin is structurally related to vitamin B6. It is suggested that ginkgotoxin interferes with the synthesis of the vitamin by decreasing the activity of pyridoxal kinase
Pyridoxal kinase
In enzymology, a pyridoxal kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and pyridoxal, whereas its two products are ADP and pyridoxal 5'-phosphate....
in mammals. This decrease leads to the decreased availability of glutamate decarboxylase
Glutamate decarboxylase
Glutamate decarboxylase or glutamic acid decarboxylase is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor. The reaction proceeds as follows:...
. In turn, it causes an imbalance between excitation and inhibition of neurotransmitters. This results in epileptic seizures. The toxicity of ginkgotoxin can consequently be relieved by taking vitamin B6 supplements.