Ginkgotoxin

Last updated
Ginkgotoxin
Ginkgotoxin.png
Ginkgotoxin 3D structure.png
Names
Preferred IUPAC name
5-(Hydroxymethyl)-4-(methoxymethyl)-2-methylpyridin-3-ol
Other names
4'-O-methylpyridoxine; 4-O-methylpyridoxine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
PubChem CID
  • InChI=1S/C9H13NO3/c1-6-9(12)8(5-13-2)7(4-11)3-10-6/h3,11-12H,4-5H2,1-2H3 Yes check.svgY
    Key: SVINQHQHARVZFF-UHFFFAOYSA-N Yes check.svgY
  • Oc1c(c(cnc1C)CO)COC
Properties
C9H13NO3
Molar mass 183.207 g·mol−1
Hazards
GHS labelling:
GHS-pictogram-skull.svg
Danger
H300, H330
P260, P264, P270, P271, P284, P301+P310, P304+P340, P310, P320, P321, P330, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Ginkgotoxin (4'-O-methylpyridoxine) 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.

Contents

Occurrence

Seeds and phytopharmaceuticals derived from the plant Ginkgo biloba are dietary supplements used to improve memory, brain metabolism, and blood flow, and to treat neuronal disorders.[ medical citation needed ] 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 use disorder. [1]

Ginkgotoxin is found in the seeds and, in lesser amounts, in the leaves of Ginkgo 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 0.4 mg/g of seeds. [2] Also, there is a seasonal variation of ginkgotoxin concentration in the seeds. The maximum has been observed in August. [3] 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). [4] 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 . [3] 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 (pyridoxine), 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. [5]

Biosynthesis of ginkgotoxin Biosynthesis of ginkgotoxin (english).svg
Biosynthesis of ginkgotoxin

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). [1]

Toxicity

A few cases reported poisoning from commercially available products. The consumption of seeds represent a greater concern. Overconsumption of Ginkgo biloba seeds, especially by children, can result in loss of consciousness, convulsions, and death. [4]

Ginkgotoxin is structurally related to vitamin B6. It is suspected that ginkgotoxin interferes with the synthesis of the vitamin by decreasing the activity of pyridoxal kinase in mammals. [6] This decrease leads to the decreased availability of glutamate decarboxylase. In turn, it causes an imbalance between excitation and inhibition of neurotransmitters, resulting in epileptic seizures. [6] The toxicity of ginkgotoxin consequently can be relieved by taking vitamin B6 supplements.

Related Research Articles

<span class="mw-page-title-main">Riboflavin</span> Vitamin and supplement

Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in energy metabolism, cellular respiration, and antibody production, as well as normal growth and development. The coenzymes are also required for the metabolism of niacin, vitamin B6, and folate. Riboflavin is prescribed to treat corneal thinning, and taken orally, may reduce the incidence of migraine headaches in adults.

Vitamin B<sub>6</sub> Class of chemically related vitamins

Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.

<i>Ginkgo biloba</i> Species of tree

Ginkgo biloba, commonly known as ginkgo or gingko, also known as the maidenhair tree, is a species of gymnosperm tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils very similar to the living species, belonging to the genus Ginkgo, extend back to the Middle Jurassic epoch approximately 170 million years ago. The tree was cultivated early in human history and remains commonly planted.

<span class="mw-page-title-main">Homocystinuria</span> Medical condition

Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.

<span class="mw-page-title-main">Pyridoxal phosphate</span> Active form of vitamin B6

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

<span class="mw-page-title-main">Bilobalide</span> Chemical compound

Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba.

<span class="mw-page-title-main">Ginkgolide</span> Biologically active terpenic lactone

Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba. They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate.

<span class="mw-page-title-main">Alkylresorcinol</span> Class of chemical compounds

Alkylresorcinols (ARs), also known as resorcinolic lipids, are amphiphilic phenolic lipids characterised by a non-polar odd-numbered alkyl side chain with up to 27 carbon atoms attached to a polar resorcinol (1,3-dihydroxybenzene) ring.

<span class="mw-page-title-main">Cyanidin</span> Anthocyanidin pigment in flowering plant petals and fruits

Cyanidin is a natural organic compound. It is a particular type of anthocyanidin. It is a pigment found in many red berries including grapes, bilberry, blackberry, blueberry, cherry, chokeberry, cranberry, elderberry, hawthorn, loganberry, açai berry and raspberry. It can also be found in other fruits such as apples and plums, and in red cabbage and red onion. It has a characteristic reddish-purple color, though this can change with pH; solutions of the compound are red at pH < 3, violet at pH 7-8, and blue at pH > 11. In certain fruits, the highest concentrations of cyanidin are found in the seeds and skin. Cyanidin has been found to be a potent sirtuin 6 (SIRT6) activator.

<span class="mw-page-title-main">Pyridoxine 5′-phosphate oxidase</span> Class of enzymes

Pyridoxine 5′-phosphate oxidase is an enzyme, encoded by the PNPO gene, that catalyzes several reactions in the vitamin B6 metabolism pathway. Pyridoxine 5′-phosphate oxidase catalyzes the final, rate-limiting step in vitamin B6 metabolism, the biosynthesis of pyridoxal 5′-phosphate, the biologically active form of vitamin B6 which acts as an essential cofactor. Pyridoxine 5′-phosphate oxidase is a member of the enzyme class oxidases, or more specifically, oxidoreductases. These enzymes catalyze a simultaneous oxidation-reduction reaction. The substrate oxidase enzymes is hydroxlyated by one oxygen atom of molecular oxygen. Concurrently, the other oxygen atom is reduced to water. Even though molecular oxygen is the electron acceptor in these enzymes' reactions, they are unique because oxygen does not appear in the oxidized product.

In enzymology, a 4-hydroxythreonine-4-phosphate dehydrogenase (EC 1.1.1.262) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Pyridoxine 5'-phosphate synthase</span> Class of enzymes

In enzymology, a pyridoxine 5'-phosphate synthase (EC 2.6.99.2) is an enzyme that catalyzes the chemical reaction

Vitamins occur in a variety of related forms known as vitamers. A vitamer of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.

<span class="mw-page-title-main">4-Deoxypyridoxine</span> Chemical compound

4-Deoxypyridoxine is a vitamin B6 antagonist. It may be toxic to developing embryos since it can have negative effects on collagen and elastin during development. The presence of this compound can produce vitamin B6 deficiency, which suppresses the immune system. 4-Deoxypyridoxine lowers vitamin B6 concentration by competitively inhibiting some of the enzymes necessary for the regeneration of vitamin B6.The related immunosuppression can be beneficial in animal models of Trichinella spiralis infections. 4-Deoxypyridoxine has also been described as an inhibitor of sphingosine-1-phosphate lyase. The inhibition of sphingosine-1-phosphate lyase by 4-Deoxypyridoxine has been shown to prevent cell death of ex-vivo animal pancreatic islets. The use of 4-Deoxypyridoxine to prevent stress-induced apoptosis is suggest that the compound, as well as other inhibitors of sphingosine-1-phosphate lyase, could be used to increase the viability of donor pancreatic tissue in the treatment of diabetes.

<span class="mw-page-title-main">Cys/Met metabolism PLP-dependent enzyme family</span>

In molecular biology, the Cys/Met metabolism PLP-dependent enzyme family is a family of proteins including enzymes involved in cysteine and methionine metabolism which use PLP (pyridoxal-5'-phosphate) as a cofactor.

Phosphoserine transaminase is an enzyme with systematic name O-phospho-L-serine:2-oxoglutarate aminotransferase. This enzyme catalyses the following chemical reaction

Pyridoxal 5′-phosphate synthase (glutamine hydrolysing) (EC 4.3.3.6, PdxST) is an enzyme with systematic name D-ribose 5-phosphate,D-glyceraldehyde 3-phosphate pyridoxal 5′-phosphate-lyase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Toxopyrimidine</span> Chemical compound

Toxopyrimidine is a vitamin B6 antagonist with potent convulsant effects.

Megavitamin-B6 syndrome is a collection of symptoms that can result from chronic supplementation, or acute overdose, of vitamin B6. While it is also known as hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess, megavitamin-b6 syndrome is the name used in the ICD-10.

<span class="mw-page-title-main">3-Hydroxyisonicotinaldehyde</span> Chemical compound

3-Hydroxyisonicotinaldehyde (HINA), also known as 3-hydroxypyridine-4-carboxaldehyde, is a derivative of pyridine, with hydroxyl and aldehyde substituents. It has been studied as a simple analogue of vitamin B6. In 2020, it was reported as having the lowest molecular weight of all dyes which exhibit green fluorescence.

References

  1. 1 2 Leistner E.; Drewke C. (2010). "Ginkgo biloba and ginkgotoxin". Journal of Natural Products. 73 (1): 86–92. doi:10.1021/np9005019. PMID   20041670.
  2. Van Beek T.A.; Montoro P. (2009). "Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals". Journal of Chromatography A. 1216 (11): 2002–2032. doi:10.1016/j.chroma.2009.01.013. PMID   19195661.
  3. 1 2 Scott P.M.; Lau B.Y-P.; Lawrence G.A.; Lewis D.A. (2000). "Analysis of Ginkgo biloba for the presence of ginkgotoxin and ginkgotoxin-5'-glucoside". Journal of AOAC International. 83 (6): 1313–1320. doi: 10.1093/jaoac/83.6.1313 . PMID   11128132.
  4. 1 2 Yoshimura T.; Udaka N.; Morita J.; Jinyu Z.; Sazaki K.; Kobayashi D.; Wada K. (2006). "High performance liquid chromatographic determination of ginkgotoxin and ginkgotoxin-5'-glucoside in Ginkgo biloba seeds". Journal of Liquid Chromatography & Related Technologies. 29 (4): 605–616. doi:10.1080/10826070500531466.
  5. Fiehe K.; Arenz A.; Drewke C.; Hemscheidt T.; Williamson R.T.; Leistner E. (2000). "Biosynthesis of 4'-O-methylpyridoxine (ginkgotoxin) from primary precursors". Journal of Natural Products. 63 (2): 185–189. doi:10.1021/np990414+. PMID   10691705.
  6. 1 2 Kästner U.; Hallmen C.; Wiese M.; Leistner E.; Drewke C. (2007). "The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba". The FEBS Journal. 274 (4): 1036–1045. doi: 10.1111/j.1742-4658.2007.05654.x . PMID   17250738.