Cycasin

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Cycasin
Cycasin.png
Names
IUPAC name
(Z)-1-[(β-D-Glucopyranosyloxy)methyl]-2-methyldiazene 2-oxide
Systematic IUPAC name
(Z)-1-Methyl-2-({[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)diazene 1-oxide
Other names
β-D-Glucosyloxyazoxymethane; Methylazoxymethanol β-D-glucoside; Cycas revoluta glucoside; [(Z)-Methyl-ONN-azoxy]methyl β-D-glucopyranoside [1]
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
MeSH D003492
PubChem CID
UNII
  • InChI=1S/C8H16N2O7/c1-10(15)9-3-16-8-7(14)6(13)5(12)4(2-11)17-8/h4-8,11-14H,2-3H2,1H3/b10-9-/t4-,5-,6+,7-,8-/m1/s1
    Key: YHLRMABUJXBLCK-LBCXAKKBSA-N
  • InChI=1/C8H16N2O7/c1-10(15)9-3-16-8-7(14)6(13)5(12)4(2-11)17-8/h4-8,11-14H,2-3H2,1H3/b10-9-/t4-,5-,6+,7-,8-/m1/s1
    Key: YHLRMABUJXBLCK-LBCXAKKBSA
  • [O-]/[N+](=N/CO[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)CO)C
Properties
C8H16N2O7
Molar mass 252.223 g·mol−1
56.6 g/L [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Cycasin is a carcinogenic and neurotoxic glucoside found in cycads such as Cycas revoluta and Zamia pumila . Symptoms of poisoning include vomiting, diarrhea, weakness, seizures, and hepatotoxicity. In metabolic conditions, cycasin is hydrolyzed into glucose and methylazoxymethanol (MAM), the latter of which dissociates into formaldehyde and diazomethane. [3]

Contents

It induces hepatotoxicity and Zamia staggers, a fatal nervous disease affecting cattle resulting from browsing on the leaves or other parts of cycads. [4]

Sources

Cycasin is found in all known cycad genera and is distributed throughout the body of the plant, but with the highest concentration in the seeds. It is one of several toxins found in cycad plants, along with the neurotoxic amino acid BMAA. The origin and biological role of these toxins is unknown, as there does not appear to be a statistically significant correlation between the concentration of toxic material and the types of herbivory observed in animals consuming the plants. [5] [6]

The enzyme methyl-ONN-azoxymethanol beta-D-glucosyltransferase uses the two substrates UDP-glucose and methyl-ONN-azoxymethanol to produce UDP and cycasin. [7]

Ecological significance

The butterfly Eumaeus atala , whose larvae feed on Z. pumila, contain the poison as a consequence of their diet. [8]

Presence in sago

In order to produce sago, cycasin and other cycad toxins must be removed from the flesh of the plants. The flesh, seeds, and roots of the cycad are first dried and ground into a fine powder, before being submerged in boiling water. The water is then allowed to drain, leaching out the toxic material while leaving the starch behind. The extracted starch is then alternately dried and pounded until a fine powder is obtained. This repeated pounding and leaching process insures that there is as little cycasin as possible left behind. [9]

Structure

Cycasin is a glucose-derived glycoside with a methylazoxymethanol substitution at the beta position.

Stereochemistry at the azoxy group is (Z) (or trans (E) when oxygen removed formally to form azo- group). [10]

Toxicity

Cycasin has an oral LD50 of 500 mg/kg. [11] Exposure to cycasin by injection does not cause any permanent ill effects. [12] As a consequence, consumption is not immediately lethal, but will cause a host of liver and neurological problems, as well as causing cancer with long-term exposure. The mechanism of cycasin's toxicity relies on β-glucosidase enzymes found in the gut. Treatment with β-glucosidase causes cycasin to release methylazoxymethanol (MAM), which spontaneously decomposes to form formaldehyde and methyl-diazonium. The amount of formaldehyde released is too small to induce toxicity, but methyl-diazonium is a potent methylating agent. The presence of this molecule methylates DNA, causing long-term damage and potentially giving rise to cancers. [3]

Methylazoxymethanol (MAM) Methylazoxymethanol.svg
Methylazoxymethanol (MAM)

Symptoms

Early symptoms of cycasin poisoning are vomiting, nausea, abdominal pain, and diarrhea. Later stages of poisoning manifest as liver dysfunctions. [13]

Zamia staggers

Livestock that consume raw leaves, nuts, and flour of cycads develop a neurologic syndrome known as zamia staggers, named for the cycad genus Zamia native to Central and South America. It is clinically characterized by weight loss followed by lateral swaying of the hind quarters, with weakness, ataxia, and proprioceptive defects in the rear limbs, and results in demyelination and axonal degeneration in the brain, spinal cord, and dorsal root ganglia. [4]

Suspected association with Lytico-bodig disease

The Lytico-bodig disease, also known as lateral sclerosis-parkinsonism-dementia, is a neurodegenerative disease of unknown origin that occurs exclusively in the Chamorro people of the island of Guam that has characteristics of both amyotrophic lateral sclerosis (ALS) and parkinsonism. It is characterized by muscle atrophy, maxillofacial paralysis, inability to speak or swallow, and dementia. The disease is fatal in all cases, with the diaphragm and respiratory accessory muscles becoming paralyzed in the later stages of the disease. [14]

Observation of the diets of the native Chamorro people led to the creation of the so-called "Cycad hypothesis." Starches prepared from the seeds of a native cycad species, Cycas micronesica , are used to create the sago-like flour fadang, which forms a major part of the diet of the Chamorro people. As the seeds contain the highest amount of the toxin found in the plant, it was proposed that a dietary explanation relating to the consumption of poorly processed fadang was poisoning the natives. After failing to reproduce the symptoms of the disease in animal models, the hypothesis was rejected. [14] Though the initial cycad hypothesis was rejected, a revised form of the hypothesis was proposed by Paul Alan Cox and Oliver Sacks after observing other elements of the Chamorro diet, specifically flying foxes. The bats accumulate BMAA in their fat by consuming cycad seeds, resulting a in a high concentration of the neurotoxin. [15]

Cycas micronesica, one of the cycad species consumed by the Chamorro Cycas micronesica photo courtesy A. Gawel (15391498081).jpg
Cycas micronesica , one of the cycad species consumed by the Chamorro

See also

Related Research Articles

<span class="mw-page-title-main">Poison</span> Substance that causes death, injury or harm to organs

A poison is any chemical substance that is harmful or lethal to living organisms. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broad sense.

<span class="mw-page-title-main">Sago</span> Starch extracted from tropical palm stems

Sago is a starch extracted from the pith, or spongy core tissue, of various tropical palm stems, especially those of Metroxylon sagu. It is a major staple food for the lowland peoples of New Guinea and the Maluku Islands, where it is called saksak, rabia and sagu. The largest supply of sago comes from Southeast Asia, particularly Indonesia and Malaysia. Large quantities of sago are sent to Europe and North America for cooking purposes. It is traditionally cooked and eaten in various forms, such as rolled into balls, mixed with boiling water to form a glue-like paste (papeda), or as a pancake.

<span class="mw-page-title-main">Cycad</span> Division of naked seeded dioecious plants

Cycads are seed plants that typically have a stout and woody (ligneous) trunk with a crown of large, hard, stiff, evergreen and (usually) pinnate leaves. The species are dioecious, that is, individual plants of a species are either male or female. Cycads vary in size from having trunks only a few centimeters to several meters tall. They typically grow very slowly and live very long. Because of their superficial resemblance, they are sometimes mistaken for palms or ferns, but they are not closely related to either group.

<span class="mw-page-title-main">Excitotoxicity</span> Process that kills nerve cells

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate.

<span class="mw-page-title-main">Cyanotoxin</span> Toxin produced by cyanobacteria

Cyanotoxins are toxins produced by cyanobacteria. Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they can poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.

<i>Zamia furfuracea</i> Species of cycad

Zamia furfuracea is a cycad endemic to southeastern Veracruz state in eastern Mexico.

<i>Cycas revoluta</i> Species of plant

Cycas revoluta is a species of gymnosperm in the family Cycadaceae, native to southern Japan including the Ryukyu Islands. It is one of several species used for the production of sago, as well as an ornamental plant. The sago cycad can be distinguished by a thick coat of fibers on its trunk. The sago cycad is sometimes mistakenly thought to be a palm, although the only similarity between the two is that they look similar and both produce seeds.

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

Abrin is an extremely toxic toxalbumin found in the seeds of the rosary pea, Abrus precatorius. It has a median lethal dose of 0.7 micrograms per kilogram of body mass when given to mice intravenously. The median toxic dose for humans ranges from 10 to 1000 micrograms per kilogram when ingested and is 3.3 micrograms per kilogram when inhaled.

Lytico-bodig (also Lytigo-bodig) disease, Guam disease, or amyotrophic lateral sclerosis-parkinsonism-dementia (ALS-PDC) is a neurodegenerative disease of uncertain etiology endemic to the Chamorro people of the island of Guam in Micronesia. Lytigo and bodig are Chamorro language words for two different manifestations of the same condition. ALS-PDC, a term coined by Asao Hirano and colleagues in 1961, reflects its resemblance to amyotrophic lateral sclerosis (ALS), Parkinson's disease, and Alzheimer's disease.

β-Methylamino-<small>L</small>-alanine Chemical compound

β-Methylamino-L-alanine, or BMAA, is a non-proteinogenic amino acid produced by cyanobacteria. BMAA is a neurotoxin. Its potential role in various neurodegenerative disorders is the subject of scientific research.

<i>Cycas micronesica</i> Species of cycad

Cycas micronesica is a species of cycad found on the island of Yap in Micronesia, the Marianas islands of Guam and Rota, and The Republic of Palau. It is commonly known as federico nut or fadang in Chamorro. The species, previously lumped with Cycas rumphii and Cycas circinalis, was described in 1994 by Ken Hill. Paleoecological studies have determined that C. micronesica has been present on the island of Guam for about 9,000 years. It is linked with Lytico-Bodig disease, a condition similar to amyotrophic lateral sclerosis (ALS), due to the neurotoxin BMAA found in its seeds, which were a traditional food source on Guam until the 1960s. The neurotoxin is present due to its symbiosis with cyanobacteria.

<i>Macrozamia dyeri</i> Species of cycad

Macrozamia dyeri, known as djeeri, is a species of plant in the family Zamiaceae. It is endemic to Western Australia, occurring near Esperance. The seeds are consumable when prepared correctly and were an important resource to people of the region, but the plant is otherwise toxic to many species.

<i>Macrozamia glaucophylla</i> Species of plant

Macrozamia glaucophylla is a species of cycad from the genus Macrozamia and the family Zamiaceae. Endemic to New South Wales, Australia, this species has features that resembles palms, although both species are taxonomically quite different. The current population trend of Macrozamia glaucophylla is stable with 2,500 to 10,000 mature individuals. The species are found in several habitats including forest and savanna. Ecologically, Macrozamia glaucophylla lives in terrestrial system, a land-based community of organisms where the biotic and abiotic components interact in the given area.

<i>Macrozamia heteromera</i> Species of plant

Macrozamia heteromera is a species of cycad in the family Zamiaceae initially discovered by Charles Moore in 1858 and is endemic to New South Wales, Australia. It can be found in the north-western region of New South Wales within the Warrumbungle mountains and further south west towards the Coonabarabran district. It is a low trunked cycad usually at a height below 1 metre and can be found in dry sclerophyll woodlands. M. heteromera can be distinguished from the rest of the Macrozamia genus by its mid-green, narrow, usually divided pinnae and divided seedling pinnae. It is a plant that has toxic seeds and leaves, a characteristic common to cycads. However, after proper preparation and procedure, the seeds are fine for consumption.

<i>Macrozamia miquelii</i> Species of cycad

Macrozamia miquelii, is a species of cycad in the plant family Zamiaceae. It is endemic to Queensland and New South Wales in Eastern Australia. Located within sclerophyll forests dominated by eucalyptus trees, the cycad grows on nutrient-poor soils. It is recognised within the Zamiaceae family for its, medium height at 1 m, intermediate size of male and female cones and lighter green leaves compared to other cycads within the plant family of Zamiaceae. The seeds have an orange red sarcotesta which attracts fauna consumption, allowing a mutualistic seed dispersal for the cycad. These seeds are also edible for human consumption if prepared correctly to remove the toxins.

<i>Macrozamia riedlei</i> Species of cycad

Macrozamia riedlei, commonly known as a zamia or zamia palm, is a species of cycad in the plant family Zamiaceae. It is endemic to southwest Australia and often occurs in jarrah forests. It may only attain a height of half a metre or form an above trunk up to two metres with long arching fronds of a similar length. The giant cones amidst the crown of palm-like fronds contain edible seeds surrounded by red sarcotesta. The seeds are consumed by birds and animals, and can be a favoured part of the human diet when prepared correctly. M. riedlei benefits from a close association with bacteria that fix nitrogen, which also produce substances found throughout the plant that are toxic to some animals when consumed. The species is cultivated for ornamental use in urban and domestic environments.

In enzymology, a methyl-ONN-azoxymethanol beta-D-glucosyltransferase is an enzyme that catalyzes the chemical reaction

Zamia staggers is a fatal nervous disease affecting cattle in areas where they browse on the leaves or fruit of cycads—in particular, those of the genus Zamia. It is characterised by irreversible paralysis of the hind legs because of the degeneration of the spinal cord. It is caused by the toxins cycasin and macrozamin, β-glycosides of methylazoxymethanol (MAM), and which are found in all cycad genera.

<span class="mw-page-title-main">Toxalbumin</span> Toxic plant proteins

Toxalbumins are toxic plant proteins that disable ribosomes and thereby inhibit protein synthesis, producing severe cytotoxic effects in multiple organ systems. They are dimers held together by a disulfide bond and comprise a lectin part which binds to the cell membrane and enables the toxin part to gain access to the cell contents. Toxalbumins are similar in structure to AB toxins found in cholera, tetanus, diphtheria, botulinum and others; and their physiological and toxic properties are similar to those of viperine snake venom.

<i>Zamia integrifolia</i> Species of cycad

Zamia integrifolia, also known as coontie palm, is a small, tough, woody cycad native to the southeastern United States, the Bahamas, Cuba, and the Cayman Islands.

References

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  11. Sax, N Irving; Feiner, Benjamin (1984). Dangerous properties of industrial materials (6th ed.). New York: Van Nostrand Reinhold. p. 828. ISBN   0442283040.
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  15. Cox PA, Banack SA, Murch SJ (2003). "Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam". PNAS. 100 (23): 13380–13383. Bibcode:2003PNAS..10013380C. doi: 10.1073/pnas.2235808100 . PMC   263822 . PMID   14612559.