Phytochemicals & Mycochemicals

This database details pharmacologically significant phytochemical and mycochemical compounds found in local species. The aim is to identify substances and explore ways to utilize or denature these compounds.

"While many of the thousands of chemicals in plants can be poisonous, their concentrations are for the most part too low to be of concern... generally one would have to consume prodigious amounts... A famous example was provided by Basil Brown... who in 10 days in 1974 drank about 45 L of carrot juice... he was dead of severe liver damage." [Small CH]

Google Gemini - Page organized using AI prompts. Some information, those without sources, are from unspecified AI sources and are included only as a starting point for further research. (This page needs scrutiny)

Top | Alkaloids | Phenolics | Terpenoids | Glycosides | Other

1. Alkaloids (Nitrogen-Containing)

Alkaloids are nitrogen-containing organic compounds, usually basic, that produce distinct physiological effects. They are widely distributed in higher plants.

"Their definition is problematic... Except for the fact that they are all nitrogen-containing compounds, no general definition fits all alkaloids." [MHC Hoffman]

"Despite the difficulty in defining them, most alkaloid share physical and chemical properties. They are usually insoluble or sparingly soluble in water... annual plants contain larger amounts of alkaloids than do perennials." [MHC Hoffman]

"Alkaloids are nitrogen heterocyclic substances, found in over 13 000 species... Alkaloids have been identified in vacuoles, chloroplasts, and extraplasmatic space." [Singh APB]

Alkamides

"In alkamides, amines are combined with unsaturated fatty acids by amide linkages... responsible for the sharp, burning or tingling taste associated with herbs... such as prickly ash bark and Echinacea." [Pengelly TCMP]

  • Spilanthol: Predominant alkamide in Spilanthes sp.; displays analgesic and immunomodulatory properties.
  • Pellitorine: Found in Piper longum; effective insecticidal agent against housefly and mosquito.
  • Echinacea Alkamides: "More than 20 alkamides... are found in the roots... inhibit COX-2-dependent PGE2 formation."

Amines (Biogenic)

"Biologically active amines are normal constituents of many foods... These low molecular weight organic bases do not represent any hazard unless large quantities are ingested."

  • Melatonin: An indolamine found in edible fruits (grape, banana), nuts (walnuts), and seeds. Regulates circadian rhythm and has antioxidant effects.
  • Polyamines: Spermine, spermidine, and putrescine found in plants. Cooking (boiling) can reduce polyamine content by transfer to water.

Berberine

Class: Isoquinoline Alkaloid

Berberine has marked antibacterial effects and is used as a bitter tonic. Since it is not appreciably absorbed by the body, it is used orally in the treatment of various enteric infections. "Berberine has antifibrillatory activity... and anticonvulsant, sedative, uterine stimulant activities."

Cytisine

Class: Quinolizidine Alkaloid

"Cytisine binds strongly to nicotinic receptors, causing initially stimulation and at higher doses blockade... similar to the effects of curare." It has been used as an insecticide and is the lead compound for varenicline (smoking cessation drug).

  • Sources: Laburnum spp., Cytisus scoparius (Scotch Broom), Sophora secundiflora (Mescal bean).
  • Toxicity: "A piece of the root the size of a pea can kill a man." Teratogenic in rabbits.

Ibotenic Acid

Class: Isoxazole Alkaloid

Found in Amanita muscaria and Amanita pantherina. "The effects... often are described as inebriation... Nausea is usually the first symptom... The final stage usually involves a deep coma-like sleep."

Muscarine

Class: Alkaloid

"The first drug known to have a selective action on organs innervated by the autonomic nervous system." Symptoms include profuse sweating, salivation, and lacrimation (PSL syndrome) within 15-30 minutes.

Muscimol

Class: Isoxazole Alkaloid

A centrally acting principle of the mushroom Amanita muscaria, produced by the decarboxylation of Ibotenic acid. It is a potent GABA-A receptor agonist.

Slaframine

Class: Indolizidine Alkaloidal Mycotoxin

Produced by the fungus Rhizoctonia leguminicola on Red Clover (Trifolium pratense). Causes "slobbers syndrome" (profuse salivation) in livestock. "Slaframine is stable in dried hay... removal of contaminated hay allows recovery."

Solanine & Solanidine

Class: Steroidal Glycoalkaloid

Toxic alkaloids found in Solanaceous plants. "Solanine... inhibits RNA reverse transcriptase... and causes hemolysis of membranes." Toxicity is not significantly reduced by boiling. Frying at high temps (>170°C) degrades it partially.

  • Sources:
    • Solanum tuberosum (Potatoes): "Green" potatoes or sprouts contain high levels.
    • Solanum nigrum (Black Nightshade): "All parts... except the ripe fruit contain the toxic glycoalkaloid solanine."
    • Solanum dulcamara (Bittersweet): "Whole plant is toxic."
    • Solanum melongena (Eggplant), Lycopersicon esculentum (Tomato).
  • Toxicity: Nausea, diarrhea, headache, burning throat, cardiac dysrhythmia. Doses of 3-6 mg/kg can be fatal.

Sparteine

Class: Quinolizidine Alkaloid

Major alkaloid in Cytisus scoparius (Scotch Broom). "Reported to have a quinidine-like action... used to treat cardiac arrhythmias... also stated to be a powerful oxytocic drug." Toxic doses cause vomiting and respiratory paralysis.

Veratridine

Class: Steroid-derived Alkaloid

A neurotoxin that binds to voltage-gated sodium channels, causing them to stay open. "The toxic effects... are more morbidly impressive and violent than those from coniine."

  • Sources: Veratrum viride (False Hellebore), Schoenocaulon officinale.

Vincamine

Class: Indole Alkaloid

Found in Vinca minor (Periwinkle). "Used by the pharmaceutical industry as a cerebral stimulant and vasodilator... indicated in the treatment of tinnitus."

2. Phenolics

"Phenolic compounds... are the important groups of compounds occurring in plants... comprising at least 8,000 different known structures."

Flavonoids

In chloroplasts, flavonoids act as primary antioxidants. Includes sub-groups like Flavonols (Quercetin), Flavones (Apigenin), and Isoflavones (Genistein). "Glycosides are linked to the phenolic hydroxyls... commonly reported benefits of flavonoid glycosides are anti-oxidants and anti-inflammatory activities."

  • Anthocyanins: Responsible for red/blue/purple pigments in berries. See full profile.

Lignans & Lignin

Lignin: A major component of dietary fiber. "Antitumor, antiviral and immunopotentiating activities have been attributed to... lignin-related materials."

Lignans: Dimeric compounds (e.g., Podophyllotoxin). "Podophyllotoxin... exhibits pronounced biological activity mainly as strong antiviral agents and as antineoplastic drugs." Found in Podophyllum peltatum.

Tannins

"Powerful antioxidant agents because they have many hydroxyl groups... classified into two classes: hydrolysable tannins (gallo- and ellagi-tannins) and condensed tannins (proanthocyanidins)."

Coumarins

Lactones derived from cinnamic acid. "Occur in fruits, olive oil, vegetables... shown to have antioxidant and anticancer effects."

  • Esculetin: Shows anti-tumor and anti-inflammatory activities.
  • Aesculin: Found in Horse Chestnut (Aesculus hippocastanum). "Effective... for chronic venous insufficiency (CVI), haemorrhoids and post-operative oedema."

Usnic Acid

A dibenzofuran derivative found exclusively in lichens (Usnea spp.). "Believed that usnic acid protects the lichen from adverse effects of sunlight exposure and deters grazing animals." Potent antibiotic against Gram-positive bacteria.

Vulpinic Acid

A pulvinic acid derivative found in Wolf Lichen (Letharia vulpina). "Used traditionally as a poison for foxes and wolves... toxic principle is... poisonous to all meat eaters but also to insects and mollusks."

3. Terpenoids (Isoprenoids)

Derived from isoprene units (C5). This is the largest class of plant secondary metabolites.

Aucubin

Class: Iridoid Glycoside (Monoterpene)

Found in Plantago and Cornus species.

"Aucubin is found in common verbena. Aucubin is a monoterpenoid based compound. Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton. Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides (Eucommiaceae), and Plantago asiatic (Plantaginaceae), etc, plants used in traditional Chinese and folk medicine. Aucubin was found to protect against liver damage induced by carbon tetrachloride or alpha-amanitin in mice and rats when 80 mg/kg was dosed intraperitoneally. Aucubin has been shown to exhibit anti-proliferative and apoptotic functions. Aucubin has shown effectiveness as antifungal and suggests its promising potential use as solution for C. albicans biofilm-related infections. Aucubin has a range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities."

References

Betulin

Class: Triterpenoid (Lupane)

Found in the bark of birch (Betula) and Alder.

"Betulin, belonging to lupane class, is the most abundant triterpenoid in the nature, which is the precursor of betulinic acid found in plant species of the Betulaceae family. For instance, the bark of hazel (Corylus avellana), hornbeam (C. betulus) and a number of Alnus species are the main source of the compound." [Saeidnia NANAD]

"The compound is used in cosmetic products and its derivatives are applied in production of plastic materials. Betulinic acid exerted cytotoxic activity toward neuroblastoma cells, glioblastoma and melanoma cell lines." [Saeidnia NANAD]

Cucurbitacins

Class: Triterpenoids

"Cucurbitacins are extremely bitter and toxic tetracyclic terpenoids (lanostane derivatives) associated primarily with Cucurbitaceae family. These are also reported from plants belonging to other families like Brassicaceae, Begnoniaceae, Datiscaceae, Euphorbiaceae, Rosaceae and Labiaceae. At least sixteen species of the genus Ibris are known to produce this class of compounds, 12 of these contain cucurbitacin E and I reported as antifeedant against flea beetle, Phyllotreta nemorum (Linnaeus). Iberis amara, like most other crucifers, contains sulphur-containing glucosinolates, which act as oviposition and feeding stimulants. However, the plant is rejected by insects due to occurrence of specific cucurbitacins-I and II (158, 159) (Sachdev-Gupta et al. 1993)" [Koul PB]

Distribution

  • Anagallis arvensis - Scarlet Pimpernel [PDR]
  • Citrullus colocynthis
    - Bitter Apple " Cucurbitacins: including cucurbitacin E-, J-, L-glucosides " [PDR]
  • Cucurbitaceae [EMNMPV.2]
  • Cucumis sativus ( Cucurbitacin I ) [EMNMPV.2]
  • Cucurbita pepo (fruit)( cucurbitacin
    L & K) [EMNMPV.2]
  • Gratiola officinalis - Hedge-Hyssop ([PDR]
  • Iberis amara - Bitter Candytuft ("Cucurbitacins (0.2 to 0.4%): particularly cucurbitacins E and I ") [PDR]
  • Lepidium sativum - Garden Cress [PDR]
  • Momordica charantia ( Fourteen cucurbitane triterpenoids ) [EMNMPV.2]

"Cucurbitacin C is found only in C. sativus (Enslin and Rehm 1958)." [EMNMPV.2]

Adverse Health Effects

  • "The cucurbitacins contained in the seeds [of Iberis amara] are toxic, cytotoxic and generally irritating to the small and large intestines." [PDR]
  • Citrullus colocynthis "... has a strongly irritating (and painful) effect on mucous membranes due to its cucurbitacin glycoside content, out of which cucurbitacins are released in watery environments." [PDR]
  • Anagallis arvensis "Large doses or long-term administration could lead to gastroenteritis and nephritis, due to the cucurbitacins content of the drug." [PDR]

Activities

  • "Besides cytotoxicity and anti-cancer activity, cucurbitacins also exhibited further wide ranging in-vitro or even in-vivo pharmacological effects, such as purgative, anti-inflammatory, and anti-fertility activities (Chen et al. 2005)." [EMNMPV.2]
  • "Cucurbitacin E was identified as a sterol with potent growth inhibitory activity in-vitro against prostate carcinoma explants (IC50 of 7–50 nM in 2- to 6-day exposures) (Duncan et al. 1996).... Fruits were also found to contain cucurbitaglycosides cucurbitane triterpenoids with a purine unit, cucurbitaglycoside A and cucurbitaglycoside B which showed cytotoxic activity against the human epithelial carcinoma cell line HeLa with IC 50 of 17.2 and 28.4 mg/ml, respectively (Wang et al. 2008)." [EMNMPV.2]
  • "Among the secondary metabolites of M. charantia, cucurbitane-type triterpenoids are one of the main bioactive constituents. These compounds and their aglycones have shown various pharmacological and biological activities including antidiabetic, anti-obesity, anticancer, anti-tumour, anti-HIV, antidiabetic, antifeedant and antioviposition activities (Raman and Lau 1996; Grover and Yadav 2004; Beloin et al. 2005; Chen et al.2005; Lee et al. 2009; Nerurkar and Ray 2010) .... Five cucurbitacins, kuguacins A- E (1–5), together with three known analogues, were isolated from bitter melon roots by (Chen et al. 2008) . Compounds 3 and 5 showed moderate anti-HIV-1 activity and exerted minimal cytotoxicity. Cucurbitane triterpenoids, kuguacins F-S (1–14), isolated from bitter melon vines and leaves exhibited weak anti-HIV-1 activities in-vitro (Chen et al. 2009.) " [EMNMPV.2]

Antifeedant: "The Diabroticite phagostimulant and arrestant cucurbitacins (Metcalf et al. 1980), antifeedant to most other insects (Tallamy et al. 1997a), are present in cucurbit anthers and other flower parts (Anderson and Metcalf 1987) but absent from pollen.... The usefulness of Diabroticites as model pest insects for taste receptor research derives from their i) diverse host plant associations, ii) extreme larval-to-adult host species shifts, iii) global agricultural pest status, iv) high and uniform sensitivities to the most potent animal phago-stimulants and -deterrents (e.g. cucurbitacins and azadirachtin), and v) their ease of behavioural and electrophysiological testing relative to gustation (Mullin et al. 1994). These chemoreception studies benefited from simultaneous comparison of structure-activity relationships for both feeding stimulants and deterrents using complete dose-response ranges, since stimulants can become antifeedants at high doses.... The strong phagostimulatory action of cucurbitacins on adult Diabroticite beetles has led to their use in baits laced with small amounts of carbaryl (Metcalf and Metcalf 1992) that are now marketed (e.g. Slam® and Adios® from BASF Corp. formerly MicroFlo Co.; Compel® from Ecogen, now Monsanto Co.). These baits have sufficient efficacy to manage vectoring of bacterial wilt by Diabroticites (Fleischer and Kirk 1994).... Cucurbitacin baits based on dried buffalo gourd, Cucurbita foetidissima HBK, powder greatly reduce insecticide inputs for rootworm control, and, as a chemical mixture in contrast to a single component, may retard the development of gustatory habituation and insensitivity, and are antifeedant for many non-target species (Tallamy et al. 1997a). Baits incorporating cucurbitacin phagostimulants specific for adult Diabroticites are effective alternatives to soil insecticides used for larval control." [Koul PB]

Herbivore Adaptations to curcurbitans: " An interesting behavioural aspect relates to the canalicular defenses wherein plant secretion stored within canal systems interferes with foraging by nonadapted caterpillars. Adapted species overcome this by cutting trenches. Petiole constriction and trenching behaviour are well evident in the danaine caterpillars, which feed not only on closely related Apocyanace and Asclepidaceae, but also on the Moraceae; all the three groups producing alkaloids, pyridines and cardenolides. Similarly, beetles of the genus Epilachna have shown the trenching behaviour cucurbitaceous hosts to prevent an influx of bitter cucurbitacins at the feeding site (Doussurd 1993)." [Koul PB]

Saponins

Class: Triterpene or Steroid Glycosides

Compounds that produce soap-like foam. "Cause hemolysis after intravenous introduction." View full Saponin profile.

Carotenoids (Tetraterpenoids)

"Carotenoids, which occur in all plants, bacteria, and fungi, are probably the most widely distributed of all natural pigments; they are involved in many fundamental processes such as photosynthesis and mammalian vision. These highly unsaturated lipids also serve as vegetative, floral, and fruit pigments in plants and as pigments in the feathers of birds, outer parts of insects, as well as the skins of fish and other animals (Britton, 1976, 1983; Buchecker, 1982; Kayser, 1982)." [Seiger PSM]

"The properties and structures of tetraterpenes differ markedly from those of the lower terpenes (Ramage, 1972). Carotenoids (the major representatives of this class) are mostly linear polyene systems. The high degree of unsaturation renders them both heat and light sensitive. These compounds are an experimentally demanding group of compounds with which to work (Britton, 1983; Ramage, 1972) .. Methods for purification of carotenoids are similar to those for other terpenoids, but, because of the highly unsaturated nature of the compounds, special care must be taken (Britton, 1991). Care to avoid oxidation is most important; extracts that contain chlorophyll must be handled with special care." [Seiger PSM]

"Most carotenoids are colored and absorb light in the visible range of the spectrum. The specific wavelength of absorption is a function of the structure, in particular, the number and arrangement of double bonds and oxygenated substituents, but also the solvent and other factors (Britton, 1983). Most carotenoids are yellow to orange (sometimes red) when isolated." [Seiger PSM]

"As mentioned above, the leaves of all green plants contain the same major carotenoids: B-carotene (1), lutein (2), violaxanthin (3), and neoxanthin (4). Smaller amounts of other compounds are often present." [Seiger PSM]

"Animals require vitamin A (retinol) (19) or a carotenoid precursor for normal growth and vision (Liu, 1982). An early symptom of vitamin deficiency is a decreased ability to see in dim light." [Seiger PSM]

"Many of the colors used for aposematic labeling by animals (bright reds, oranges, and yellows) are produced by carotenoid pigments (Rothschild, 1975, 1978). These compounds ultimately arise from plants (or from symbiotic bacteria?), as animals cannot synthesize carotenoids." [Seiger PSM]

"Carotenoids, especially J3-carotene (I), often have heen used for coloring food products. This is especially common in such fatry foods as margarine. Bixa orellana, achiote or annatto, has been used as a food colorant and flavoring in Latin America for generations, a practice now common in most tropical areas of the world. The seeds of this plant contain bixin (31), the methyl ester of 6,6'·diapocarotenoic acid. In the Iberian peninsula, the use of Crocus sativus (saffron, Iridaceae) as a food coloring material is widespread. Some of the yellow pigments of this plant, such as crocein (29), also are carotenoids (Rothschild, 1975). Many carotenoids (e.g., J3-carotene) are antioxidants. This property has led to the suggestion that they are important in the diet and can afford protection against some forms of cancer and other diseases (Britton, 1991)." [Seiger PSM]

Strigolactones

  • Found in; Orobanche, Alectra and Striga genera [Roy PP]

"Strigolactones are signaling compounds made by plants. They have two main functions: first, as endogenous hormones to control plant development, and second as components of root exudates to promote symbiotic interactions between plants and soil microbes. Some plants that are parasitic on other plants have established a third function, which is to stimulate germination of their seeds when in close proximity to the roots of a suitable host plant. It is this third function that led to the original discovery and naming of strigolactones." (Smith, S.M.,2014)

"Strigolactones are made from carotenoids, which in turn are made from building blocks called terpenes or isoprenes. Carotenoids and hence strigolactones can therefore be described as terpenoids or isoprenoids. .... Carotenoids are also precursors of abscisic acid, a hormone that controls the response of plants to environmental stress. The biosynthetic pathway to strigolactones has recently been shown to involve three chloroplast enzymes that convert beta-carotene to a lactone, given the name carlactone [11] .... This is then oxidized in the cytosol of the cell to produce strigolactones. More recently an ATP-dependent transporter protein has been discovered that transports strigolactones out of the cell, either for long distance translocation within the plant or for exudation from roots [12]." (Smith, S.M.,2014)

"Recently, it was shown that strigolactones or derivatives thereof are identical with the postulated shoot multiplication signal (SMS) which regulates apical dominance in vascular plants (Gomez-Roldan et al., 2008; Umehara et al., 2008; Dun et al., 2009)."[Roy PP]

"Lateral bud growth is inhibited by auxins transported down from the shoot apex and by strigolactones transported upwards from the root. However, cytokinins, also transported from root to shoot, can promote bud outgrowth [22]. These different signals are modulated in response to different environmental factors, such as light and nutrients, and are integrated through crosstalk between biosynthesis and signaling pathways...." (Smith, S.M.,2014)

References

  • (Smith, S.M.,2014) Smith, S.M. Q&A: What are strigolactones and why are they important to plants and soil microbes?. BMC Biol 12, 19 (2014). https://doi.org/10.1186/1741-7007-12-19

4. Glycosides

"When ingested, glycosides are readily broken down by enzymes or acids... The poisonous qualities... are determined by their aglycones."

Arbutin

Class: Phenolic Glycoside

Found in Bearberry (Arctostaphylos uva-ursi). "Principal antibacterial constituent... used in cosmetics as a skin lightening Agent."

Cyanogenic Glycosides

Release Hydrogen Cyanide (HCN) upon hydrolysis. "10 bitter almonds are said to be fatal for a child, 60 for an adult."

  • Amygdalin: Found in bitter almonds, apricot pits, cherry leaves.
  • Prunasin: Found in Wild Cherry bark.
  • Linamarin: Found in Flax and Cassava. "In populations where cassava is a staple crop, care is taken to soak, grate, and ferment... allowing release of HCN."
  • Triglochinin: Found in Triglochin maritima (Arrowgrass) and Alocasia.

Cardiac Glycosides

Steroidal glycosides that affect heart rhythm. "Toxic doses... can kill by causing cardiac arrest."

  • Digitoxin: Found in Foxglove (Digitalis purpurea).
  • Sources: Apocynum (Dogbane), Asclepias (Milkweed).

Glucosinolates

Sulfur-rich compounds in Brassicaceae. "Hydrolysis... produces isothiocyanates... function as cancer-preventing agents, biopesticides, and flavor compounds."

Ptaquilosides

Class: Norsesquiterpene Glucoside

Found in Bracken fern (Pteridium aquilinum). "Regarded as the ultimate carcinogen... Hydrolysis... leads to pterosins... unstable dienone."

Salicin

Class: Phenolic Glycoside

Found in Willow (Salix). "Has anti-inflammatory properties probably due to its oxidation into salicylic acid."

5. Alcohols, Fatty Acids, Peptides & Enzymes

Cicutoxin & Oenanthotoxin

Class: Polyacetylenes (Fatty Alcohols)

"Beside amatoxins, cicutoxin is the most lethal plant toxin in North America... acts as a convulsant."

  • Sources: Cicuta spp. (Water Hemlock). "A piece the size of a pea can kill a man."
  • Oenanthotoxin: Found in Oenanthe crocata. "Fatal quantity... may be as low as 10 to 20 mg."

Falcarinol

Class: Polyacetylene

Found in Apiaceae (Carrot, Celery) and Araliaceae (Ivy, Ginseng). "Contact with leaves... can induce dermatitis... [but] demonstrated interesting bioactivities including antibacterial... and anticancer."

Alkynes & Polyacetylenes

Class: Unsaturated Hydrocarbons

Alkynes are hydrocarbons defined by the presence of at least one carbon-carbon triple bond. While polyacetylenes (like Cicutoxin) are common toxins, monoacetylenes are rarer.

  • Tariric Acid: Found in Picramnia spp. It was the first naturally occurring fatty acid discovered containing a triple bond. [Marchant, Yu Yoke.,1985]

Oligothiophenes

Class: Heteroaromatic Compounds

Short chains of thiophene rings, often found in the Asteraceae family. Known for anti-microbial, anti-inflammatory, and insecticidal properties.

  • alpha-Terthienyl: Found in Marigolds (Tagetes patula). [Marchant, Yu Yoke.,1985]

Sorbitol

Class: Sugar Alcohol

Found in Mountain Ash (Sorbus aucuparia). "~60% as sweet as sugar... Ingesting large amounts... can lead to abdominal pain... and severe diarrhea."

Linoleic Acid

Class: Essential Fatty Acid (Omega-6)

Found in Aesculus seeds and Allium leaves. "Human body cannot synthesize it... anti-inflammatory, acne reductive."

Non-protein Amino Acids (NPAAs)

Class: Nitrogenous Secondary Metabolites

Over 700 non-protein amino acids have been isolated from plants. They often act as antimetabolites, mimicking the structure of protein amino acids to disrupt protein synthesis in herbivores. [Rosenthal HerbV1]

"Amino acids are essential building blocks of living organisms. Various amino acids are incorporated into proteins and are, therefore, called proteinogenic. Besides these, there are a large number of non-proteinogenic amino acids that occur in living organisms. Some of the latter are incorporated into antibiotics and other toxins 92, 110, such as dehydroalanine, which is part of the toxic microcystins produced by cyanobacteria of the genus Microcystis 66. Others are toxins on their own such as 2-amino-3-butynoic acid 57 or function as signalling molecules, notably glycine as a neurotransmitter. Still others are metabolites in the synthesis or degradation pathways of defence chemicals such as glucosinolates 26." (Fichtner et al.,2017)

"Natural or chemically designed and synthesized amino acids, which are non-genetically coded, are considered as non-proteinogenic amino acids. In a more rigorous classification for non-proteinogenic amino acids, we consider all amino acids different in structure from the 20 proteinogenic natural amino acids encoded by the universal genetic code." (Kasperkiewicz et al.,2012)

"For a long time, non-proteinogenic amino acids have attracted considerable interest from medicinal chemists as very attractive scaffolds in the design of molecules with potential biological activity. The variety of structural modifications is theoretically unlimited and the universe of new, interesting structures is growing rapidly." (Kasperkiewicz et al.,2012)

"Most non-proteinogenic amino acids are found within fungi, with particularly many produced by Amanita species as defence chemicals. Several are incorporated into peptide antibiotics. Some of the amino acids occur due to broad substrate specificity of the branched-chain amino acid synthesis pathways. A large variety of amino acids were also found in the Murchison meteorite." (Fichtner et al.,2017)

"These amino acids are hydrophobic and, if incorporated into cytosolic proteins, mainly (but not exclusively) occur in the interior of proteins, which is called the hydrophobic core. Hydrophobicity increases with increasing number of C atoms in the hydrocarbon chain [7]. This implies that, with the exception of alanine and glycine, which can be localized in the interior or at the outside, aliphatic amino acids prefer to remain inside cytosolic proteins or in transmembrane domains." (Fichtner et al.,2017)

"In addition to the canonical 20 amino acids that constitute the essential building blocks of proteins, plants produce a wide variety of non-proteinogenic amino acids (NPAAs; Fowden, 1981, Rosenthal, 1982, Barrett, 1985, Bell, 2003). Some of these plant metabolites are components of central metabolism, serving as intermediates in biosynthetic pathways or as signaling molecules during plant stress responses." (Jander et al.,2020)

"Non-proteinogenic amino acids play very important roles in peptide and drug discovery research. Good examples are amino acids used in the treatment of Parkinson’s disease, e.g., L-DOPA (l-3,4-dihydroxyphenylalanine), or drugs used to alleviate high blood pressure symptoms, e.g., enalapril, which contains hPhe (L-homophenylalanine)" (Kasperkiewicz et al.,2012)

1-aminocyclopropane carboxylate (ACC)
arginosuccinate
β-tyrosine
citrulline
cystathionine
hypoglycin A 		homocysteine
homoserine
ornithine
pipecolic acid
γ-aminobutyric acid
  • Mimosine: Found in Mimosa and Leucaena.
  • Indospicine: Found in Indigofera.
  • Canavanine: (See details below).

β-Amino acids

"β-Amino acids, which have the amino group attached to the β-carbon rather than the adjacent α-carbon, have been reported in many plant species (Kudo et al., 2014). Whereas, some β-amino acids, for instance β-tyrosine, have likely defensive functions in plants (Yan et al., 2015), others are essential components of primary metabolism. Parthasarathy et al. review the biosynthesis and function of β-alanine, which is not only a component of vitamin B5 and thereby is essential for Coenzyme A function, but also contributes to plant responses to both biotic and abiotic stresses." (Jander et al.,2020)

D-Amino acids

"D-Amino acid isomers of the proteinogenic L-amino acids are produced by soil microbes and are taken up by plant roots, but can also be produced by plants themselves (Genchi, 2017)." (Jander et al.,2020)

Canavanine

"Canavanine is common in the tribes Galegeae, Loteae, Tephrosieae, Robinieae and some Phaseoleae. It could be assumed that the trait of canavanine accumulation was acquired by an ancestor... from which all the other tribes derived, but that the canavanine genes are turned off in Vicieae, Trifolieae, Cicereae and Abreae which produce pipecolic acids instead." [Acamovie PPRT]

Lathyrogens

Lathyrogens are a specific subset of NPAAs. "Lathyrogens, amino acids found mainly in the seeds of sweetpea (Lathyrus odoratus) and its relatives (Lathyrus spp., Vicia spp.), are responsible for lathyrism, a chronic disease. [CPPlantMush] They are 'any of a group of nucleophilic compounds (as B-aminopropionitrile) that tend to cause lathyrism and inhibit the formation of links between chains of collagen'." [merriam-webster]

Common Sources:

  • Lathyrus sativus (Grass Pea/Chickling Vetch) [Rosenthal HerbV1]
  • Lathyrus sylvestris [Rosenthal HerbV1]
  • Lathyrus cicera (Flat-podded Vetch) [Rosenthal HerbV1]
  • Lathyrus latifolius [Rosenthal HerbV1]
  • Lathyrus clymenum (Spanish Vetchling) [Rosenthal HerbV1]

1. Neurolathyrism

"The extensive literature existing on 'lathyrogens' mostly refer to a group of synthetic compounds inducing skeletal deformities... Human lathyrism bears no resemblance to these defects and is actually characterized by spastic paralysis of the legs as a result of neurological lesions of the spinal cord degeneration." [Liener TCPF]

"While osteolathyrism as such is not a public health problem, neurolathyrism is... A 1958 epidemiological survey... indicates that in a single District... there are as many as 25,000 cases of neurolathyrism in a total population of 634,000. The L. sativus is a hardy crop... thus forming a major portion of the diet especially under famine conditions." [Liener TCPF]

"Lathyrogen toxin is one of the natural toxins found in the seeds of lathyrus... known to cause lathyrism." (Amit et al, 2009)

"If consumed in excess quantity for long time, it causes paralysis in the legs... believed to be caused by a toxic amino acid known as N-Oxalyl amino alanine (BOAA). The BOAA content of seed of lathyrus varies from 0.05 to 0.4%... Less than 0.2% BOAA is considered safer from health point of view." (Amit et al, 2009)

Processing & Detoxification:

"The concentration of BOAA is maximum in the germ portion of the seed... therefore the degerming of the seed cotyledons greatly reduces the neurotoxin content... Processing techniques like soaking, parboiling, roasting and degerming eliminates neurotoxin to a large extent. Pre-cooking soaking of pulse removes 30-40% of toxin... Roasting of seeds for about 15-20 min at 140°C removes most of the toxin... Preboiling of lathyrus seeds removes more than 80% of the toxin." (Amit et al, 2009)

2. Osteolathyrism

"Certain members of the Lathyrus and Vicia genera contain compounds called osteolathyrogens which are teratogenic, causing congenital skeletal defects in offspring... The natural lathyrogen believed to be the teratogen is B-aminopropionitrile." [Riet-Correa PPMRT]

"Another malady distinct clinically from neurolathyrism is osteolathyrism; the latter involves bone and mesenchymal tissue aberrations... Animals eating Lathyrus odoratus seeds exhibit osteolathyritic effects... Lathyrus species such as L. hirsutus and L. pusillus give rise to both neurolathyritic and osteolathyritic effects, but L. odoratus induces only osteolathyrism." [Rosenthal HerbV1]

Methods of Detection:

"Since the lathyrogens occurring in nature happen to be amino acids or their derivatives, ninhydrin reagent can be used for their detection and estimation. β-Aminopropionitrile gives a characteristic green color with ninhydrin... β-cyanoalanine also gives a green color." [Liener TCPF]

References (NPAAs)

  • Amit et al, 2009 - Jain, Amit Kumar, Sudhir Kumar Sudhir Kumar, and J. D. S. Panwar. "Antinutritional factors and their detoxification in pulses-a review." (2009): 64-70.
  • Fichtner et al.,2017 - Fichtner, Maximilian, Kerstin Voigt, and Stefan Schuster. "The tip and hidden part of the iceberg: Proteinogenic and non-proteinogenic aliphatic amino acids." Biochimica et Biophysica Acta (BBA)-General Subjects 1861.1 (2017): 3258-3269.
  • Jander et al.,2020 - Jander, Georg, et al. "Physiological aspects of non-proteinogenic amino acids in plants." Frontiers in Plant Science 11 (2020): 5464.
  • Kasperkiewicz et al.,2012 - Kasperkiewicz, Paulina, Anna D. Gajda, and Marcin Drąg. "Current and prospective applications of non-proteinogenic amino acids in profiling of proteases substrate specificity." Biological chemistry 393.9 (2012): 843-851.

Lectins

Carbohydrate-recognizing proteins. "Though there is no doubt that some lectins are potent toxins (e.g., ricin, abrin), toxicity is the exception rather than the rule." Some show antifungal activity.

Peptides

Overview

"Polypeptides refer to the compounds formed by connecting α-amino acids through peptide bonds, generally composed of less than 100 amino acids, and are divided into natural polypeptides and proteolytic polypeptides." [Wang, Wenqi, et al., 2022]

Chemical structure of a polypeptide chain with arrows pointing to the peptide bonds between amino acid residues.
Figure 1. Structure of a Polypeptide Chain. This diagram shows a series of amino acids linked together to form a polypeptide. The arrows specifically highlight the peptide bonds—the covalent amide linkages formed between the carboxyl group (C=O) of one amino acid and the amino group (N-H) of the next. The 'R' groups (R1, R2, etc.) represent the variable side chains of each amino acid.

"Plant polypeptides are small molecule polypeptides formed by hydrolysis of plant proteins under specific conditions. Common plant polypeptides include oligopeptides, cyclic peptides, cyclic peptide alkaloids, glycopeptides, etc. [1]." [Wang, Wenqi, et al., 2022]

"Bioactive peptides can be endogenous or exogenous. Exogenous bioactive peptides are sequences of amino acids 2–30 in length that are inactive within the parent protein source but are released through the action of proteolytic enzymes during fermentation, hydrolysis, and food processing. These exogenous bioactive peptides have health benefits that go above and beyond basic, human nutrition and they exert “hormone-like beneficial activities” in the consumer if taken in relevant quantities and if they survive breakdown by proteolytic enzymes present in the gastrointestinal tract. Plant-derived bioactive peptides are thought to be a source of health-enhancing compounds and are consumed as part of a healthy, balanced diet." [Hayes&Bleakley.,2018]

Polypeptide Signaling

"Polypeptide signaling is an emerging field in plant biology, particularly in areas of defense, fertilization, growth, and development. Until 1991, polypeptide hormones and pheromones were thought to be only found in animals and yeast, and it was thought that plants had evolved signaling systems that did not include polypeptide signals. Following the initial discovery in 1991 of the 18-amino acid polypeptide defense hormone systemin and its precursor prosystemin in tomato leaves (6, 9), several plant polypeptide signals have been isolated and characterized or else identified by gene tagging (3, 5, 13, 15)." [Clarence&Pearce,2001]

"Because of the low abundance of polypeptide hormones in tissues and organs of animals and plants, their isolations have been typically time consuming and difficult." [Clarence&Pearce,2001]

Systemins

"The initial polypeptide signal that was identified in plants, systemin, was found in our laboratory during a search for the chemical agent that was responsible for the systemic induction of proteinase inhibitors in tomato leaves. We had found that fractions from crude extracts obtained from tomato leaves activated proteinase inhibitor genes when supplied to young excised tomato plants through their cut stems. We identified the active components as oligogalacturonide fragments derived from plant cell walls." It was "found that oligogalacturonides could activate the synthesis of phytoalexins, which are defense chemicals in soybeans and castor beans. Further research revealed that the oligogalacturonides were not mobile in tomato plants and were therefore not likely candidates for systemic signaling, but are localized signals to help defend against pest and pathogen attacks." [Clarence&Pearce,2001]

"Systemin is the only polypeptide ligand in plants for which a receptor has been identified and isolated, for which the elements of a signal transduction pathway are known, and for which several genes regulated by the polypeptide have been identified." [Clarence&Pearce,2001]

"Genes coding for systemins have been identified in potato, pepper, and nightshade, but not in tobacco, a more distantly related solanaceous species (2). Tobacco plants also did not respond to tomato systemin, although wounding caused a systemic activation of the synthesis of proteinase inhibitors in tobacco leaves. This wound response utilizes the octadecanoid pathway, similar to wound signaling in tomato plants, with methyl jasmonate being a potent inducer of the defense genes. In searching for the systemic signal in tobacco leaves two 18-amino acid tobacco systemins were recently isolated... that exhibit no homology to tomato systemin." [Clarence&Pearce,2001]

"Despite structural differences among the polypeptide defense signals, we propose that plant-derived polypeptides that signal defense genes, locally or systemically, be called systemins. The data so far indicate that systemins and their receptors may be a common feature of plants, but that structurally different systemin polypeptides may serve the same functions in different plant species. Systemins homologous to tomato or tobacco systemins have not been found in species outside the Solanaceae family, but searches for their presence in other species continue." [Clarence&Pearce,2001]

Signaling Peptides Found in:

  • Systemin - Tomato, potato, pepper and nighshade leaves [Clarence&Pearce,2001]
  • Systemins - Tobacco leaves [Clarence&Pearce,2001]
  • ENOD40 - Tobacco, alfalfa, pea, soybean, vetch [Clarence&Pearce,2001]
  • CLAVATA3 - Arabidopsis meristems [Clarence&Pearce,2001]
  • SCR - Brassica pollen [Clarence&Pearce,2001]
  • PSK
  • RALF

Structural Categories & Case Studies

Cyclopolypeptides

"Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process." [Dahiya, Rajiv, et al.,2021]

Oligopeptides

"An oligopeptide, often just called peptide (oligo-, "a few"), consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides." [1-Wiki]

Notable Oligopeptides:

  • Amanitins: "Cyclic peptides taken from carpophores of several different mushroom species. They are potent inhibitors of RNA polymerases in most eukaryotic species, the prevent the production of mRNA and protein synthesis. These peptides are important in the study of transcription. Alpha-amanitin is the main toxin from the species Amanita phalloides, poisonous if ingested by humans or animals." [4-Wiki]
    • [Image of Alpha-amanitin chemical structure]
  • Phalloidin: "A very toxic polypeptide isolated mainly from Amanita phalloides (Agaricaceae) or death cap; causes fatal liver, kidney and CNS damage in mushroom poisoning; used in the study of liver damage." [4-Wiki]
  • Antipain
  • Glutathione
  • Pepstatins

Aloe Sp. Polypeptides

"Results of the separation electrophoresis analysis of extracts prepared from fresh whole leaves and leaf gel of mature Aloe barbadensis Miller plants revealed 23 identifiable different polypeptides. Molecular weights of these polypeptides, calculated from sets of molecular weight reference standards, ranged from 70 000 for the largest to 3000 for the smallest. Electrophoresis profiles of commercially processed and freshly processed Aloe barbadensis Miller and Aloe saponaria Haw leaf gel extracts revealed similar patterns for major peptides. Treatment of mature whole Aloe leaf extracts with acidic and alkaline conditions revealed distinct changes in pH stability of ten peptides. Comparisons of separation electrophoresis profiles of fresh extracts of Aloe whole leaves and of leaf gel portions revealed marked differences in both molecular weights and concentrations of peptides found in extracts from mature, young or immature plants. This report is the first to describe the nature and types of polypeptides detected in extracts of whole leaf, leaf gel, stalk and root portions of immature, young and mature Aloe plants." [Winters et al.,1995]

Antimicrobial Peptides (AMPs)

"Plants produce antimicrobial peptides (AMPs) to defend themselves against pathogens." [López-García et al.,2012] "As part of their defensive arsenal, they use antimicrobial peptides such as thionins, defensins, lipid transfer proteins, hevein-like peptides, knottins, cyclotides, ß-barrelins, and others." [Villa AC] The repertoire of AMPs synthesized by plants is extremely large, with hundreds of different AMPs in some plant species. In spite of their molecular diversity most plant AMPs share common features: they are basic, amphypatic and cysteine-rich peptides with a stabilized structure by disulfide bonds. Plant AMPs antimicrobial activity is not only against plant pathogens and predatory insects, but also against human viruses, bacteria, fungi, protozoa parasites and neoplastic cells." [López-García et al.,2012]

[Image of Plant antimicrobial peptide mechanism of action against pathogens]

"Antimicrobial peptides (AMPs) are ubiquitous and found as host defenses against pathogens and pests in diverse organisms ranging from microbes to animals [5]. AMPs exist in different molecular forms, although the majority of them are linear peptides from insects, animals, and plants. Nevertheless, bacteria produce polycyclic peptides such as lantibiotics, and all major forms of life produce circular peptides which include bacteriocins from bacteria, cyclotides from plants and theta-defensins from animals [6,7,8,9]. In plants, the majority of AMPs are Cys-rich [10], a feature that enables the formation of multiple disulfide bonds (usually two to six) that contribute to a compact structure and resistance to chemical and proteolytic degradation." [Tam et al.,2015]

See also:

  • defensin
  • α-hairpinin
  • snakin

Thionins

"Thionins have been identified from monocots and dicots and are expressed in different tissues, such as seeds, leaves, and roots [35,36,37]. The expression of thionins can be induced by infection with various microbes [38,39] and has been shown to be related to the release of the hormone methyl jasmonate upon plant wounding or microorganism invasion [38,40,41]. Thionins are ribosomally derived and expressed as preproproteins, wherein the prothionin domain is flanked by two conserved sequences, the N-terminal signaling peptide and C-terminal acidic domain [35,38,42]. Mature thionin sequences display more variation than the conserved terminal domains in the preproprotein due to evolutionary pressure [43]. The three-domain precursor of plant AMPs in CRP families is typical and found in other CRP families, including defensins, hevein-like peptides, and knottin-type peptides." [Tam et al.,2015]

Knottins

"Knottins can be found in plants, animal, and fungi and they have toxic, inhibitory, and regulatory functions." [Villa AC]

"Knottin is a generic term for small proteins with a particular type of cysteine knot motif known as inhibitor cysteine knot (Isaacs 1995). Cysteine knots require two disulfide bridges that form a circular structure with the protein backbone. The knot is formed when a third disulfide bridge crosses this circular structure. In the case of inhibitor cysteine knots, this third bridge is the one formed by cysteines III and VI". [Villa AC]

Found in:

  • Mirabilis jalapa (Seeds) [Villa AC]
  • Phytolacca americana [Villa AC]

ß-barrelins

"The ß-barrelin or MiAMP1 family is present in gymnosperms, angiosperms, and spikemosses, although they seem to be missing in several species with sequenced genomes (Manners 2009)." [Villa AC]

"The ß-barrelin precursor proteins have a signal peptide and in gymnosperms expression is induced by fungal attack, supporting an in vivo defensive role (Manners 2009; Sooriyaarachchi et al. 2011)." [Villa AC]

"The family has been named ß-barrelins due to the three-dimensional structure of MiAMP1 [a peptide purified from macadamia nuts]. This protein, which is 76 amino acids long, forms a barrel of eight ß-strands that includes three disulfide bonds (McManus et al. 1999). Sequence conservation is high in the family and basic amino acids are abundant." [Villa AC]

"The mechanism of action of these peptides against fungi appears to involve binding specifically to ß-(1,3)-glucans in fungal cell walls through conserved polar and aromatic residues (Sooriyaarachchi et al. 2011). The three-dimensional structure of ß-barrelins is very similar to that of the fungal killer toxin HM-1, which interacts with ß-(1,3)-glucans and blocks their synthesis (Kasahara et al. 1994; McManus et al. 1999)." [Villa AC]

Found in:

  • macadamia [Villa AC]
  • pine [Villa AC]

References

  • [Dahiya, Rajiv, et al.,2021] Dahiya, Rajiv, et al. "Natural cyclic polypeptides as vital phytochemical constituents from seeds of selected medicinal plants." Archiv der Pharmazie 354.4 (2021): 2000446.
  • [Hayes&Bleakley.,2018] Hayes, Maria, and Stephen Bleakley. "Peptides from plants and their applications." Peptide applications in biomedicine, biotechnology and bioengineering. Woodhead Publishing, 2018. 603-622.
  • [López-García et al.,2012] López-García, Belén, Blanca San Segundo, and María Coca. "Antimicrobial peptides as a promising alternative for plant disease protection." Small wonders: peptides for disease control (2012): 263-294.
  • [Clarence&Pearce,2001] Ryan, Clarence A., and Gregory Pearce. "Polypeptide hormones." Plant Physiology 125.1 (2001): 65-68.
  • [Tam et al.,2015] Tam, James P., et al. "Antimicrobial peptides from plants." Pharmaceuticals 8.4 (2015): 711-757.
  • [Wang, Wenqi, et al., 2022] Wang, Wenqi, et al. "Plant polypeptides: A review on extraction, isolation, bioactivities and prospects." International Journal of Biological Macromolecules 207 (2022): 169-178.
  • Wiki - Oligopeptide, https://en.wikipedia.org/wiki/Oligopeptide, This page was last edited on 18 December 2019, at 02:04 (UTC)., Accessed March 4, 2020
    • [2], George E. Chlipala, Shunyan Mo, and Jimmy Orjala (2011). "Chemodiversity in Freshwater and Terrestrial Cyanobacteria – a Source for Drug Discovery". Curr Drug Targets. 12 (11): 1654–73. doi:10.2174/138945011798109455. PMC 3244969. PMID 21561419
    • [4], Argos, Patrick. "An Investigation of Oligopeptides Linking Domains in Protein Tertiary Structures and Possible Candidates for General Gene Fusion" (PDF). European Molecular Biology Laboratory. Archived from the original (PDF) on 28 July 2014. Retrieved 28 July 2014.
  • [Winters et al.,1995] Winters, Wendell D., and Catherine Bouthet. "Polypeptides of Aloe barbadensis miller." Phytotherapy Research 9.6 (1995): 395-400.

Thiaminases

Class: Enzyme

Enzymes that metabolize or destroy Thiamine (Vitamin B1). Found in Bracken Fern and Horsetail. Ingestion can cause Vitamin B1 deficiency (Beriberi) in animals. Full profile.

Oxalates

Class: Organic Acid

Found in Sorrel (Rumex) and Rhubarb. Soluble oxalates bind calcium; insoluble crystals (raphides) cause mechanical irritation. Full profile.