No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Presence of L-Canavanine in Hedysarum alpinum Seeds and Its Potential Role in the Death of Chris McCandless
Abstract
For the past 2 decades there has been vigorous disagreement over the purported toxicity of Hedysarum alpinum seeds, and whether the consumption of such seeds was a factor in the 1992 death of Chris McCandless, the subject of the book Into the Wild. Our objective was to confirm or disprove the presence of L-canavanine (a nonprotein amino acid known to induce systemic lupuslike symptoms in humans) in H alpinum seeds.
Liquid chromatography-tandem mass spectrometry analysis of H alpinum seeds was performed.
Our analysis confirmed the presence of L-canavanine in H alpinum seeds and demonstrated that it is a significant component of the seeds, with a concentration of 1.2% (weight/weight), roughly half of that found in Canavalia ensiformis.
The data led us to conclude it is highly likely that the consumption of H alpinum seeds contributed to the death of Chris McCandless.
Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
... Papilionoideae (Rosenthal, 1977;Fowden, 1980;Rosenthal, 2001;Krakauer et al., 2015) Djenkolic acid Nephrotoxicity Archidendron pauciflorum (Nunn et al., 2010) D-or L-p-hydroxyphenyl-Gly N/A N/A (Walsh et al., 2013) 3,4-dichloro-L-proline N/A Penicillium islandicum ) DL-p-FPhe, DL-m-FPhe, DL-o-FPhe Antibacterial activity Unnatural synthesis (Krátký et al., 2017) Ethanolamine N/A N/A (Hatanaka, 1992) Ethynylpyrrolysine N/A Unnatural synthesis (Ehrlich et al., 2015) 4-methyl-L-proline N/A Cyanobacteria; Nostoc sp. GSV224 3-fluoro-L-tyrosine Probe catalytic mechanism of aspartate aminotransferase N/A (Park et al., 1997) 2-fluorotyrosine, 2,3-difluorotyrosine N/A N/A (Books et al., 1998) Hydroxylysine, Hydroxyproline Urinary diagnostic reagents for chronic liver disease ...
... Other plant-derived ncAAs counter animal threats. L-canavanine, which is found in the legume Papilionoideae, can cause muscle palsy and can induce systemic lupus erythematosus (Rosenthal, 1977;Rosenthal, 2001;Krakauer et al., 2015) (Table 1). The imino acid azetidine-2-carboxylic acid is an analog of the coding amino acid L-proline and is incorporated during the synthesis of human immune-related proteins; this ncAA has been associated with neuropathies and multiple sclerosis (Rubenstein, 2008). ...
Compared with the better-studied canonical amino acids, the distribution, metabolism and functions of natural non-canonical amino acids remain relatively obscure. Natural non-canonical amino acids have been mainly discovered in plants as secondary metabolites that perform diversified physiological functions. Due to their specific characteristics, a broader range of natural and artificial non-canonical amino acids have recently been applied in the development of functional materials and pharmaceutical products. With the rapid development of advanced methods in biotechnology, non-canonical amino acids can be incorporated into peptides, proteins and enzymes to improve the function and performance relative to their natural counterparts. Therefore, biotechnological application of non-canonical amino acids in artificial bio-macromolecules follows the central goal of synthetic biology to: create novel life forms and functions. However, many of the non-canonical amino acids are synthesized via chemo- or semi-synthetic methods, and few non-canonical amino acids can be synthesized using natural in vivo pathways. Therefore, further research is needed to clarify the metabolic pathways and key enzymes of the non-canonical amino acids. This will lead to the discovery of more candidate non-canonical amino acids, especially for those that are derived from microorganisms and are naturally bio-compatible with chassis strains for in vivo biosynthesis. In this review, we summarize representative natural and artificial non-canonical amino acids, their known information regarding associated metabolic pathways, their characteristics and their practical applications. Moreover, this review summarizes current barriers in developing in vivo pathways for the synthesis of non-canonical amino acids, as well as other considerations, future trends and potential applications of non-canonical amino acids in advanced biotechnology.
... The toxicity of these products may be due to the fact that they replace coding analogues during protein synthesis. Examples include: azetidine-2-carboxylic acid (Aze), a proline analogue [37,38]; glufosinate, a glutamate analogue that is also a popular herbicide [39]; β-N-methylamino-L-alanine (BMAA), an analogue of serine [40]; and L-canavanine, a natural analogue of L-arginine that is exploited as an insecticide [41,42]. A remarkable true-life story involving a 119-day Alaskan wilderness experiment conducted by Christopher McCandless was recounted in the book Into the Wild by Jon Krakauer (later made into a popular movie) [43]. ...
... McCandless was thought to have died in the wilderness from starvation; however, Krakauer always suspected a toxin in the seeds of the wild potato, Hedysarum alpinum, which formed a staple of his diet in his last month of life. Krakauer had originally suspected a poisonous alkaloid but, through later research, was able to identify a significant level of L-canavanine in the wild potato seeds and published a paper on this analysis with several other authors in 2016 [42]. ...
Usage of the herbicide glyphosate on core crops in the USA has increased exponentially over the past two decades, in step with the exponential increase in autoimmune diseases including autism, multiple sclerosis, inflammatory bowel disease, type 1 diabetes, coeliac disease, neuromyelitis optica and many others. In this paper we explain how glyphosate, acting as a non-coding amino acid analogue of glycine, could erroneously be integrated with or incorporated into protein synthesis in place of glycine, producing a defective product that resists proteolysis. Whether produced by a microbe or present in a food source, such a peptide could lead to autoimmune disease through molecular mimicry. We discuss similarities in other naturally produced disease-causing amino acid analogues, such as the herbicide glufosinate and the insecticide L-canavanine, and provide multiple examples of glycine-containing short peptides linked to autoimmune disease, particularly with respect to multiple sclerosis. Most disturbing is the presence of glyphosate in many popular vaccines including the measles, mumps and rubella (MMR) vaccine, which we have verified here for the first time. Contamination may come through bovine protein, bovine calf serum, bovine casein, egg protein and/or gelatin. Gelatin sourced from the skin and bones of pigs and cattle given glyphosate-contaminated feed contains the herbicide. Collagen, the principal component of gelatin, contains very high levels of glycine, as do the digestive enzymes: pepsin, trypsin and lipase. The live measles virus could produce glyphosate-containing haemagglutinin, which might induce an autoimmune attack on myelin basic protein, commonly observed in autism. Regulatory agencies urgently need to reconsider the risks associated with the indiscriminate use of glyphosate to control weeds.
... The rate of replacement may be increased in the presence of inflammation or other conditions that can lead to arginine deficiency [42]. Notably, consumption of canavanine containing seeds from Hedysarum alpinum is believed to have contributed to the death of Chris McCandless, the subject of the book Into the Wild [43]. Members of the genus Canavalia (e.g., Canavalia ensiformis; jack bean) accumulate canavanine in high concentrations, as does alfalfa or lucerne (Medicago sativa) to a lesser extent. ...
Global food production relies on annual grain crops. The reliability and productivity of these crops are threatened by adaptations to climate change and unsustainable rates of soil loss associated with their cultivation. Perennial grain crops, which do not require planting every year, have been proposed as a transformative solution to these challenges. Perennial grain crops typically rely on wild species as direct domesticates or as sources of perenniality in hybridization with annual grains. Onobrychis spp. (sainfoins) are a genus of perennial legumes domesticated as ancient forages. Baki™ bean is the tradename for pulses derived from sainfoins, with ongoing domestication underway to extend demonstrated benefits to sustainable agriculture. This study contributes to a growing body of evidence characterizing the nutritional quality of Baki™ bean. Through two studies, we investigated the safety of Baki™ bean for human consumption. We quantified heavy metals, folate, and canavanine for samples from commercial seed producers, and we quantified levels of mycotoxins, microorganisms, and pesticides in samples from a single year and seed producer, representing different varieties and production locations. The investigated analytes were not detectable or occurred at levels that do not pose a significant safety risk. Overall, this study supports the safety of Baki™ bean for human consumption as a novel pulse crop.
... He encountered impassable conditions and died in August of 1992 due to malnourishment. A recent article (Krakauer et al., 2015) concluded that consumption of H alpinum (wild potato) seeds contributed to his death. ...
In late spring of 1992, Christopher McCandless crossed the Teklanika River, west of Healy, Alaska (United States). His summer has been well documented both in the book and the movie ‘Into the Wild.’ In early summer of 1992, he attempted to cross back over the river, but was stopped by high waters and he died later that summer. This paper investigates the hydrologic conditions of the Teklanika River watershed. We consider both climatological conditions and also conditions during the summer of 1992. We run process-based snowpack and runoff models in order to estimate the river hydrograph at the point of Mr. McCandless’ attempted crossing. Our results demonstrate that the Teklanika river is very flashy during the summer, responding rapidly to strong episodic rainfall events. The main snowmelt signal occurred in mid-to-late May, after Mr. McCandless’ first crossing and before his second attempt. The specific day of his attempted re-crossing corresponded to a large runoff event, driven by rainfall. We conclude that Mr. McCandless had unfortunate timing and that, had he tried to cross a day or two earlier or later, the outcome may have been different. This paper is also an opportunity to explore the hydrologic compromises that must be made when trying to study ungauged, or poorly gauged, areas. There is a spectrum of choices regarding input datasets and methodological simplifications and the correct location on that spectrum will depend on the particular watershed the objectives and expectations of the study.
... Фармакологическим потенциалом обладают не только взрослые и полностью сформированные растения. В работе группы ученых (Jon Krakauer, Ying Long, Andrew Kolbert и др., 2015 г.) было установлено, что в семенах H. alpinum в достаточной концентрации содержится L-канаванин, который способен спровоцировать смерть человека [12]. Подобный случай произошел в 1992 г. на Аляске, когда Кристофер Маккэндлесс, зная о том, что корни H. alpinum съедобны, употребил в пищу семена этого растения, после чего скончался. ...
Hedysarum gmelinii is a perspective species for the introduction into the culture and further use in the agricultural industry and pharmacology. The purpose of this research is to find suitable medium for seed germination. At present, this species is under the threat of extinction in several subjects of the Russian Federation. That is why research of the optimal nutrient medium for the seeds of H. gmeliniiis very relevant. Materials and methods: 100 pcs of mature seeds were selected from the populations of Tatarstan and Bashkortostan. The seed material had been stored at the 4°C before it was used. The Murashige and Skoog (MS) medium was prepared under the protocol with adding of such plant hormones like 6-benzylaminopurine (BAP) and Indole-3-acetic acid (IAA) in four types of concentrations. After that the sterilized seeds were planted. The germination was occurred at 20 °С and the daylight was 16 hours. The results: seeds started to grow up to 15th day of an experiment. Then the plants were transferred on the fresh medium. Young plants were formed after 13 days. Plants which seeds had been taken in Tatarstan showed the most active callus formation. Thus, the originality of this research is that the optimal medium for growing seeds of Hedysarum gmelinii in vitro was found. This medium ensures good viability and gives the opportunity to get the tissues culture for the further studies of the biologically active substances.
... While it was first thought he starved to death, it was later proposed ( Krakauer et al. 2015) that McCandless first became paralyzed from consuming L-canavanine via the potato seeds, and subsequently was unable to forage for food. Speculation on the nature of the interaction of BMAA with proteins was first presented by Murch et al. (2004) when they proposed a mechanism for the liberation of BMAA from the protein fraction of cycad flour following acid hydrolysis. ...
The size and frequency of cyanobacterial blooms are increasing concomitantly with rising global temperatures and increased eutrophication, and this has implications for human health. Cyanotoxins, including L-BMAA, have been implicated in triggering neurodegenerative diseases such as ALS/PDC and Alzheimer’s disease. L-BMAA is a water-soluble non-protein amino acid that can bioaccumulate up the food chain, in a free- and protein-bound form. While some data exists on the degree of environmental enrichment of L-BMAA in water bodies, cyanobacteria-derived supplements, fruit bats, and seafood, virtually nothing is known about the presence of L-BMAA in other foodstuffs. It has now been shown several times in laboratory settings that plants can absorb L-BMAA into their leaves and stems, but data from wild-grown plants is nascent. One of the mechanisms implicated in L-BMAA bioaccumulation is misincorporation into proteins in the place of the canonical amino acid L-serine. We first identified this as a mechanism of action of L-BMAA in 2013, and since then, several groups have replicated these findings, but others have not. Here, we discuss in detail the experimental approaches, why they may have produced negative findings and propose several ways forward for developing consistency within the field. We emphasize the need to standardize cell culture methods, using L-serine-free medium to study misincorporation of BMAA, and urge accurate reporting of the components present in cell culture media.
... Researchers have suggested that m-tyrosine may be useful as a natural herbicide in crop management [77]. Other examples include Azetidine-2-carboxylic acid (Aze), an analogue of proline [78], β-Methylamino-l-alanine (BMAA), an analogue of serine [79,80], and L-canavanine, an amino acid analogue of arginine [81]. All of these amino acid analogues cause serious diseases, often with a long latency period, through the disruption of protein function of a diverse number of proteins. ...
Chronic kidney disease of unknown etiology (CKDu) is a global epidemic. Sri Lanka has experienced a doubling of the disease every 4 or 5 years since it was first identified in the North Central province in the mid-1990s. The disease primarily affects people in agricultural regions who are missing the commonly known risk factors for CKD. Sri Lanka is not alone: health workers have reported prevalence of CKDu in Mexico, Nicaragua, El Salvador, and the state of Andhra Pradesh in India. A global search for the cause of CKDu has not identified a single factor, but rather many factors that may contribute to the etiology of the disease. Some of these factors include heat stroke leading to dehydration, toxic metals such as cadmium and arsenic, fluoride, low selenium, toxigenic cyanobacteria, nutritionally deficient diet and mycotoxins from mold exposure. Furthermore, exposure to agrichemicals, particularly glyphosate and paraquat, are likely compounding factors, and may be the primary factors. Here, we argue that glyphosate in particular is working synergistically with most of the other factors to increase toxic effects. We propose, further, that glyphosate causes insidious harm through its action as an amino acid analogue of glycine, and that this interferes with natural protective mechanisms against other exposures. Glyphosate’s synergistic health effects in combination with exposure to other pollutants, in particular paraquat, and physical labor in the ubiquitous high temperatures of lowland tropical regions, could result in renal damage consistent with CKDu in Sri Lanka.
... CAN has been found in leaves of balloon pea [Sutherlandia frucescens (L.) R.Br.], a plant often used in alternative medicine, especially in southern Africa (Colling et al. 2010). Its presence in ''alpine sweet vetch'' (Hedysarum alpinum L.) seed, consumed by Christopher McCandless, an American hiker and itinerant traveler, likely constituted a contributing factor to his death (Krakauer et al. 2015). Consumption of sprouts and seed of lucerne (Medicago sativa L.) containing CAN are suggested to be associated with the development of an autoimmune disease-systemic lupus erythematosus observed e.g. in monkeys (Malinow et al. 1982). ...
l-Canavanine (CAN) is a non-protein amino acid (NPAA) possessing toxic properties in both animal and plant systems. Upon treatment, this arginine structural analogue is typically incorporated into proteins by arginyl-tRNA synthetase, leading to rapid functional disruption of such “canavanyl proteins”. CAN is produced in many legumes including jack bean and lucerne (alfalfa) and is accumulated mainly in seeds and their newly germinating sprouts. It has been described as a potent allelochemical and its toxicity has been associated with autoimmunological diseases in humans or animals feeding on plants containing this NPAA. Application of CAN even at low concentration resulted in an inhibition of plant growth. When CAN was used as an anticancer agent, its mode of action appears to be associated with the synthesis of non-functional proteins in sensitive organisms, a similar mode of action to that of other simple NPAAs as meta-tyrosine. CAN toxicity in plants is also likely associated with the formation of non-functional proteins and its application has been shown to cause disruption of polyamine metabolism and formation of reactive nitrogen species including nitric oxide (NO). In higher plants, CAN has recently been used as a tool to study the regulation or modulation of polyamine–NO cross-talk. Comparing to other related NPAAs that impact cellular function in living plant and animal systems CAN seems to have the highest toxic properties. The aim of this review is to describe CAN specific activity and mode of action especially focused on higher plant systems.
... A diet of wild potato seeds containing L-canavanine could have resulted in muscle paralysis and the eventual death of Christopher McCandless, wilderness explorer and inspiration for the film "Into the Wild" (Krakauer et al. 2015). L-Canavanine, if supplied in high enough concentrations, is lethal to rats due to its ability to replace L-arginine in protein synthesis (Thomas and Rosenthal 1987). ...
The 20 DNA-coded protein amino acids play central roles in the metabolism of most organisms. As well as being the building blocks for proteins, they play essential roles in a diverse range of metabolic pathways. They are estimated to be around 1000 molecules in nature, which share the same basic structure as these organic amino acids consisting of an α-carbon attached to a carboxyl group, an amino group, a hydrogen atom, and a unique side-chain group. Many “nonprotein” amino acids (NPAAs) are plant secondary metabolites.
In this chapter, the authors discuss plant NPAAs that have a similar chemical structure, size, shape, and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, overstimulate receptors, or chelate metal ions. Most often this results in some level of toxicity to the target organism and can confer some advantage to the plant. Toxic NPAAs might have evolved as defense chemicals that can be released into the soil to inhibit the growth of other plants or agents that can limit insect herbivory.
The effects of NPAAs on human health are not well understood. Consumption of a number of plants that contain NPAAs has been shown to have acutely toxic effects in humans. The key questions that remain unanswered are to what extent can NPAAs enter the food chain and what are the effects of a chronic low-level exposure to toxic plant NPAAs?
... These polypeptides actually aggregate and accumulate in plaque regions also containing TDP-43 and FUS. It may be significant that all three of these amino acids have naturally occurring analogues that cause disease, as explained in the associated references provided in the table [212][213][214] . It seems plausible that the process that incorporates these amino acids in high concentrations into peptides that are removed from circulation may be a strategy to try to expunge the offending analogues from the cytoplasm. ...
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease involving several protein mutations in glycine-rich regions with limited treatment options. 90-95% of all cases are non-familial with epidemiological studies showing a significant increased risk in glyphosate-exposed workers. In this paper, we propose that glyphosate, the active ingredient in Roundup®, plays a role in ALS, mainly through mistakenly substituting for glycine during protein synthesis, disruption of mineral homeostasis as well as setting up a state of dysbiosis. Mouse models of ALS reveal a pre-symptomatic profile of gut dysbiosis. This dysbiotic state initiate a cascade of events initially impairing metabolism in the gut, and, ultimately, through a series of intermediate stages, leading to motor neuron axonal damage seen in ALS. Lipopolysaccharide, a toxic by-product of dysbiosis which contributes to the pathology, is shown to be statistically higher in ALS patients. In this paper we paint a compelling view of how glyphosate exerts its deleterious effects, including mitochondrial stress and oxidative damage through glycine substitution. Furthermore, its mineral chelation properties disrupt manganese, copper and zinc balance, and it induces glutamate toxicity in the synapse, which results in a die-back phenomenon in axons of motor neurons supplying the damaged skeletal muscles. Citation: Seneff, S., et al. Does glyphosate acting as a glycine analogue contribute to ALS? (2016) J Bioinfo Proteomics Rev 2(3): 1-21. Seneff, S., et al.
... For example, a natural non-coding amino acid analogue of proline, azetidine-2-carboxylic acid (Aze), is linked to multiple sclerosis due to its ability to displace proline in peptides [14]. Similarly, L-canavanine, a natural non-coding analogue of L-arginine, is a toxin stored in the seeds of certain plants [15,16]. β-N-methylamino-L-alanine (BMAA), a natural analogue of serine synthesized by cyanobacteria, is implicated in amyotrophic lateral sclerosis (ALS) and other neurological diseases [1]. ...
Glyphosate, a synthetic amino acid and analogue of glycine, is the most widely used biocide
on the planet. Its presence in food for human consumption and animal feed is ubiquitous.
Epidemiological studies have revealed a strong correlation between the increasing incidence
in the United States of a large number of chronic diseases and the increased use of
glyphosate herbicide on corn, soy and wheat crops. Glyphosate, acting as a glycine
analogue, may be mistakenly incorporated into peptides during protein synthesis. A deep
search of the research literature has revealed a number of protein classes that depend on
conserved glycine residues for proper function. Glycine, the smallest amino acid, has unique
properties that support flexibility and the ability to anchor to the plasma membrane or the
cytoskeleton. Glyphosate substitution for conserved glycines can easily explain a link with
diabetes, obesity, asthma, chronic obstructive pulmonary disease (COPD), pulmonary
edema, adrenal insufficiency, hypothyroidism, Alzheimer’s disease, amyotrophic lateral
sclerosis (ALS), Parkinson’s disease, prion diseases, lupus, mitochondrial disease, non-
Hodgkin’s lymphoma, neural tube defects, infertility, hypertension, glaucoma, osteoporosis,
fatty liver disease and kidney failure. The correlation data together with the direct biological
evidence make a compelling case for glyphosate action as a glycine analogue to account for
much of glyphosate’s toxicity. Glufosinate, an analogue of glutamate, likely exhibits an
analogous toxicity mechanism. There is an urgent need to find an effective and economical
way to grow crops without the use of glyphosate and glufosinate as herbicides.
The plants of Hedysarum alpinum L. in the North are characterized by a long pregenerative period, the laboriousness of seed propagation, low field germination of seeds, rare self-sowing, and the impossibility of vegetative propagation. In connection with this, it seemed relevant to introduce this rare species (included in the Red Book of the Komi Republic) into aseptic culture to preserve and maintain the gene pool, as well as to further develop the technology of its cultivation to obtain medicinal raw materials. The morphogenesis was studied, and the peculiarities of the regeneration of adventitious shoots of Hedysarum alpinum in in vitro culture were revealed. During three subcultivations, the influence of two cytokinin growth regulators, 6-benzylaminopurine (BAP) and kinetin (KIN), at concentrations from 0,5 to 1,0 mg/l, on the regeneration potential of different explants of Hedysarum alpinum in in vitro culture was determined on the WPM environment. A high frequency of regeneration of shoots from single-node segments and cotyledon nodes was obtained 79% and 65%, respectively. In the second and third passages, there was an increase in the regenerative activity of the cotyledon node explants and an increase in the multiplication factor to 5 shoots per explant. It was shown that relatively high concentrations (1,0 mg/l) of BAP and CIN increase the number of shoots per explant but inhibit their growth and development. For the reproduction stage proper, the medium containing BAP 0,5 + CIN 0,5 + IAA 0,1 mg/l is optimal. It was shown that the initiation of rhizogenesis actively took place on the WPM medium supplemented with IAA 0,5 and IBA 0,5 mg/l, on which the proportion of rhizogene explants was 77%. The maximum values for the length and number of roots were obtained on the medium with IAA 1,0 mg/l and with the combined use of two auxins (IAA with IBA at 0,5 mg/l). The regenerated plants were transplanted into non-sterile conditions, and their survival rate under ex vitro conditions was 50%.
Many nonprotein amino acids (NPAAs) are plant secondary metabolites and have a similar chemical structure , size, shape and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, overstimulate receptors or chelate metal ions. The Consumption of a number of plants that contain NPAAs has been shown to have acutely toxic effects in humans. The consumption of some seeds or vegetables that contain NPAAs inuences some people as a trigger for some diseases or as an exacerbating factor. The effects of NPAAs on human health are not well understood. It has been observed that chimpanzees fed alfalfa and also a volunteer subject who have intake alfalfa tablets have both developed a disease with all the characteristics of lupus erythematosus ( an autoimmune disease) and by suppressing the consumption of alfalfa the disease disappears.
Most of NPAAs are of plant origin; these do not form part of the primary structure of proteins, they act as antimetabolites and most are found in higher plants; they have the same basic structure as amino acids of animal origin. The substitution of a protein amino acid in protein synthesis produces abnormal proteins which generate antibodies and modication of autoantigens as mechanism to break immunological tolerance and
trigger autoimmunity. Auto-antibodies formation is a characteristic of autoimmune disease. The toxic potential of NPAAs depend the amount ingested and the consumption time. Chronic exposure to NPAAs could contribute to autoimmune disease development in genetically susceptible individuals.
Christopher Mc Candless, an American adventurer who left to live in Alaska in the spring of 1992, died a few months later of extreme fatigue. Several hypotheses have been put forward to explain his death, the main one being poisoning by an endemic sainfoin, Hedysarum mackenziei Richardson, supposed to be toxic, and that he would have confused with another species, H. alpinum L., supposed not to be. Since the early 2000s, several studies have been published, putting forward other hypotheses, the most credible of which is that of a dramatic case of lathyrism.
The purpose. In order to increase soybean yield to develop the agent for pre-sowing seed treatment and crop spraying in the budding phase, and application of an agent for Round-up resistant soybean should reduce the synthesis of unnatural peptides with glycine glyphosate in the structure of proteins, which can cause unpredictable consequences for animals and humans. Methods. Laboratory and field experiments on chickens and hens. Results. The agent «Zernovit» for pre-sowing seed treatment of soybean seeds (patent of Ukraine for utility model No.119739, 2017) and in the budding phase has been developed. In addition, the formation of unnatural peptides of glycine glyphosate in the structure of proteins decreases through the stimulation of protein synthesis in the genetically modified soybean when applying «Zernovit». Conclusions. The agent «Zernovit» for pre-sowing soybean seed treatment and application in the budding phase, which provides an increase by 16.8 % in yields against the control of 2.8 t/ha, has been developed and tested in the conditions of production, and when it is used in genetically modified soybean it reduces the synthesis of unnatural peptides with glycine glyphosate in the structure of soybean protein when sprayed with Round-up. This is due to the stimulation of the protein synthesis that prevents the inclusion of glycine glyphosate in the unnatural peptides of the protein synthesis.
The 20 DNA-coded protein amino acids play central roles in the metabolism of most organisms. As well as being the building blocks for proteins, they play essential roles in a diverse range of metabolic pathways. They are estimated to be around 1000 molecules in nature, which share the same basic structure as these organic amino acids consisting of an α-carbon attached to a carboxyl group, an amino group, a hydrogen atom, and a unique side-chain group. Many “nonprotein” amino acids (NPAAs) are plant secondary metabolites.
In this chapter, the authors discuss plant NPAAs that have a similar chemical structure, size, shape, and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, overstimulate receptors, or chelate metal ions. Most often this results in some level of toxicity to the target organism and can confer some advantage to the plant. Toxic NPAAs might have evolved as defense chemicals that can be released into the soil to inhibit the growth of other plants or agents that can limit insect herbivory.
The effects of NPAAs on human health are not well understood. Consumption of a number of plants that contain NPAAs has been shown to have acutely toxic effects in humans. The key questions that remain unanswered are to what extent can NPAAs enter the food chain and what are the effects of a chronic low-level exposure to toxic plant NPAAs?
l-Canavanine, l-2-amino-4-(guanidinooxy)butyric acid, is a potentially toxic analogue of l-arginine. Canavanine-sensitive organisms activate and aminoacylate this non-protein amino acid and thereby create structurally aberrant, canavanine-containing proteins. Incorporation of canavanine into protein can alter the conformation and disrupt the function of the native macromolecule. Production of functionally impaired, canavanyl proteins affects developmental processes and contributes significantly to the expression of canavanine's potent antimetabolic properties in insects.
Many species of the dioecious, neo-tropical plant genus Clusia secrete a viscous, hydrophobic resin from glandular tissues in both male and female flowers. This substance is readily gathered
by meliponine and euglossine bees for whom it most often serves as the sole pollinator reward. Bees use Clusia resin as a nest-building material. As such, resin clearly serves an indispensable mechanical function. However, resins with
antimicrobial properties may also serve to reduce the risk of pathogenesis in the nest. If resin-gathering apids benefit from
antimicrobial properties in nesting materials and are able to discern these characteristics in the forage they gather, one
might predict that the resin reward presented in Clusia could have evolved under selection for both mechanical and antimicrobial properties. In dioecious species, where females
and males each present a resin reward, selection regimes may differ between the sexes with the result that resin form and
function diverge. We investigated both the form and function of the male and female pollinator reward resins of Clusia grandiflora. Using thin-layer chromatography (TLC), we compared the chemical compositions of floral resins from five widely separated
populations of this species growing in southeastern Venezuela. We found that male and female resins exhibited a marked chemical
dimorphism, with females having two major TLC-resolvable fractions and males having seven. This dimorphism was stable: there
were no component differences between populations in either sex. Using a disk-diffusion technique, we surveyed the same resins
for antimicrobial activity using assay microorganisms isolated from eusocial meliponine bees. Both male and female Clusia grandiflora resins had pronounced but relatively directed antimicrobial activity: both were toxic to 10 of 11 Gram-positive bacteria,
7 of 15 Gram-negative or variably-staining bacteria, 0 of 3 yeasts, and 0 of 3 filamentous fungi. Again with the disk-diffusion
technique, we performed more detailed tests of resin bioactivity using two Gram-positive honeybee associates, Paenibacillus larvae and P. alvei, as model pathogens. Both male and female C. grandiflora resins were highly toxic to these honeybee pathogens. Female resin, however, produced zones of inhibition with more than
twice the mean diameter of those produced by the male resin. This divergence in form and function of the C. grandiflora pollinator reward resins could be in response to different selective regimes as mediated by the pollinating insects.
The seeds of 161 species of legumes, representing 78 genera, were examined by chromatographic methods for canavanine content. The results are supplemented by data, variously collected, by other authors, to yield a total of 219 investigated species representing 109 genera. Of these, 68 species belonging to 32 genera have canavanine in their seeds.Canavanine has not been found in the subfamilies Mimosoideae or Caesalpinioideae. In the subfamily Papilionoideae it has not been found in the tribes Podalyrieae and Sophoreae. At least one species from each of the other tribes produces canavanine. In three genera, some species produce canavanine while others do not.These data are presumed to be of taxonomic significance and have been interpreted as support for chromosomal information indicating that the tribes Mimosoideae and Caesalpinioideae diverged relatively early from the "stem" line which is now represented by the Papilionoideae.
L-Canavanine, the principal nonprotein amino acid of certain leguminous plants, is a potent L-arginine antimetabolite. This natural product has demonstrative antineoplastic activity against a number of human cancers. Recent studies with MIAPaCa-2 and CFPAC have established canavanine’s potential anticancer activity against these human pancreatic adenocarcinomas. Canavanine has promise as a lead compound in the development of a chemotherapeutic agent for the treatment of human pancreatic carcinoma, but it has not been adequately investigated. Greater study of canavanine and its derivatives is needed to fully realize the experimental and therapeutic value of this naturally-occurring non-protein amino acid, and to obtain a chemotherapeutic agent of clinical value in treating human carcinomas.
Caution must be taken in the prevelant use of the pentacyanoammonioferrate reagent for the detection of L-canavanine in biological materias. This reagent reacts with L-histidine at neutral pH to form a pentacyanoammonioferate-histidine complex that is mistaken readily for its canavanine-containing counterpart.
research Hedysarum mackenziei Richardson (wild sweet pea, bear root) is widely regarded as toxic and warnings about confusing it with its edible cousin Hedysarum alpinum Richardson (Eskimo potato) abound. To find the chemical basis for this claim, we performed an exhaustive comparison of the secondary chemistry between the two plants as well as a search for nitrogen containing metabolites (alkaloids) in both species. No chemical basis for toxicity could be found. These results were consistent with a subsequent cytotoxic assay performed on an extract of H. mackenziei. Finally, a critical examination of the literature could find no credible evidence that H. mackenziei is toxic in spite of these widespread rumors.
Many of the 200 or so non-protein amino acids synthesized by higher plants are related structurally to the constituents of common proteins. L-Canavanine, the guanidinooxy structural analogue of L-arginine, is representative of this group. It has provided valuable insight into the biological effects and the mode of action of non-protein amino acids which acts as analogues of the protein amino acids. The arginyl-tRNA synthetases of numerous canavanine-free species charge canavanine, and canavanine is subsequently incorporated into the nascent polypeptide chain. Production of canavanine-containing proteins ultimately can disrupt critical reactions of RNA and DNA metabolism as well as protein synthesis. Canavanine also affects regulatory and catalytic reactions of arginine metabolism, arginine uptake, formation of structural components, and other cellular precesses. In these ways, canavanine alters essential biochemical reactions and becomes a potent antimetabolite of arginine in a wide spectrum of species. These deleterious properties of canavanine render it a highly toxic secondary plant constituent that probably functions as an allelochemic agent that deters the feeding activity of phytophagous insects and other herbivores.
The toxicity of L-canavanine was investigated because of its demonstrated potential as an antitumor drug. This natural product was only slightly toxic to Sprague-Dawley rats following a single sc injection: the LD50 was 5.9 +/- 1 8 g/kg in adult rats and 5.0 +/- 1.0 g/kg in 10-day-old rats. Following a single dose of 2.0 g/kg, the systemic clearance value for canavanine in adult rats was 0.114 liter/hr, the volume of distribution at steady state was 0.154 liter, and the half-life was 1.56 hr. Forty-eight percent of the dose was excreted unaltered in the urine following an iv injection, and 16% of a sc dose was recovered in the urine. Bioavailability of a 2.0 g/kg sc dose was 72%. Single oral doses of canavanine were less toxic to adult rats than sc injections. Bioavailability of a 2.0 g/kg po dose was 43%, and only 1% of the administered canavanine was recovered in the urine. Twenty-one percent of the administered canavanine remained in the gastrointestinal tract 24 hr after an oral dose. Less than 1% of a 2.0 g/kg dose of L-[guanidinooxy-14C]canavanine was incorporated into the proteins of adult and neonatal rats 4 or 24 hr following administration. Repeated sc administration of canavanine resulted in more severe toxicity. Weight loss and alopecia were observed in rats given daily sc canavanine injections for 7 days. Food intake was decreased by 80% in adult rats subjected to this dosing regimen, but returned to normal after canavanine injections were terminated. Histological studies of tissues from adult rats treated with 3.0 g/kg canavanine daily for 6 days revealed pancreatic acinar cell atrophy and fibrosis. Serum amylase and lipase levels were elevated following one sc injection of 2.0 g/kg canavanine; after three daily injections both serum enzymes were depleted. Elevations in serum glucose and urea nitrogen, and depletion of cholesterol, were observed. The most significant changes were severe attenuations of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity.
It would seem prudent for physicians caring for patients with SLE to include questions concerning the ingestion of alfalfa in their medical-history repertoire and to caution their patients against ingesting alfalfa until its role in the induction of reactivation of SLE in human beings has been clarified.
Hematologic and serologic abnormalities similar to those observed in human systemic lupus erythematosus (SLE) developed in cynomolgus macaques fed alfalfa sprouts. L-Canavanine sulfate, a constituent of alfalfa sprouts, was incorporated into the diet and reactivated the syndrome in monkeys in which an SLE-like syndrome had previously been induced by the ingestion of alfalfa seeds or sprouts.
The polyisoprenylated benzophenones, chamones I and II, were isolated from the trunk latex of Clusia grandiflora (Clusiaceae) growing in southeastern Venezuela. A third benzophenone, nemorosone II, was isolated from the pollinator reward resin of the female flowers of the same plant. Chamone I and nemorosone II are structurally similar, differing only in the degree of prenylation. Bioassays of chamone I and nemorosone II using the honeybee pathogens, Paenibacillus larvae and Paenibacillus alvei, demonstrate that both have potent antibacterial activity, and that their structural differences affect both their bactericidal efficacies and their aqueous mobilities.
l-Canavanine, l-2-amino-4-(guanidinooxy)butyric acid, is a potentially toxic nonprotein amino acid of certain leguminous plants. Many species are prolific canavanine producers; they divert enormous nitrogen resource to the storage of this single natural product. Canavanine, a highly effective protective allelochemical, provides a formidable chemical barrier to predation and disease.
The accumulated experimental evidence leaves little doubt that the key element in the ability of canavanine to function as an effective protective allelochemical is its subtle structural mimicry of arginine which makes it an effective substrate for amino acid activation and aminoacylation, and its marked diminution in basicity relative to arginine which mediates the production of structural aberrant, dysfunctional canavanyl proteins.
The biological burdens of canavanyl protein formation by canavanine-treated Manduca sexta larvae were carried throughout their remaining life cycle. Protein-based sequestration of canavanine prevented turnover and clearance of the free amino acid, and undoubtedly contributed significantly to the antimetabolic character of this protective allelochemical.
Dencichine (beta-N-oxalyl-L-alpha,beta-diaminopropionic acid) is a haemostatic agent present in important Chinese medicinal herbs such as Panax notoginseng, as well as other Panax species. It is also a reported neurotoxic agent found in Lathyrus sativus (grass pea seed). A selective analytical method incorporating hydrophilic interaction chromatography with positive electrospray ionization tandem mass spectrometry (HILIC/ESI-MS/MS), for the analysis of dencichine in Panax plant species, was developed. Using multiple reaction monitoring (MRM) mode, underivatized dencichine, a small and highly polar compound, was selectively detected and quantified. The contents of dencichine in raw and steamed Panax notoginseng roots, 11 pairs of raw and steamed P. notoginseng herbal products, Panax ginseng roots, and Panax quinquefolium roots, were analyzed and compared. Optimal sensitivity of 0.3 ppm (detection limit) and 1.5 ppm (quantification limit) was achieved. The method was rapid (< or =5 min), with the HILIC peak eluting at about 1 min. Steamed P. notoginseng samples were found to contain less dencichine than the corresponding raw samples, and there were also differences among the three Panax species; raw P. ginseng and P. quinquefolium contained less dencichine than the raw P. notoginseng species. This rapid and specific method may be applied to the quantification of dencichine in complex medicinal plants and their products.
Association of SLE and alfalfa was first reported in a volunteer who developed lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia study. This was corroborated with studies in monkeys fed with alfalfa sprout that developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine homologue L-canavanine, present in alfalfa, was suspected as a cause. L-canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during protein synthesis. Aberrant canavanyl proteins have disrupted structure and functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few cases remains controversial. Epidemiological studies on the relationship between alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L-canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were negative. L-canavanine incorporation may be more efficient in the presence of inflammation or other conditions that can cause arginine deficiency. The L-canavanine induced apoptotic cells can be phagocytosed and a source of autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are ubiquitinated and processed via proteasome. Incorporation of L-canavanine into proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L-canavanine-induced lupus will be an interesting model of autoimmunity induced by the modification of self-proteins at the translational level.
Wildflowers Along the Alaska Highway. Anchorage, AK: Alaskakrafts
- V E Pratt
Pratt VE. Wildflowers Along the Alaska Highway. Anchorage, AK: Alaskakrafts; 1991.
How Chris McCandless died
- J Krakauer
Krakauer J. How Chris McCandless died. 2013. Available
at: http://www.newyorker.com/online/blogs/books/2013/09/
how-chris-mccandless-died.html. Accessed May 7, 2014.
The Merck Index. Whitehouse Station, NJ: Merck
- O ' Neil
O'Neil MJ, ed. The Merck Index. Whitehouse Station, NJ:
Merck; 2006.
- J Alcocer-Varela
- D Alarcon-Segovia
- Reply
Alcocer-Varela J, Alarcon-Segovia D. Reply. Arthritis
Rheum. 1985;28:1200.
The silent fire: ODAP and the death of Chris McCandless
- R Hamilton
Hamilton R. The silent fire: ODAP and the death of Chris
McCandless. 2012. Available at: http://www.christo
phermccandless.info/Ronald-Hamilton/ronald-hamilton-in
tothewild1.html. Accessed May 7, 2014.
Tanaina Plantlore: Dena'ina K'et'una. Fairbanks, AK: Alaska Native Language Center
- P R Kari
Kari PR. Tanaina Plantlore: Dena'ina K'et'una. Fairbanks, AK: Alaska Native Language Center; 1991.
Wildflowers Along the Alaska Highway.
- Pratt V.E.
Tanaina Plantlore: Dena’ina K’et’una.
- Kari P.R.