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Phytochemistry Reviews : Proceedings of... 2018Sequential enzymes in biosynthetic pathways are organized in metabolons. It is challenging to provide experimental evidence for the existence of metabolons as... (Review)
Review
Sequential enzymes in biosynthetic pathways are organized in metabolons. It is challenging to provide experimental evidence for the existence of metabolons as biosynthetic pathways are composed of highly dynamic protein-protein interactions. Many different methods are being applied, each with strengths and weaknesses. We will present and evaluate several techniques that have been applied in providing evidence for the orchestration of the biosynthetic pathways of cyanogenic glucosides and glucosinolates in metabolons. These evolutionarily related pathways have ER-localized cytochromes P450 that are proposed to function as anchoring site for assembly of the enzymes into metabolons. Additionally, we have included commonly used techniques, even though they have not been used (yet) on these two pathways. In the review, special attention will be given to less-exploited fluorescence-based methods such as FCS and FLIM. Ultimately, understanding the orchestration of biosynthetic pathways may contribute to successful engineering in heterologous hosts.
PubMed: 29755303
DOI: 10.1007/s11101-017-9509-1 -
The Cochrane Database of Systematic... Apr 2015Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other... (Review)
Review
BACKGROUND
Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous.
OBJECTIVES
To assess the alleged anti-cancer effect and possible adverse effects of laetrile and amygdalin.
SEARCH METHODS
We searched the following databases: CENTRAL (2014, Issue 9); MEDLINE (1951-2014); EMBASE (1980-2014); AMED; Scirus; CINAHL (all from 1982-2015); CAMbase (from 1998-2015); the MetaRegister; the National Research Register; and our own files. We examined reference lists of included studies and review articles and we contacted experts in the field for knowledge of additional studies. We did not impose any restrictions of timer or language.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs.
DATA COLLECTION AND ANALYSIS
We searched eight databases and two registers for studies testing laetrile or amygdalin for the treatment of cancer. Two review authors screened and assessed articles for inclusion criteria.
MAIN RESULTS
We located over 200 references, 63 were evaluated in the original review, 6 in the 2011 and none in this update. However, we did not identify any studies that met our inclusion criteria.
AUTHORS' CONCLUSIONS
The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk-benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative.
Topics: Amygdalin; Antineoplastic Agents, Phytogenic; Humans; Neoplasms
PubMed: 25918920
DOI: 10.1002/14651858.CD005476.pub4 -
Plant Direct Feb 2018Cyanogenic glucosides are present in many plants, including eudicots, monocots, and ferns and function as defence compounds based on their ability to release hydrogen...
Cyanogenic glucosides are present in many plants, including eudicots, monocots, and ferns and function as defence compounds based on their ability to release hydrogen cyanide. In this study, the diurnal rhythm of cyanogenic glucoside content and of transcripts and enzymes involved in their biosynthesis was monitored in cassava plants grown in a glasshouse under natural light conditions. Transcripts of 1, , / and were at minimal levels around 9 p.m., increased during the night and decreased following onset of early morning light. Transcripts of and showed more subtle variations with a maximum reached in the afternoon. Western blots showed that the protein levels of CYP71E7/11 and UGT85K4/5 decreased during the light period to a near absence around 4 p.m. and then recovered during the dark period. Transcript and protein levels of linamarase were stable throughout the 24-hr cycle. The linamarin content increased during the dark period. In the light period, spikes in the incoming solar radiation were found to result in concomitantly reduced linamarin levels. In silico studies of the promoter regions of the biosynthetic genes revealed a high frequency of light, abiotic stress, and development-related transcription factor binding motifs. The synthesis and endogenous turnover of linamarin are controlled both at the transcript and protein levels. The observed endogenous turnover of linamarin in the light period may offer a source of reduced nitrogen to balance photosynthetic carbon fixation. The rapid decrease in linamarin content following light spikes suggests an additional function of linamarin as a ROS scavenger.
PubMed: 31245705
DOI: 10.1002/pld3.38 -
Insects May 2018Chemical defences are key components in insect⁻plant interactions, as insects continuously learn to overcome plant defence systems by, e.g., detoxification, excretion... (Review)
Review
Chemical defences are key components in insect⁻plant interactions, as insects continuously learn to overcome plant defence systems by, e.g., detoxification, excretion or sequestration. Cyanogenic glucosides are natural products widespread in the plant kingdom, and also known to be present in arthropods. They are stabilised by a glucoside linkage, which is hydrolysed by the action of β-glucosidase enzymes, resulting in the release of toxic hydrogen cyanide and deterrent aldehydes or ketones. Such a binary system of components that are chemically inert when spatially separated provides an immediate defence against predators that cause tissue damage. Further roles in nitrogen metabolism and inter- and intraspecific communication has also been suggested for cyanogenic glucosides. In arthropods, cyanogenic glucosides are found in millipedes, centipedes, mites, beetles and bugs, and particularly within butterflies and moths. Cyanogenic glucosides may be even more widespread since many arthropod taxa have not yet been analysed for the presence of this class of natural products. In many instances, arthropods sequester cyanogenic glucosides or their precursors from food plants, thereby avoiding the demand for de novo biosynthesis and minimising the energy spent for defence. Nevertheless, several species of butterflies, moths and millipedes have been shown to biosynthesise cyanogenic glucosides de novo, and even more species have been hypothesised to do so. As for higher plant species, the specific steps in the pathway is catalysed by three enzymes, two cytochromes P450, a glycosyl transferase, and a general P450 oxidoreductase providing electrons to the P450s. The pathway for biosynthesis of cyanogenic glucosides in arthropods has most likely been assembled by recruitment of enzymes, which could most easily be adapted to acquire the required catalytic properties for manufacturing these compounds. The scattered phylogenetic distribution of cyanogenic glucosides in arthropods indicates that the ability to biosynthesise this class of natural products has evolved independently several times. This is corroborated by the characterised enzymes from the pathway in moths and millipedes. Since the biosynthetic pathway is hypothesised to have evolved convergently in plants as well, this would suggest that there is only one universal series of unique intermediates by which amino acids are efficiently converted into CNglcs in different Kingdoms of Life. For arthropods to handle ingestion of cyanogenic glucosides, an effective detoxification system is required. In butterflies and moths, hydrogen cyanide released from hydrolysis of cyanogenic glucosides is mainly detoxified by β-cyanoalanine synthase, while other arthropods use the enzyme rhodanese. The storage of cyanogenic glucosides and spatially separated hydrolytic enzymes (β-glucosidases and α-hydroxynitrile lyases) are important for an effective hydrogen cyanide release for defensive purposes. Accordingly, such hydrolytic enzymes are also present in many cyanogenic arthropods, and spatial separation has been shown in a few species. Although much knowledge regarding presence, biosynthesis, hydrolysis and detoxification of cyanogenic glucosides in arthropods has emerged in recent years, many exciting unanswered questions remain regarding the distribution, roles apart from defence, and convergent evolution of the metabolic pathways involved.
PubMed: 29751568
DOI: 10.3390/insects9020051 -
Heliyon Nov 2022Ferns are used as traditional and fascinating foods in many countries. They are also considered to possess important ethnomedicinal values; however, ferns are one of the... (Review)
Review
Ferns are used as traditional and fascinating foods in many countries. They are also considered to possess important ethnomedicinal values; however, ferns are one of the underutilized plant resources by both scientific and local communities. Pharmagonostical studies reveal that ferns and fern-allies possess several biological activities including antibacterial, antiviral, antifungal, antimalarial, antidiarrheal, anthelmintic, analgesic, anti-inflammatory, antidiabetic, anticancer, neuroprotective, nephroprotective, hepatoprotective, antifertility, etc. Flavonoids and terpenoids are major secondary metabolites present in ferns. Ugonins, particularly isolated from , have found diverse bioactivities. Ptaquiloside, a norsesquiterpene glucoside, found in , and , is one of the hazardous metabolites of ferns which is responsible for the toxic effect. Alkaloids are reported to be present in the ferns; however, the qualitative data are uncertain. Some fern metabolites, such as cyanogenic glycosides and terpenoids, are considered to possess defensive activity against animal attacks. Some ferns are also used for manuring as biological alternative to pesticides. Nepalese have consumed at least 33 species of ferns and fern-allies belonging to 13 families, 20 genera as cooked vegetable foods. The aim of this review is compilation of information available on their distribution, ethnomecinal values, pharmcognosy, pharmacology and phytochemistry.
PubMed: 36444246
DOI: 10.1016/j.heliyon.2022.e11687 -
Bioresource Technology Nov 2018The β-glucosidases (β-D-glucoside glucohydrolase, EC 3.2.1.21) hydrolyze glycosidic bonds of alkyl-, amino-, or aryl-β-D-glucosides, cyanogenic glucosides,... (Review)
Review
The β-glucosidases (β-D-glucoside glucohydrolase, EC 3.2.1.21) hydrolyze glycosidic bonds of alkyl-, amino-, or aryl-β-D-glucosides, cyanogenic glucosides, disaccharides and short oligosaccharides and can also catalyze the synthesis of glycosyl-bonds between different molecules via transglycosylation. Due to their ubiquitous phylogenetic distribution, substrate diversity and ability to both hydrolyze and synthesize glycosidic bonds, the catalysis and regulation of β-glucosidases have been extensively studied. Many β-glucosidases are inhibited by the reaction product glucose, and reduced catalytic activity may limit the biotechnological and industrial applications of these enzymes and this has stimulated the search for β-glucosidases that maintain their activity at high glucose concentrations. Studies of many glucose tolerant enzymes have been reported and due to the ongoing interest in these enzymes, here it has been reviewed this accumulated body of knowledge which provides valuable insights as to the kinetics, structure, regulation and evolution of glucose tolerant and glucose stimulated β-glucosidases.
Topics: Cellulases; Glucose; Glucosidases; Kinetics; Phylogeny; Substrate Specificity; beta-Glucosidase
PubMed: 30093225
DOI: 10.1016/j.biortech.2018.07.137 -
Journal of Basic and Clinical... Aug 2020Trifolium repens belongs to the family Leguminosae and has been used for therapeutic purposes as traditional medicine. The plant is widely used as fodder and leafy... (Review)
Review
Trifolium repens belongs to the family Leguminosae and has been used for therapeutic purposes as traditional medicine. The plant is widely used as fodder and leafy vegetables for human uses. However, there is a lack of a detailed review of its phytochemical profile and pharmacological properties. This review presents a comprehensive overview of the phytochemical profile and biological properties of T. repens. The plant is used as antioxidants and cholinesterase inhibitors and for anti-inflammatory, antiseptic, analgesic, antirheumatic ache, and antimicrobial purposes. This review has summarized the available updated useful information about the different bioactive compounds such as simple phenols, phenolic acids, flavones, flavonols, isoflavones, pterocarpans, cyanogenic glucosides, saponins, and condensed tannins present in T. repens. The pharmacological roles of these secondary metabolites present in T. repens have been presented. It has been revealed that T. repens contain important phytochemicals, which is the potential source of health-beneficial bioactive components for food and nutraceuticals industries.
PubMed: 32776902
DOI: 10.1515/jbcpp-2020-0015 -
The Plant Journal : For Cell and... Sep 2022Cyanogenic glucosides are important defense molecules in plants with useful biological activities in animals. Their last biosynthetic step consists of a glycosylation...
Cyanogenic glucosides are important defense molecules in plants with useful biological activities in animals. Their last biosynthetic step consists of a glycosylation reaction that confers stability and increases structural diversity and is catalyzed by the UDP-dependent glycosyltransferases (UGTs) of glycosyltransferase family 1. These versatile enzymes have large and varied substrate scopes, and the structure-function relationships controlling scope and specificity remain poorly understood. Here, we report substrate-bound crystal structures and rational engineering of substrate and stereo-specificities of UGT85B1 from Sorghum bicolor involved in biosynthesis of the cyanogenic glucoside dhurrin. Substrate specificity was shifted from the natural substrate (S)-p-hydroxymandelonitrile to (S)-mandelonitrile by combining a mutation to abolish hydrogen bonding to the p-hydroxyl group with a mutation to provide steric hindrance at the p-hydroxyl group binding site (V132A/Q225W). Further, stereo-specificity was shifted from (S) to (R) by substituting four rationally chosen residues within 6 Å of the nitrile group (M312T/A313T/H408F/G409A). These activities were compared to two other UGTs involved in the biosynthesis of aromatic cyanogenic glucosides in Prunus dulcis (almond) and Eucalyptus cladocalyx. Together, these studies enabled us to pinpoint factors that drive substrate and stereo-specificities in the cyanogenic glucoside biosynthetic UGTs. The structure-guided engineering of the functional properties of UGT85B1 enhances our understanding of the evolution of UGTs involved in the biosynthesis of cyanogenic glucosides and will enable future engineering efforts towards new biotechnological applications.
Topics: Amino Acids; Animals; Glucosides; Glycosides; Glycosyltransferases; Nitriles; Uridine Diphosphate
PubMed: 35819080
DOI: 10.1111/tpj.15904 -
International Journal of Molecular... Apr 2023Plants and phytophagous arthropods have coevolved in a long battle for survival. Plants respond to phytophagous feeders by producing a battery of antiherbivore chemical... (Review)
Review
Plants and phytophagous arthropods have coevolved in a long battle for survival. Plants respond to phytophagous feeders by producing a battery of antiherbivore chemical defences, while herbivores try to adapt to their hosts by attenuating the toxic effect of the defence compounds. Cyanogenic glucosides are a widespread group of defence chemicals that come from cyanogenic plants. Among the non-cyanogenic ones, the Brassicaceae family has evolved an alternative cyanogenic pathway to produce cyanohydrin as a way to expand defences. When a plant tissue is disrupted by an herbivore attack, cyanogenic substrates are brought into contact with degrading enzymes that cause the release of toxic hydrogen cyanide and derived carbonyl compounds. In this review, we focus our attention on the plant metabolic pathways linked to cyanogenesis to generate cyanide. It also highlights the role of cyanogenesis as a key defence mechanism of plants to fight against herbivore arthropods, and we discuss the potential of cyanogenesis-derived molecules as alternative strategies for pest control.
Topics: Animals; Herbivory; Plants; Cyanides; Glycosides; Arthropods
PubMed: 37108149
DOI: 10.3390/ijms24086982 -
Molecular Plant Jan 2018Oximes (RRC=NOH) are nitrogen-containing chemical constituents that are formed in species representing all kingdoms of life. In plants, oximes are positioned at... (Review)
Review
Oximes (RRC=NOH) are nitrogen-containing chemical constituents that are formed in species representing all kingdoms of life. In plants, oximes are positioned at important metabolic bifurcation points between general and specialized metabolism. The majority of plant oximes are amino acid-derived metabolites formed by the action of a cytochrome P450 from the CYP79 family. Auxin, cyanogenic glucosides, glucosinolates, and a number of other bioactive specialized metabolites including volatiles are produced from oximes. Oximes with the E configuration have high biological activity compared with Z-oximes. Oximes or their derivatives have been demonstrated or proposed to play roles in growth regulation, plant defense, pollinator attraction, and plant communication with the surrounding environment. In addition, oxime-derived products may serve as quenchers of reactive oxygen species and storage compounds for reduced nitrogen that may be released on demand by the activation of endogenous turnover pathways. As highly bioactive molecules, chemically synthesized oximes have found versatile uses in many sectors of society, especially in the agro- and medical sectors. This review provides an update on the structural diversity, occurrence, and biosynthesis of oximes in plants and discusses their role as key players in plant general and specialized metabolism.
Topics: Animals; Lizards; Oximes; Plants; Volatile Organic Compounds
PubMed: 29275165
DOI: 10.1016/j.molp.2017.12.014