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# The isolation of a toxic substance from Agenized wheat flour

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... More than 60 years ago it was observed that domestic animals developed seizures after being fed bleached (agenized) flour [95]. The bleaching process oxidized methionine in the flour to MSO [96], and later investigations demonstrated that systemic administration of MSO to rats and mice inhibits GS and results in severe convulsive seizures [97][98][99][100]. Moreover, chronic infusion of MSO locally into the hippocampus of rats results in inhibition of GS, and subsequent recurrent seizures [17,80]. ...
Article
Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer's disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.
... MSO has been described as the chemical responsible for seizures induced in various animals after consumption of agenized flour, during the mid-1950s [157][158][159]; and it was therefore used to induce seizures in different animals, essentially rats and mice with characterized EEG alterations before and during seizures [124,154,160,161]. Moreover, some plants of the Cnestis genus, from Madagascar and Asia, were used to kill running dogs by causing severe convulsions. ...
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Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.
Article
Those nonprotein amino acids found in food and fodder plants and known to be toxic to man and domestic animals are described. These include toxins from many legume genera including Lathyrus, from other higher plant families, from seaweeds, and from fungi. Some inhibit protein synthesis, while others are incorporated into proteins with toxic effects. Basic processes such as urea synthesis and neurotransmission may be disrupted. The probable roles of nonprotein amino acids in protecting plants against predators, pathogens, and competing plant species are considered. The need to learn more of the nutritive value of nontoxic nonprotein amino acids and to explore the potential of others either as drugs or as leads to drugs in human and veterinary medicine is emphasized.
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1.1. The sulfur of methionine sulfone intraperitoneally injected into rats is rapidly excreted.2.2. Most of the sulfur is excreted in the urine; only a small part of this has been oxidized to sulfate.3.3. Methionine sulfone sulfur occurs in the urine in at least three forms. Some free methionine sulfone is excreted; a major fraction is a conjugate of methionine sulfone with glutamic acid.4.4. The significance of these findings is discussed.
Article
Sulfoximines have been largely disregarded in medicinal chemistry for a long time. However, recently, they have risen to the apparent level of stardom on the drug discovery scene. Considering the outstanding properties of sulfoximines, this versatile functional group has advanced to implementation in several drug discovery programs. Currently, this fashionable functional group can be found in various hit-to-lead and lead optimization studies in early stages and in several compounds currently in clinical trials. Herein, we review recent developments to demonstrate the scope and limitations of this interesting and versatile functional group in medicinal chemistry and drug discovery.
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Non-protein amino acids are common in plants and are present in widely consumed animal feeds and human foods such as alfalfa (Medicago sativa), which contains canavanine, and lentil (Lens culinaris), which contains homoarginine. Some occur in wild species that are inadvertently harvested with crop species. Some non-protein amino acids and metabolites can be toxic to humans, e.g. Lathyrus species contain a neurotoxic oxalyl-amino acid. Some potential toxins may be passed along a food chain via animal intermediates. The increased interest in herbal medicines in the Western countries will increase exposure to such compounds.
The biochemistry of an uncomplicated deficiency of copper is studied. A moderate to advanced depletion of copper does not affect the activity or level of the following: liver-slice respiration, tricarboxylic acid cycle, fatty-acid oxidation, amino-acid oxidation, oxidative phosphorylation, anaerobic glycolysis, catalase, DPN-cytochrome c reductase, transmethylase, choline oxidase, isocitric dehydrogenase, succinic dehydrogenase, malic dehydrogenase, glutamic dehydrogenase, oxidation of glucose and pyruvate by brain mitochondria, urinary amino-acids, plasma protein, magnesium, calcium, sodium, potassium, or inorganic phosphate. Activities of cytochrome oxidase and succinoxidase are reduced at this stage of deficiency. The loss of succinoxidase activity is due to the depletion of cytochrome oxidase which is severe and progressive from a very early stage of deficiency. Haem $\alpha$ is almost completely absent from copper-deficient tissues, and it is suggested that this is the limiting component of the cytochrome oxidase system. Mitochondria from deficient rats are very susceptible to 'ageing'. The 'ageing' effect is shown to be due to loss of and reversed by addition of the pyridine nucleotides, glutathione and manganese. The susceptibility to 'ageing' is thought to be secondary to an impaired synthesis of phospholipid. Extreme copper deficiency leads to a grave loss of the capacity of mitochondria to oxidize any substrate; this is almost certainly due both to the negligible activity of cytochrome oxidase and an acceleration of the effect of 'ageing'. Isocitric dehydrogenase activity is increased and DPN-cytochrome c reductase decreased at this stage; the reasons are discussed.
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Preliminary experiments on the effect of methionine sulphoximine on the developing chick and on transplantable tumours - Volume 10 Issue 3 - Edward Mellanby
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Sir Edward MelIanby had accepted a cordial invitation from the Editorial Committee of the Annual Review of Biochemistry to contribute this Prefatory Chapter. Unhappily, before he had completed his seventy-first year, he died suddenly on Sunday, January 30, 1955, about mid-day, after he had spent the morning at his research. His draft of the introduction to his contribution to this volume is printed below in the section“ to British Biochemistry.” For nearly six years after retiring from the post of Secretary of the Medical Research Council, he continued to engage in research work and in many scientific affairs. He was, for example, active in the Royal Society, of which he had been a Fellow for 30 years, and he was one of its Vice-Presidents. Sir Henry Dale has recently completed an Obituary Notice of Mellanby for the Royal Society (1955); this tribute is of such grandeur as perhaps only a man of Sir Henry's eminence could contribute, and I shall quote from this to give the weight of wisdom, experience, and knowledge to this chapter.
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Extracts of the polyphenolic fractions of the water-soluble metabolites (that is, the complex mixtures of plant phenols extracted by ethyl acetate) were prepared from apple and pear varieties characterized by different degrees of resistance to the scab pathogens. Qualitative differences were chiefly interspecific and extracts of resistant varieties did not contain major components lacking in those of less-resistant varieties of the same species. Cultural reactions of distinct clones of each pathogen to the extracts, in the presence of various basal media, were observed. Growth and sporulation were inhibited independently by extracts of less-resistant as well as resistant host varieties. The clones were not equally susceptible, those of Venturia inaequalis showing relationships between inhibition of sporulation by host polyphenols and their varietal host ranges. Fluctuations in pathogenicity of a clone of V. pirina during storage in culture with periodic re-isolation from Williams pear were reflected in its reactions to the extracts. Both pathogens were capable of decomposing the polyphenols. The results suggested that qualitative and quantitative variations in the polyphenolic host metabolites, including differences in their relative proportions, in relation to nitrogenous and other nutritional factors, are of potential significance in the determination of pathogenicity and varietal resistance.
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material. The studywas initiated partlyinordertoinvestigate thenature oftheprotein-carbohydrate linkage, butthisgoal couldnot be achievedby themethodsthen available. Someprogress hasbeenmade inthis problemby more recentstudies and Johansen, Marshall & Neuberger (1960) havegiventhemost probable values forthemannose,glucosamine and acetyl contents ofthewholeprotein andofaglycopeptide isolated fromit.Theprobability thatthese aretheonlysugarspresentwasindicated. Itis thepurposeofthispapertodescribe thepreparationand some oftheproperties ofthisglycopeptide, andtoconsider thenatureofthechemical bondlinking thecarbohydrate to theprotein. A briefdescription ofthisworkwas reported earlier (Johansen, Marshall & Neuberger, 1958). Cunningham, Nuenke& Nuenke (1957)and Jevons(1958) havealsogivenshortaccountsof their findings onthesamesubject.
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The free amino acid composition of the 75% ethanol extracts of a strain of Sarcina lutea varied considerably depending on the composition of the growth medium. Differences in hydroxyproline content were particularly significant. The amino acid composition of the ethanol-extracted cell residues remained constant.
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Methionine sulfoximine, the toxic principle of the agenized protein diet, produces in the cat a complex syndrome characterized by behavioral and convulsive changes. In a series of 50 cats, the following features were most consistently observed:1Sniffing movements, involving the upper lip, nose and lower eyelid, and accompanied by profuse salivation and impairment of consciousness.2Episodic behavioral changes consisting of head-turning, sniffing, and crouching movements strongly suggesting apprehension, orientation and fear.3Running fits at the onset of which the animal may appear fearful or hysterical.4Generalized tonic-clonic convulsions.A detailed description of the syndrome is given and the influence of external stimuli and such factors as dosage of toxic agent, age, nutritional status of experimental animal, upon the character, frequency, rapidity of onset, and duration of the various behavioral and convulsive phenomena are discussed.The significance of the sulfoximine syndrome, as regards its biochemical and behavioral similarities to certain types of human epilepsy and its value as an experimental tool i n the investigation of the patho-physiology of seizures are discussed.RÉUMÉLa méthionine sulfoximine, principe toxique du régime de protéine agénisée, produit chez le chat un syndfrome complexe charactérisé par des changements du comportement et des convulsions. Les caractéristiques suivants ont été constamment observées sur une série de 50 chats:1Mouvements de reniflument comprenant la lèvre supérieure, le nez et la paupière inférieure, accompagnés de salivation profuse et d'abaissement de la conscience.2Des changements épisodiques du comportement consistant en tournement de la těte, reniflement et mouvements de rampement donnant fortement l'impression de crainte, d'orientation et d'appréhension.3Accès de course folle au début desquels l'animal peut sembler très craintif ou hystérique.4Convulsions toniques-cloniques généralisées.L'auteur donne une description détaillée du syndrome et décrit l'influence de stimuli externes et celle de facteurs tels que le dosage d'un agent toxique, de l'ǎge et de l'état de nutrition de l'animal d'expérience, sur le caractère, la fréquence et la rapidité du début de la crise, la durée du changement du comportment et des phénomènes convgulsifs.La significatin du syndrome de la sulfoximine fait l'objet d'une discussion en ce qui concerne les similitudes biochimiques et celles du comportement à l'endroit de certains types d'épilepsie humaine ainsi que sa valeur en tant qu'instrument d'expérience dans des recherches sur la pathophysiologie des crises.
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Elevated blood ammonia (hyperammonemia) is believed to be a major contributor to the neurological sequelae following severe liver disease. Ammonia is cleared via two main mechanisms, the urea cycle pathway and the glutamine synthetase reaction. Recent studies of genetically modified animals confirm the importance of the urea cycle, but also suggest that the glutamine synthetase reaction is more important than previously recognized. While the liver clears about two-thirds of the body’s ammonia via the combined action of the urea cycle and glutamine synthetase, extrahepatic tissues do not express all the components required for performing a complete urea cycle and therefore depend on the glutamine synthetase reaction for ammonia clearance. The brain is particularly vulnerable to the effects of hyperammonemia, which include impaired extracellular potassium buffering and brain edema. Moreover, the glutamine synthetase reaction is intimately linked to the metabolism of the excitatory and inhibitory neurotransmitters glutamate and gamma aminobutyric acid (GABA), implicating a key role for this enzyme in neurotransmission. This review discusses the emerging roles of glutamine synthetase in brain pathophysiology, particularly aspects related to ammonia homeostasis and hepatic encephalopathy.
Article
Innovation has frequently been described as the key to drug discovery. However, in the daily routine, medicinal chemists often tend to stick to the functional groups and structural elements they know and love. Blockbuster cancer drug Velcade (bortezomib), for example, was rejected by more than 50 companies, supposedly because of its unusual boronic acid function (as often repeated: "only a moron would put boron in a drug!"). Similarly, in the discovery process of the pan-CDK inhibitor BAY 1000394, the unconventional proposal to introduce a sulfoximine group into the lead series also led to sneers and raised eyebrows, since sulfoximines have seldom been used in medicinal chemistry. However, it was the introduction of the sulfoximine group that finally allowed the fundamental issues of the project to be overcome, culminating in the identification of the clinical sulfoximine pan-CDK inhibitor BAY 1000394. This Minireview provides an overview of a widely neglected opportunity in medicinal chemistry-the sulfoximine group.
Article
Oxidation is one of the deterioration reactions of proteins in food, whose importance does not lag behind that of others such as Maillard, lipation or protein‐polyphenol reactions. While research on protein oxidation has led to an accurate perception on the processes and consequences in physiological systems, knowledge on specific implications of protein oxidation in food or the role of “oxidized” dietary protein for the human body is comparatively scarce. Food protein oxidation can occur during the whole processing axis, from primary production to intestinal digestion. The present review wants to summarize the current knowledge and mechanisms of food protein oxidation from a chemical, technological and nutritional‐physiological viewpoint and give a comprehensive classification of the individual reactions. Different analytical approaches will be compared, and the relationship between oxidation of food proteins and oxidative stress in vivo will be critically evaluated.
Article
Oxidation is one of the deterioration reactions of proteins in food, whose importance does not lag behind that of others such as Maillard, lipation or protein‐polyphenol reactions. While research on protein oxidation has led to an accurate perception on the processes and consequences in physiological systems, knowledge on specific implications of protein oxidation in food or the role of “oxidized” dietary protein for the human body is comparatively scarce. Food protein oxidation can occur during the whole processing axis, from primary production to intestinal digestion. The present review wants to summarize the current knowledge and mechanisms of food protein oxidation from a chemical, technological and nutritional‐physiological viewpoint and give a comprehensive classification of the individual reactions. Different analytical approaches will be compared, and the relationship between oxidation of food proteins and oxidative stress in vivo will be critically evaluated.
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In regard to epileptic seizures, a common terminology for ictal semiotics and classification is the end goal. Progress made in either the understanding of the underlying pathophysiology or treatment of epileptic seizure disorders, whether in veterinary medicine or human medicine, is easier to identify and apply comparatively. To aid in the clinical discussion of epileptic seizures, the entire process of a seizure has been defined to occur in different elements or phases. This chapter addresses three general classification paradigms. The first is the phenomenological classification of seizures. The second would be the etiological classification of seizures. Finally and most importantly would be the epileptic syndrome the seizure type and etiology fall under.
Article
Epilepsy is a common and devastating neurological disorder characterized by recurrent and unprovoked spontaneous seizures. One leading hypothesis for the development and progression of epilepsy is that large-scale changes in gene transcription and protein expression contribute to aberrant network restructuring and hyperexcitability, resulting in the genesis of repeated seizures. Current research shows that epigenetic mechanisms, including posttranslational alterations to the proteins around which DNA is coiled, chemical modifications to DNA, and the activity of various noncoding RNA molecules exert important influences on these gene networks in experimental epilepsy. Key findings from animal models have been replicated in humans using brain tissue obtained from living patients at the time of neurosurgical resection for pharmacoresistant epilepsy. These findings have spurred efforts to target epigenetic processes to disrupt or modify epilepsy in experimental models with varying degrees of success. In this review, we will (1) summarize the epigenetic mechanisms implicated in epileptogenesis and epilepsy, (2) explore the influence of metabolic factors on epigenetic mechanisms, and (3) assess the potential of using epigenetic markers to support diagnosis and prognosis. Translation of these findings may guide the development of molecular biomarkers and novel therapeutics for prevention or modification of epileptic disorders.
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Einführung und Überblick. Chromatographie ist — nach Gerhard Hesses Metapher1 — ein Verfahren zur Trennung eines Stoffgemisches in seine Komponenten nach dem Prinzip des Wettrennens der Molekeln über eine Hindernisstrecke. Am schnellsten ans Ziel kommen diejenigen Molekeln, die mit den Hindernissen am besten fertig werden, die anderen folgen in der Reihenfolge, wie sie die Hindernisse „nehmen“ können.
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This chapter discusses the preparation and properties of “active formaldehyde” and “active formate.” “Active formaldehyde,” an adduct between formaldehyde and tetrahydrofolic acid, has been identified as N5,N10-methylenetetra-hydrofolic acid (I). The compound is synthesized most easily by allowing tetrahydrofolic acid to interact with an excess of formaldehyde at a slightly acidic pH and purifying the product by column chromatography. There are three known forms of “active formate”—namely, N5-formyl-tetrahydrofolic acid (folinic acid), N10-formyltetrahydrofolic acid, and N5,N10-methenyltetrahydrofolic acid, which are encountered in enzymatic systems. Folinic acid is commercially available. N5,N10-Methenyltetrahydrofolic acid (II) is readily prepared as a stable, crystalline material by the procedure discussed in the chapter, and N10-formyltetrahydrofolate can be generated in situ by adjusting solutions of the methenyl derivative to pH 7 or higher. When the prepared “active formate” product is examined by descending paper chromatography on Whatman No. 1 paper with 1.0 M formic acid–0.01 M mercaptoethanol as the solvent system, a single white fluorescent spot is observed under ultraviolet light. The failure of this spot to respond to the spray reagent, which reductively cleaves many folic acid compounds at the C9–N10 linkage, is referable to the stabilizing effect of the methenyl bridge between the N5- and N10-positions.
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In a review on terminal amino acids in peptides and proteins published in 1944 Fox (132) was able to give the position of only one amino acid, phenylalanine, in one protein, insulin, with some degree of certainty [Jensen and Evans (185)]. In the intervening period great advances in our knowledge of amino acid sequences in peptides and proteins have been made. It is now possible to write the complete structural formula for insulin and for many naturally occurring, short-chain polypeptides, two of which, oxytocin and vasopressin, have been synthesised. Much progress has also been made in elucidating the structure of proteins larger than insulin.
Article
Innovation ist häufig als der Schlüssel zur Wirkstoff‐Findung beschrieben worden. Doch in der täglichen Routine neigen Medizinalchemiker dazu, nur das Instrumentarium der funktionellen Gruppen und Strukturelemente zu verwenden, das sie bereits kennen und lieben. Das Blockbuster‐Krebsmedikament Velcade (Bortezomib) wurde beispielsweise von mehr als 50 Unternehmen abgelehnt, vermutlich wegen seiner ungewöhnlichen Boronsäuregruppe (“Only a moron would put boron in a drug!”). Auch im Entwicklungsprozess des pan‐CDK‐Inhibitors BAY 1000394 sorgte der unkonventionelle Vorschlag, eine Sulfoximingruppe in die Leitstruktur einzuführen, zunächst für Spott und Stirnrunzeln, da Sulfoximine selten in der medizinischen Chemie verwendet worden sind. Jedoch war es gerade die Sulfoximingruppe, die es schließlich ermöglichte, die fundamentalen Probleme des Projekts zu überwinden, und so zur Identifizierung des klinischen pan‐CDK‐Inhibitors BAY 1000394 führte. Der vorliegende Kurzaufsatz gibt einen Überblick über eine weithin vernachlässigte Chance in der medizinischen Chemie – die Sulfoximingruppe.
Article
Paper chromatograms of hydrolysates of 118 micro-organisms were examined in a study of the distribution of α, e-diaminopimelic acid and other amino-acids. A method for the identification of α, e-diaminopimelic acid is described. Diaminopimelic acid was found in nearly all the bacteria examined, except for the Gram-positive cocci, Streptomyces spp., and Actinomyces spp. It was also found in blue-green algae but in no other algae, nor in fungi, yeasts, plant viruses, or protozoa. Each species examined showed a different amino acid composition. β-Alanine and α- and γ-aminobutyric acids were sometimes found, often in several species of the same genus. Seven unidentified ninhydrin-reacting spots were recorded; none of them had the wide distribution of diaminopimelic acid.
Article
The nutritive function of proteins for monogastric animals may be simply to supply the body with amino acids. However, the complexities of digestion, absorption and metabolism imply that amino acid composition, determined chemically after hydrolysis, can only be a very rough guide (usually setting upper limits) to the nutritional value of proteins. Chemical reactions which may affect nutritional values of proteins are discussed at length. Chemical tests, for determining the extent to which these reactions have occurred, are increasing, both in number and usefulness. However, to derive practical benefits from chemical tests, frequent parallel nutritional assessments must be conducted using animals.
Article
Death came suddenly, and without recognized warning, to Sir Edward Mellanby on 30 January 1955, before he had completed his 71st year. Nearly six years earlier he had retired, on reaching the official age-limit, from the Secretaryship of the Medical Research Council, which he had held for 16 years. During this period the range and the influence of the Council’s activities for the promotion and support of medical research had undergone a most notable expansion, primarily in the United Kingdom, but widely beyond it also in the British Commonwealth; and Mellanby’s enlightened and resourceful enterprise in proposal and planning, and his vigorous drive in administrative action, had undoubtedly been dominant factors in this remarkable development. Like his only predecessor in the appointment, the late Walter Morley Fletcher, Mellanby had been the Council’s chief executive officer in much more than a merely official sense. Yet, during all the years in which he had carried that heavy load of official responsibility, he had succeeded in maintaining a direct and personal activity in the researches which had so long provided for him, and also for his devoted wife and scientific partner, the central aim and interest of their joint working lives.
Glucose is the main fuel for cell life, and supports a number of different processes in providing cells with energy. Excess glucose is polymerized into glycogen, which is an energy-glucose store. Alterations in glycogen content and/or synthesis have been reported in human neuropathologies, such as Alzheimer's disease, epilepsies and cancer. Epileptic foci are hypometabolic during the interictal period, and probably hypermetabolic during crisis. Animal models of epilepsies are used for studying the reasons why neurons suddenly and temporally synchronize their activity. One model associates seizures of the “grand mal” type with cortical glycogen accumulation: induction of epileptiform crisis by methionine sulfoximine (MSO). The glycogen accumulation, observed in astrocytes only, occurs as soon as the preconvulsive period. High glycogen has also been demonstrated in primary cultures of astrocytes. Abnormal glycogen content has been characterized in various types of cancers, including gliomas. High invasion properties, spontaneous resistance to chemotherapeutic drugs, and a mean prognosis of 12 months characterize glioblastomas, the highest grade of gliomas that inevitably leads to death. The various therapeutic means, including surgery, chemicaland radio-therapies, and gene therapy have thus far been inefficient in significantly improving patient survival. Glycogen synthesis was targeted in cell lines from murine and human glioblastomas by an antisense glycogen synthase cDNA strategy; and the inhibition of glycogen synthesis in these cell lines decreases both in vitro and in vivo invasiveness. Glycogen can therefore be considered as putatively involved in at least two different pathologies of the brain, such as epilepsies and cancer. This abnormal glycogen content and synthesis can be proposed as putative diagnostic and therapeutic targets in brain pathologies.
Article
Glabrin, the toxic principle of Cnestis glabra isolated from root bark, was identified as S-(3-amino-3-carboxypropyl)-S-methyl sulphoximine (methionine sulphoximine) by spectroscopic and chemical means. The natural occurrence of this toxic methionine derivative is reported for the first time.
Article
Es wird ein neues kristallisiertes Nebenalkaloid aus Salamandra maculosa, das Cycloneosamandion, beschrieben, das erst aus stark alkalischer Lösung ausgeäthert werden kann. Es ist ein Isomeres des Samandarons und des Samandions der Summenformel C19H29NO2. Ein Sauerstoffatom liegt wie im Samandaron als Carbonylgruppe in einem 5-Ring vor, eine zweite Carbonylgruppe bildet mit einem sekundären Stickstoff eine sehr stabile Ketonammoniak-Gruppierung. Die Base kann daher tautomer als tertiäres Amin mit der Gruppierung und als sekundäres Amin mit den Gruppen reagieren. Sie enthält 3 carbocyclische Ringe. — Zahlreiche Umsetzungen der neuen Base, die auch in den sauerstofffreien Grundkörper, das Neosaman C10H33N, übergeführt werden konnte, werden beschrieben. Schließlich wird auf Grund der Annahme, daß das Cycloneosamandion konstitutionell mit den Hauptalkaloiden Samandarin und Samandaron verwandt ist, eine mögliche Konstitutions-formel vorgeschlagen.
Article
An investigation into the nature of the bleaching observed in bread after mixing part of the dough as a batter in high-speed machinery is described. The bleaching effect is attributed to the action of unsaturated-fat oxidases and in particular to that of lipoxidase. The simultaneous improvement† obtained under these conditions of mixing is found to be independent of lipoxidase action but dependent on free access of molecular oxygen to the dough. The presence of molecular oxygen is also necessary for the action of lipoxidase. Arising from this work, a process for making bread from unbleached untreated flour by mixing in an oxygen-enriched atmosphere is briefly suggested.
Article
The chemical fate of methyl bromide absorbed by wheat under the conditions of fumigation has been studied. Whole-wheat flour was exposed to 14C-labelled methyl bromide. The fat, starch, gluten, and water-soluble fractions were prepared from the exposed flour and their 14C-content assayed. The gluten or protein fraction was responsible for some 80% of the decomposition of the absorbed fumigant. By measuring the 14C of the volatile products obtained on treating the gluten with sodium hydroxide or hydriodic acid under different conditions, it was shown that the decomposition of methyl bromide in gluten was due almost entirely to methylation with the formation of 50% of N-methyl derivatives, 30% of dimethyl sulphonium derivatives, and of 20% of methoxyl and thiomethoxyl derivatives in about equal proportions. Similar results were obtained when gluten alone was exposed to the labelled fumigant. The production of free methanol in the flour by hydrolysis of the absorbed fumigant was about 10% or less. The rate of spontaneous decomposition of the dimethyl sulphonium compounds formed as a result of fumigation was estimated by using wheat which had been grown on 35S-labelled sulphate.
Article
In this first of a series of four papers, an investigation is described into the possible production of abnormal substances by the action of ten times the normal level of chlorine dioxide treatment of flour. Quantitative aspects of the amino-acid content of the flour protein after treatment have also been studied. Comparison has been made with untreated and normally treated flours and with flour treated with ten times the normal amount of nitrogen trichloride. No abnormal ninhydrin-reactive substances resulting from the treatment have been found and, of the essential amino-acids, only tryptophan has been reduced in proportion, to an extent greater than 10% after heavy treatment with nitrogen trichloride. Of the non-essential amino-acids, cystine has been reduced to about 75% by heavy treatment with chlorine dioxide or nitrogen trichloride. The remaining three papers of the series will deal with the biological aspects of the investigation.
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EstimationDistributionPurification and PropertiesSpecificityNature of the EnzymeMechanism of the ReactionReferenceDiscussion
• T H Newkirk
• M Handelman
Newkirk, T. H. & Handelman, M. (1949). Indu8tr. Engng Chem. 41, 452.
• H R Bentley
• E E Mcdermott
• J Pace
• J K Whitehead
• T Moran
Bentley, H. R., McDermott, E. E., Pace, J., Whitehead, J. K. & Moran, T. (1949a). Nature, Lond., 163, 675.
• L Reiner
• F Misani
• T W Fair
• P Weiss
• M G Cordasco
Reiner, L., Misani, F., Fair, T. W., Weiss, P. & Cordasco, M. G. (1950). J. Amer. chem. soc. 72, 2297.
• A Tiselius
• B Drake
• L Hagdahl
Tiselius, A., Drake, B. & Hagdahl, L. (1947). Experientia, 3, 21.
• J C Baker
Baker, J. C. (1921). U.S. Patent, 1,367,530.
• J R Wagner
• C A Elvehjem
Wagner, J. R. & Elvehjem, C. A. (1944). J. Nutrit. 28, 431. Biochem. 1951, 48
• G J Cox
• H King
• C P Berg
Cox, G. J., King, H. & Berg, C. P. (1929). J. biol. Chem. 81, 755.
• S Moore
• W H Stein
• T Moran
• G W Newell
• T C Erickson
• W E Gilson
• S N Gershoff
• C A Elvehjem
Moore, S. & Stein, W. H. (1949). J. biol. Chem. 178, 53. Moran, T. (1947). Lancet, 2, 289. Newell, G. W., Erickson, T. C., Gilson, W. E., Gershoff, S. N. & Elvehjem, C. A. (1947). J. Amer. med. A88. 135, 760.
• P N Campbell
• T S Work
• E Mellanby
Campbell, P. N., Work, T. S. & Mellanby, E. (1950). Nature, Lond., 165, 345.
• G S Fonken
• R Mozingo
Fonken, G. S. & Mozingo, R. (1947). J. Amer. chem. Soc. 69, 1212.
• H Svensson
Svensson, H. (1948). Advanc. prot. Chem. 4, 251.
• H R Bentley
• E E Mcdermott
• J Pace
• J K Whitehead
• T Moran
Bentley, H. R., McDermott, E. E., Pace, J., Whitehead, J. K. & Moran, T. (1950). Nature, Lond., 165, 150. Blish, M. J. (1945). Advanc. prot. Chem. 2, 337.
• D Melnick
• G R Cowgill
Melnick, D. & Cowgill, G. R. (1937). J. Nutrit. 14,401.
• S M Partridge
• R G Westall
Partridge, S. M. & Westall, R. G. (1949). Biochem. J. 44,418. Radomski, J. L., Woodard, G. & Lehman, A. J. (1948).