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1.
Masahiro Ohsugi Yasuko Inoue Keiko Takami Mayumi Namikawa 《Bioscience, biotechnology, and biochemistry》2013,77(8):1879-1880
The biological effects of raw winged bean seeds were investigated with feeding experiments on rats, and the effects of lectin (phytohemagglutinin) present in the seeds are discussed. Administration of a 30% raw winged bean diet caused strong growth depression in young rats, and led to death within 10 ~ 20 days, inducing severe damage to the small intestine of the rats. Significant morphological changes of the intestinal mucosa were observed with a microscopic investigation. As the lethal effect was eliminated by autoclaving but not removed with supplementation of 0.5% l-methionine to the raw winged bean diet, the lectin was assumed to be closely related to the deleterious effects of raw winged bean. In vitro and in vivo digestion tests of the lectin revealed that the winged bean lectin had resistance to peptic, pancreatic and membrane digestions. The hemagglutinating activity was also detected in the intestinal mucosa and faeces from rats ingesting the raw winged bean or its purified lectin. The binding action of lection to mucosal epitheliums of the gastrointestinal tract is suggested to be the initial step of the deleterious effects induced by the winged bean lectin. 相似文献
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Yoshihara Teruhiko Ichihara Akitami Sakamura Sadao 《Bioscience, biotechnology, and biochemistry》2013,77(11):1822-1824
The synthesis of dimethyl esters of dl-O,O′-dimethylfukiic acid (11) and dl-O,O′-dimethylepifukiic acid (12) are described. 相似文献
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One of the radical species produced by the reaction of dehydro-l-ascorbic acid with an α-amino acid gave a very characteristic hyperfine structure in its electron spin resonance spectrum. The same spectrum was also obtained when l-scorbamic acid was oxidized with some oxidants, indicating the formation of the radical via the oxidation of l-scorbamic acid. From the results of deuterium exchange experiments, simulation spectra and the reduction of 2,2′-nitrilodi-2(2′)-deoxy-l-ascorbic acid monoammonium salt, the radical was concluded to be monodehydro-2,2′-iminodi-2(2′)-deoxy-l-ascorbic acid. Possible formation mechanism of the radical was also discussed. 相似文献
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Summary The inhibition of D-Amino Acid Oxidase by -Keto Acid, product of the reaction with D-Amino Acid is described for the first time. Inhibition of the enzyme by -Keto--Methiolbutyric Acid (4-methylthio-2-oxobutanoic acid), product of the reaction with D-Methionine, was studied. From the results obtained it is deduced that inhibition is competitive with the substrate, the value of the inhibition constant being 1.85 10–3 M. 相似文献
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Inactivation of the lys7 Gene, Encoding Saccharopine Reductase in Penicillium chrysogenum, Leads to Accumulation of the Secondary Metabolite Precursors Piperideine-6-Carboxylic Acid and Pipecolic Acid from α-Aminoadipic Acid 下载免费PDF全文
Leopoldo Naranjo Eva Martín de Valmaseda Javier Casqueiro Ricardo V. Ullán Mónica Lamas-Maceiras Oscar Ba?uelos Juan F. Martín 《Applied microbiology》2004,70(2):1031-1039
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Michael A. Collins Nuzhath Tajuddin Kwan-Hoon Moon Hee-Yong Kim Kimberly Nixon Edward J. Neafsey 《Molecular neurobiology》2014,50(1):239-245
Chronic alcohol (ethanol) abuse causes neuroinflammation and brain damage that can give rise to alcoholic dementia. Insightfully, Dr. Albert Sun was an early proponent of oxidative stress as a key factor in alcoholism-related brain deterioration. In fact, oxidative stress has proven to be critical to the hippocampal and temporal cortical neurodamage resulting from repetitive “binge” alcohol exposure in adult rat models. Although the underlying mechanisms are uncertain, our immunoelectrophoretic and related assays in binge alcohol experiments in vivo (adult male rats) and in vitro (rat organotypic hippocampal-entorhinal cortical slice cultures) have implicated phospholipase A2 (PLA2)-activated neuroinflammatory pathways, release of pro-oxidative arachidonic acid (20:4 ω6), and elevated oxidative stress adducts (i.e., 4-hydroxynonenal-protein adducts). Also, significantly increased by the binge alcohol treatments was aquaporin-4 (AQP4), a water channel enriched in astrocytes that, when augmented, may trigger brain (esp. cellular) edema and neuroinflammation; of relevance, glial swelling is known to provoke increased PLA2 activities or levels. Concomitant with PLA2 activation, the results have further implicated binge alcohol-elevated poly (ADP-ribose) polymerase-1 (PARP-1), an oxidative stress-responsive DNA repair enzyme linked to parthanatos, a necrotic-like neuronal death process. Importantly, supplementation of the brain slice cultures with docosahexaenoic acid (22:6 ω3) exerted potent suppression of the induced changes in PLA2 isoforms, AQP4, PARP-1 and oxidative stress footprints, and prevention of the binge alcohol neurotoxicity, by as yet unknown mechanisms. These neuroinflammatory findings from our binge alcohol studies and supportive rat binge studies in the literature are reviewed. 相似文献
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α-Aminoisobutyric acid is the only tertiary amino acid which is reported to occur in the proteins. Nevertheless, this amino acid has not been yet isolated from the proteins. Recently we succeeded in isolating this amino acid as white prismy crystalline substance from both acid and pepsin hydrolysate of horse hind leg muscle proteins, and this crystal was identified to be α-amino-isobutyric acid by elementary analysis, properties of this derivates, etc. 相似文献
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Volker Rudolph Francisco J. Schopfer Nicholas K. H. Khoo Tanja K. Rudolph Marsha P. Cole Steven R. Woodcock Gustavo Bonacci Alison L. Groeger Franca Golin-Bisello Chen-Shan Chen Paul R. S. Baker Bruce A. Freeman 《The Journal of biological chemistry》2009,284(3):1461-1473
Nitrated derivatives of fatty acids (NO2-FA) are pluripotent
cell-signaling mediators that display anti-inflammatory properties. Current
understanding of NO2-FA signal transduction lacks insight into how
or if NO2-FA are modified or metabolized upon formation or
administration in vivo. Here the disposition and metabolism of
nitro-9-cis-octadecenoic (18:1-NO2) acid was investigated
in plasma and liver after intravenous injection in mice. High performance
liquid chromatography-tandem mass spectrometry analysis showed that no
18:1-NO2 or metabolites were detected under basal conditions,
whereas administered 18:1-NO2 is rapidly adducted to plasma
thiol-containing proteins and glutathione. NO2-FA are also
metabolized via β-oxidation, with high performance liquid
chromatography-tandem mass spectrometry analysis of liver lipid extracts of
treated mice revealing nitro-7-cis-hexadecenoic acid,
nitro-5-cis-tetradecenoic acid, and nitro-3-cis-dodecenoic
acid and corresponding coenzyme A derivatives of 18:1-NO2 as
metabolites. Additionally, a significant proportion of 18:1-NO2 and
its metabolites are converted to nitroalkane derivatives by saturation of the
double bond, and to a lesser extent are desaturated to diene derivatives.
There was no evidence of the formation of nitrohydroxyl or conjugated ketone
derivatives in organs of interest, metabolites expected upon
18:1-NO2 hydration or nitric oxide (•NO) release. Plasma
samples from treated mice had significant extents of protein-adducted
18:1-NO2 detected by exchange to added β-mercaptoethanol.
This, coupled with the observation of 18:1-NO2 release from
glutathione-18:1-NO2 adducts, supports that reversible and
exchangeable NO2-FA-thiol adducts occur under biological
conditions. After administration of [3H]18:1-NO2, 64% of
net radiolabel was recovered 90 min later in plasma (0.2%), liver (18%),
kidney (2%), adipose tissue (2%), muscle (31%), urine (6%), and other tissue
compartments, and may include metabolites not yet identified. In aggregate,
these findings show that electrophilic FA nitroalkene derivatives (a)
acquire an extended half-life by undergoing reversible and exchangeable
electrophilic reactions with nucleophilic targets and (b) are
metabolized predominantly via saturation of the double bond and
β-oxidation reactions that terminate at the site of acyl-chain
nitration.The reaction of unsaturated fatty acids with nitric oxide (•NO)- and
nitrite species,
including nitrogen dioxide (•NO2), peroxynitrite
(ONOO–), and nitrous acid (HNO2), yields a complex
array of oxidized and nitrated products
(1–4).
The mechanisms of biological fatty acid nitration, the structural isomer
distribution of nitrated fatty acids
(NO2-FAs)2
and the signaling actions of specific NO2-FA regioisomers remain
incompletely characterized. Current data reveal that, during fatty acid
oxidation and nitration, vinyl nitro regioisomers represent a component of
these products that display distinctive chemical reactivities and
receptor-dependent signaling actions. Here, we investigate the metabolic fate
of the nitroalkene derivative of oleic acid
(1,
2).Unsaturated fatty acid nitration was first described in model studies of
air-pollutant-induced lipid oxidation where lipids were exposed to high
concentrations of •NO2
(5,
6). More recently nitrated
unsaturated fatty acids have been reported as products of acidic reactions of
, radical chain termination
reactions induced by •NO
(7–10),
and the oxidation of to
•NO2 by the leukocyte-derived enzyme myeloperoxidase
(1). Various mechanisms can
mediate the formation of nitroalkene derivatives of unsaturated fatty acids
(11), including homolytic
attack of •NO2
(12), reaction of
•NO2 with a pre-existing fatty acid carbon-centered radical
(2,
13), and the protonation of
nitrite under acidic conditions
(pH 5.5 and lower) to yield an array of HNO2-derived nitrating
species (3,
14). The conditions promoting
fatty acid nitration by •NO and
species (low
oxygen tension, radical formation, and low pH) are not expected to be broadly
distributed systemically (e.g. in plasma or extracellular fluids).
Rather, nitration reactions will preferably occur during inflammatory or
metabolic stress in microenvironments such as the intermembrane space of
mitochondria, the low pH environment of the digestive tract, and activated
macrophage and neutrophil-rich compartments. Moreover, the acidic,
replete and low O2
tension conditions that promote nitration reactions are characteristic of
inflammatory loci. Although multiple reactions leading to accelerated
formation of nitrating species occur at specific anatomic sites, plasma levels
of nitrated fatty acids are expected to be low due to events described
herein.Robust electrophilic reactivity and avid nuclear lipid receptor ligand
activity have conferred to the class of fatty acid nitroalkene derivatives
potent anti-inflammatory properties that occur predominantly via
non-cGMP-dependent mechanisms. Nitro derivatives of oleic and linoleic acid
inhibit leukocyte and platelet activation
(15), vascular smooth muscle
proliferation (16),
lipopolysaccharide-stimulated macrophage cytokine secretion
(17), activate peroxisome
proliferator-activated receptor-γ
(1,
18), and induce endothelial
heme oxygenase 1 expression
(19). NO2-FA also
potently modulate nuclear factor-erythroid 2-related factor 2/Kelch-like
ECH-associating protein 1 (Nrf2/Keap1)
(16,
17) and nuclear factor
κB (NFκB)-regulated inflammatory signaling
(17). Previous observations of
the •NO-mediated, cGMP-dependent vessel relaxation induced by
NO2-FA were made under serum- and lipid-free conditions. More
recently, it has been appreciated that micellar and membrane stabilization of
NO2-FA prevents Nef-like aqueous decay reactions and consequent
•NO release, supporting that the predominant signaling actions mediated
by NO2-FA are •NO and cGMP-independent
(20,
21).Current data indicate that electrophilic adduction of biological targets
primarily accounts for NO2-FA signal transduction. The high
electronegativity of NO2 substituents, when bound to an alkenyl
carbon of fatty acids, confers an electrophilic nature to the adjacent
β-carbon and enables Michael addition reaction with nucleophiles such as
protein His and Cys residues. This process, termed nitroalkylation
(22), results in the
clinically detectable and reversible adduction of the nucleophilic thiol of
glutathione (GSH) and both cysteine and histidine residues of
glyceraldehyde-3-phosphate dehydrogenase
(23). Furthermore, inhibition
of NFκB signaling occurs via nitroalkylation of p65 subunit thiols
(17), and recent findings
reveal that NO2-FA activation of peroxisome proliferator-activated
receptor-γ is uniquely induced by covalent nitroalkylation of the ligand
binding domain
Cys-285.3Multiple reports support the endogenous generation and presence of nitrated
fatty acids (1,
24), first observed in bovine
papillary muscles as a vicinal nitrohydroxyeicosatetraenoic acid
(25). Nitrolinoleate has been
detected in human blood plasma and cholesteryl nitrolinoleate in human plasma
and lipoproteins (4,
26), with hyperlipidemic and
post-prandial conditions elevating plasma levels of NO2-FA. Further
support for the inflammatory generation of NO2-FA comes from
lipopolysaccharide and interferon-γ-activated murine J774.1 macrophages,
where increased nitration of the acyl chain of cholesteryl linoleate was
paralleled by increased macrophage expression and activity of nitric-oxide
synthase 2 (27).To date, insight into the mechanisms of nitroalkene signaling actions
overshadows knowledge of the generation, trafficking, and metabolism of
nitroalkenes in vivo. Appreciating that NO2-FA derivatives
are detectable clinically, and that their levels increase following
•NO-dependent oxidative reactions
(4,
28), challenges still exist in
their routine detection. Because the in vivo administration of
NO2-FA may exert anti-inflammatory benefit, the disposition and
metabolite profiles of these species in vivo is of relevance. Here we
report that only 2.4% of nitrooctadecenoic acid (18:1-NO2) is
immediately detectable in the vascular compartment as native
18:1-NO2 upon intravenous injection in mice, with the remaining
pool of 18:1-NO2 (a) reversibly bound to plasma and tissue
thiols via Michael addition; (b) metabolized to nitro-octadecanoic
acid (18:0-NO2) and nitro-octadecadienoic acid
(18:2-NO2); and (c) catabolized by hepatic
β-oxidation following thioester formation with coenzyme A. 相似文献
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4-Aminotetrolic Acid : New Conformational-restricted Analogue of γ-Aminobutyric Acid 总被引:2,自引:0,他引:2
RECENT studies strongly support a role for γ-aminobutyric acid (GABA) as an inhibitory transmitter at certain synapses in the mammalian central nervous system. Structure activity correlations of many GABA analogues implicate both the intramolecular distance between the zwitterionic centres and the rotational freedom of the molecule as important factors governing the synaptic activity of these substances1. The following observations provide pertinent information about the active conformation(s) of GABA recognized by the receptor. (1) Muscimol, an isoxazole isolated from Amanita muscaria, seems to function as a GABA analogue as its inhibitory action on central neurones is comparable with that of GABA both in potency2 and with respect to antagonism by bicuculline3. Molecular orbital calculations suggest that GABA and muscimol can assume similar conformations as zwitterions with the charged centres (N+ and 0?) at least 5 and, more likely, 6 Å apart4. (2) The selective GABA antagonist bicuculline exhibits some degree of structural similarity with particular conformations of GABA and muscimol3. (3) X-ray crystallography indicates that GABA exists in a partially folded conformation in the solid state5,6. (4) A model of the GABA receptor proposes that GABA adopts a folded conformation with a distance of less than 4.4 Å between the charged centres7. Observations (1) and (2) suggest extended conformations for GABA, while (3) and (4) suggest folded conformations. 相似文献
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Mudcharee Julotok Atul K. Singh Craig Gatto Brian J. Wilkinson 《Applied and environmental microbiology》2010,76(5):1423-1432
Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C15:0 fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37°C and 10°C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C4, C5, and C6 branched-chain carboxylic acid, and C3 and C4 straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein.Listeriosis is a severe and life-threatening human infection encompassing meningoencephalitis, meningitis, focal infections in the immunocompromised, and stillbirths and neonatal sepsis due to infection of pregnant women (2). The disease is caused by the Gram-positive food-borne pathogen Listeria monocytogenes, which is responsible for common-source and sporadic disease involving a variety of different foods (27). Listeriosis has a high fatality rate (24). The U.S. Department of Agriculture has a zero tolerance policy for L. monocytogenes in ready-to-eat products, and high costs are associated with product recalls.L. monocytogenes has a remarkably low minimum growth temperature, e.g., −0.1°C (34), and thus the organism can multiply to dangerous levels when food is kept at refrigeration temperatures. We are interested in the molecular mechanisms of L. monocytogenes psychrotolerance, with a view to applying this knowledge to improve the control of the growth of the organism. Although the adaptations involved in low-temperature tolerance are global in scope, we have focused on changes in fatty acid composition that result in homeoviscous adjustments of membrane fluidity (31, 36). L. monocytogenes has a fatty acid composition that is dominated to an unusual extent (90% or more) by branched-chain fatty acids (BCFAs); the major fatty acids are anteiso-C15:0, anteiso-C17:0, and iso-C15:0. Numerous studies have shown that the major change in fatty acid composition when L. monocytogenes is grown at low temperatures is an increase in the content of anteiso-C15:0 fatty acid to 65% or more of the total (1, 12, 23, 25, 26, 28). Two cold-sensitive mutants with Tn917 insertions in the branched-chain α-keto acid dehydrogenase gene complex (bkd) were deficient in BCFAs, grew poorly at low temperatures, and had decreased membrane fluidity; all of these defects could be restored by growth in the presence of 2-methylbutyrate (2-MB), a precursor of odd-numbered anteiso fatty acids, including anteiso-C15:0 fatty acid (1, 7, 13, 37). We believe that anteiso-C15:0 fatty acid imparts fluidity to the cytoplasmic membrane, as revealed by its low phase transition temperature in model phospholipids (18) and disruption of the close packing of fatty acyl chains (21, 35).The amino acids isoleucine, leucine, and valine are the starting points for the biosynthesis of odd-numbered anteiso, odd-numbered iso, and even-numbered iso fatty acids, respectively (18, 37). The amino acids are converted to their corresponding α-keto acid derivatives through the activity of branched-chain amino acid transaminase. Branched-chain α-keto acid dehydrogenase (Bkd) then converts these α-keto compounds to branched-chain acyl coenzyme A (acyl-CoA) primers of fatty acid biosynthesis (18). These primers are then used to initiate fatty acid biosynthesis through the activity of β-ketoacyl-acyl carrier protein synthase III (FabH), which prefers branched-chain acyl-CoAs to acetyl-CoA as substrates (4, 22, 32). β-Keto-acyl carrier protein synthase II (FabF) is responsible for subsequent rounds of elongation until the acyl chain reaches 14 to 17 carbon atoms (36).We wished to ascertain whether we could manipulate the fatty acid composition of L. monocytogenes by feeding precursors that favored the production of fatty acids other than anteiso-C15:0 and thereby inhibit the growth of the organism, especially at low temperatures. Kaneda (15, 16) has grouped Bacillus subtilis fatty acids into four pairs based on the precursors from which they are generated, i.e., anteiso-C15:0 and C17:0 from isoleucine, iso-C15:0 and C17:0 from leucine, iso-C14:0 and C16:0 from valine, and n-C14:0 and n-C16:0 from acetate or butyrate. The proportions of the fatty acids could be modulated by precursor feeding. We have studied the effects of feeding the potential fatty acid precursors branched-chain amino acids, branched-chain α-keto acids, short branched-chain carboxylic acids, short straight-chain carboxylic acids, medium-length straight-chain carboxylic acids, branched-chain C6 carboxylic acids, and sodium diacetate (Fig. (Fig.1)1) on the growth and fatty acid composition of L. monocytogenes. Various short-chain carboxylic acids are used as food preservatives (5, 8, 29), and it was of interest to see whether any of them had an effect on the fatty acid composition of L. monocytogenes. Precursors giving rise to C5 and C6 branched-chain acyl-CoA derivatives, propionate, and butyrate had significant impacts on growth and fatty acid composition. Acetate and precursors that were metabolized to acetyl-CoA had minor effects on fatty acid composition, indicating that their preservative action is not due to effects on fatty acid composition.Open in a separate windowFIG. 1.Structures of potential fatty acid precursors. 相似文献
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