Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “METHIONINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2002

D-Methionine and cisplatin ototoxicity in the guinea pig: D-methionine influences cisplatin pharmacokinetics.

D-Methionine has recently been advocated as a protectant against cisplatin toxicity. The use of systemic D-methionine as a protector was studied in 58 guinea pigs. Kinetics and distribution of [11CH(3)]D-methionine was analysed by positron emission tomography. Cisplatin and the monohydrated complex of cisplatin was quantified in blood ultrafiltrate using reversed-phase liquid chromatography with post-column derivatisation. Administration of 300 mg/kg of D-methionine caused a 30% decrease in the area under the concentration-time curve (AUC) of cisplatin. The toxic effect of cisplatin was studied after dose adjustment of cisplatin, i.e. with similar cisplatin AUC in the group receiving D-methionine and the saline control group. A significant ototoxic effect, measured as difference in pre- and 96 h post-treatment electrophysiological hearing threshold (auditory brainstem response), was observed at stimulus frequencies of 30 and 20 kHz. There was no difference between the groups in the extent of threshold shift. Quantitative outer hair cell counts showed a similar loss of cells in the two groups. All animals had a significant increase in plasma-creatinine but there was no difference between the groups. The results indicate that protection from cisplatin ototoxicity by systemic D-methionine can be explained by a lowered systemic exposure to the drug.

Animals↗
PubMed1993

[Methodical studies of metabolism oriented methionine requirement determination in broiler chicks. 2. Effect of feeding frequency on methionine utilization].

The effect of feeding frequency (daily 2 times feeding for 1 hour or 6 times feeding for 30 minutes) and a different methionine content of the diet on weight gain, N-balance and metabolic 35S-methionine degradation was investigated in broiler chickens. Weight gain and N-balance were not improved by increased feeding frequency. At the high feeding frequency, weight gain and N-balance were even depressed when diets with methionine deficiency (without methionine supplementation) were fed. No effects of feeding frequency and the amount of DL-methionine supplementation on the level of excreted 35S after i.v. injection of 35S-methionine were observed.

Animal Feed↗
PubMed1991

Methionine kinetics and balance at the 1985 FAO/WHO/UNU intake requirement in adult men studied with L-[2H3-methyl-1-13C]methionine as a tracer.

The upper range of the requirement for methionine plus cystine in healthy adults was proposed in 1985 by FAO/WHO/UNU to be 13 mg.kg body wt-1.d-1. To explore the validity of this estimate, five healthy, young adult men were given for 7 d a diet based on an L-amino acid mixture supplying 13 mg methionine.kg-1.d-1 (87 mumol.kg-1.d-1) without cystine. Constant intravenous infusions of L-[2H3-methyl-1-13C]methionine were given on days 5 and 7 while subjects were in the fed and postabsorptive states, respectively. Estimates were made of methionine oxidation, and daily methionine balance was derived from the intake-oxidation data. For the five subjects, methionine balances were -0.9, +0.7, +3.5, -3.1, and -3.8 mg kg-1.d-1, or -6, +5, +23, -21, and -26 mumol.kg-1.d-1. These findings lead to the conclusion that the upper range of the requirement for methionine plus cystine probably exceeds 13 mg.kg-1.d-1 in healthy young adults. The implications of this conclusion for establishing an appropriate amount of sulfur amino acids in an amino acid requirement pattern for adults is discussed.

Adult↗
PubMed1995

Tracer kinetic studies on a methionine-supplemented soy-based infant formula using 1-13C- and 15N-methionine as tracers.

A tracer-kinetic study using 1-13C- and 15N-labeled L-methionine was conducted in order to measure the retention rate of free methionine added to commercially-produced soy-based infant formulas. Twelve male infants, fed on a soy formula, received a single-pulse labeling by oral administration of L-1-13C-methionine (5 mg/kg) and L-15N-methionine (10 mg/kg). The abundance of expired 13C-labeled CO2 was measured up to 7 h after administration at 15-, 30-, and 60-min intervals. Additionally, enrichment of total 15N and 15N in urinary ammonia were determined up to 48 h after administration. Retention rates of the labeled carboxyl group amounted to an average of 91.2% (SD 4.1) of the intake. A similar retention rate was measured for the 15N-label of methionine (90.0%, SD 4.3). The data point at the efficacy of methionine supplementation of soy-based infant formulas.

Ammonia↗
PubMed1987

Processing of the initiation methionine from proteins: properties of the Escherichia coli methionine aminopeptidase and its gene structure.

Methionine aminopeptidase (MAP) catalyzes the removal of amino-terminal methionine from proteins. The Escherichia coli map gene encoding this enzyme was cloned; it consists of 264 codons and encodes a monomeric enzyme of 29,333 daltons. In vitro analyses with purified enzyme indicated that MAP is a metallo-oligopeptidase with absolute specificity for the amino-terminal methionine. The methionine residues from the amino-terminal end of the recombinant proteins interleukin-2 (Met-Ala-Pro-IL-2) and ricin A (Met-Ile-Phe-ricin A) could be removed either in vitro with purified MAP enzyme or in vivo in MAP-hyperproducing strains of E. coli. In vitro analyses of the substrate preference of the E. coli MAP indicated that the residues adjacent to the initiation methionine could significantly influence the methionine cleavage process. This conclusion is consistent, in general, with the deduced specificity of the enzyme based on the analysis of known amino-terminal sequences of intracellular proteins (S. Tsunasawa, J. W. Stewart, and F. Sherman, J. Biol. Chem. 260:5382-5391, 1985).

Amino Acid Sequence↗
PubMed1995

Design of an antifungal methionine inhibitor not antagonized by methionine.

Only a few biosynthetic pathways in fungal cells have been used as antifungal targets. Therefore, the number of antifungals has been limited, and a cross-drug resistance among them has emerged in the therapy of mycoses. Under such circumstances, the identification of an antifungal with a new mode of action is highly desirable. By infecting mice with a mutant of C. albicans deficient in the sulfate assimilation pathway, we have discovered a new target for the discovery of antifungal agents. We have proven that azoxybacilin inhibits the sulfate assimilation pathway by showing its inhibitory activity for [35S]SO4 incorporation into proteins. We have also demonstrated that azoxybacilin was taken up into fungal cells via an active transport system specific for methionine. This sharing of the uptake system with methionine may explain the mechanism by which the antifungal activity of azoxybacilin is antagonized by methionine, and led us to design azoxybacilin derivatives that lack the structural feature of amino acids and, at the same time, have increased hydrophobicity to give higher non-specific permeability through the cell membrane. As a result, we have found that ester derivatives of azoxybacilin were not antagonized by methionine in their uptake, and that they showed antifungal activity independent of methionine. The benzyl ester of azoxybacilin was the same as azoxybacilin in its mode of action, but was not markedly antagonized by methionine at concentrations up to 1 mg/ml. These results suggest that azoxybacilin may not merely interfere with the sulfate assimilation pathway.

Aminobutyrates↗
PubMed1985

Influence of methionine hydroxy analog and DL-methionine on rumen protozoa and volatile fatty acids.

Three lactating Holstein cows with rumen cannulae were used in a 3 X 3 Latin square arrangement of treatments to study effects of methionine source on ciliated protozoa numbers and volatile fatty acid concentrations in the rumen. Cows were fed total mixed diets twice daily of 60% grain mix, 21% corn silage, and 19% alfalfa hay (dry basis). Methionine hydroxy analog, DL-methione, and sodium sulfate were added on an equal sulfur basis. Experimental periods were 14 d with four rumen samples taken daily on d 13 and 14. Total ciliated protozoa were higher when cows were fed DL-methionine than when fed methionine hydroxy analog or sodium sulfate. Ruminal concentrations of butyric acid and isobutyric acid were higher for the DL-methionine treatment than for analog or sodium sulfate treatments. Isovaleric acid concentrations were also higher in fluid from cows fed methionine compared with cows fed the analog.

Animals↗
PubMed1985

Influence of three concentrations of DL-methionine or methionine hydroxy analog on milk yield and milk composition.

Sixty-eight Holstein cows were fed diets consisting of 60% concentrate and 40% forage, dry basis. Diets were supplemented with DL-methionine or methionine hydroxy analog at either 0, .1, .2, or .3% of the concentrate. Dietary protein averaged 14% of total dry matter on all diets except for a positive control diet, which was 19% crude protein. Data were collected beginning 4 d postpartum and continued through 116 d postpartum. Milk yield was not influenced by either DL-methionine or methionine hydroxy analog. Supplementation with DL-methionine resulted in a quadratic response in milk fat percentage (3.34, 3.58, 3.72, 3.42) at 0, .1, .2, and .3% of the concentrate, respectively. Milk fat percentage increased linearly (3.34, 3.64, 3.60, 3.73) with supplementation of methionine hydroxy analog at 0, .1, .2, and .3%, respectively.

Animal Feed↗
PubMed1997

Response of lactating cows to methionine or methionine plus lysine added to high protein diets based on alfalfa and heated soybeans.

Lactation diets based on wilted alfalfa silage and heated whole soybeans are common in the midwestern US. We examined the milk production response of multiparous Holstein cows to the addition of ruminally protected methionine at two percentages to a basal total mixed ration. An additional total mixed ration included both methionine and lysine supplementation. Sixteen Holstein cows in early lactation were used in a replicated 4 x 4 Latin square design with 21-d periods. Milk production, milk composition, and dry matter intake were determined for the last 5 d of each period. Milk production (41.5 kg/d), dry matter intake (25.9 kg/d), and milk fat concentration (3.26%) were unaffected by the supplementation of amino acids. The addition of methionine increased milk protein concentration and yield linearly. Each gram of methionine increased milk protein yield by 4 g, and milk protein concentration increased from 2.89 to 2.99% with the addition of 10.5 g/d of methionine. The proportion of casein N in total milk N was unaffected by treatment. The addition of lysine did not elicit a response. Total mixed rations based on alfalfa haylage, heated soybeans, and animal proteins were clearly limited by their methionine content but were adequate in their lysine content.

Ammonia↗
PubMed1980

Methionine-cystine interrelationships in chicks and rats fed diets containing suboptimal levels of methionine.

Studies were continued with both chicks and rats on the previously reported (featherston and Rogler, 1978) growth depression observed when a crystalline amino acid diet adequate in all nonsulfur-containing amino acids and containing .2% DL-methionine and .2% L-cystine was supplemented with an additional .2% L-cystine. In the present investigation, an average growth depression of 37% was observed in chicks fed a diet containing .4% L-cystine and .2% DL-methionine as compared with chicks fed a diet containing .2% L-cystine and the same level of methionine. A comparable depression was noted when cystine was replaced by L-cysteine. In contrast, an additional .2% of another amino acid (L-tryptophan) did not depress growth. When the high and low cystine diets were meal-fed, results obtained were similar to those observed with ad libitum feeding, but the magnitude of the difference was reduced. Foot-pad lesions, similar to those described in turkey poults fed methionine-deficient diets, were observed in two experiments. Factorial analysis of plasma amino acids indicated that the total of all amino acids analyzed was significantly (P < .05) higher in chicks fed the lower cystine or cysteine diets. Plasma methionine was slightly lower (P < .10) but plasma cystine was significantly (P < .05) higher in chicks fed the cystine or cysteine supplemented diets. A study with .2 and .4% L-cystine and 200, 600, and 2000 mg/kg of choline (factorial design) demonstrated a significant (P < .05) depression in weight gain due to the added L-cystine, no significant (P < .05) differences due to choline, and the absence of a cystine-choline interaction. No detrimental effects were observed when weanling rats were fed a crystalline amino acid diet containing .1% DL-methionine and .2% L-cystine supplemented with additional L-cystine.

Animal Nutritional Physiological Phenomena↗
PubMed1983

A comparison of DL-methionine and Liquimeth as a source of supplemental methionine for the turkey poult.

Two experiments were conducted to determine the efficacy of DL-methionine and DL-methionine-Na (Liquimeth) as a source of methionine for the turkey poult. A corn-soybean meal diet containing sulfate-free trace minerals and no supplemental choline was used. In two experiments the poults were fed the experimental diets from 1 to 21 days of age. The experimental diets and deionized water were offered ad libitum. A linear increase in growth was obtained by adding increments of either DL-methionine or Liquimeth. There were no significant differences in body weight of poults receiving equivalent amounts of methionine from the two sources. Feed efficiency was also equal for each level of supplemental methionine from the two sources.

Animals↗
PubMed1984

Biological efficacy of liquid methionine and methionine hydroxy analogue-free acid in chicks.

An experiment was conducted to determine biological efficacies of DL-methionine-Na (Liquimeth) and DL-methionine hydroxy analogue (MHA)-free acid (Alimet) relative to DL-methionine in Single Comb White Leghorn male chicks. A crystalline amino acid mixture devoid of sulfur-containing amino acids was used for the basal diet, and the test substances were added at .1, .2, and .3% levels, equivalent to DL-methionine on a molar basis, in place of cornstarch. By a slope ratio assay using chick growth as a criterion, the relative biological efficacies of DL-MHA-free acid and DL-methionine-Na to DL-methionine were found to be 70 and 113%, respectively, on a molar basis.

Animal Feed↗
PubMed1993

Liquid methionine hydroxy analog (free acid) and DL-methionine attenuate calcium-induced kidney damage in domestic fowl.

To evaluate the possibility that kidney damage may be induced by the commercial practice of feeding high-Ca (HCa) prelayer rations, and to evaluate the protective efficacy of supplementing HCa diets with liquid methionine hydroxy analog free acid or DL-methionine, 12-wk-old female Single Comb White Leghorn pullets were fed one of the following corn-soybean meal-based diets until they reached 22 wk of age: normal-Ca (NC, 1% Ca); HCa (HC, 3.5% Ca); HCa supplemented with .34 or .68% liquid methionine hydroxy analog free acid (HC3A or HC6A); or HCa supplemented with .3 or .6% DL-methionine (HC3DL or HC6DL). The unsupplemented HC diet caused a significant reduction in kidney mass and a significant increase in the incidence of gross kidney damage and urolithiasis in pullets necropsied at 22 wk of age. Calcium-induced kidney damage was attenuated in a dose-response fashion by supplementing the HC diet with liquid methionine hydroxy analog and DL-methionine. None of the diets caused a significant metabolic acidosis. Plasma uric acid concentrations were not predictive of the extent of Ca-induced kidney damage. Analyses of glomerular size distributions indicated that subclinical or "hidden" kidney damage may not progressively develop into urolithiasis as hens mature. When compared with hens reared on the NC diet, rearing hens on the HC, HC3A, HC3DL, HC6A, or HC6DL diets did not consistently affect hen-day egg production, egg mass, eggshell mass, percentage eggshell, or bone mineralization.

Animals↗
PubMed2006

[Effect of feeding pre-L-methionine on high-cell-density fermentation for S-adenosyl-L-methionine production].

The yield of S-adenosyl-L-methionine (SAM) by saccharomyces cerevisiae fermentation was affected by the strategy of feeding L-methionine. The effects that feeding strategies and the amount of precursor L-methionine had on the production of SAM by saccharomyces cerevisiae G14 were investigated. The results showed that feeding L-methionine could obviously improve the accumulation of SAM, and both the biomass and SAM yield relied heavily on different feeding strategies. In our work, it was found that total amount of L-methionine added should be no less than 0.7g per 10 grams of dry cell weight. Five different feeding strategies had been investigated in our experiment, and such comparison indicated that favorable results could be achieved as the biomass reached the status of high cell density (120g/L). If 9 grams of the precursor L-methionine was introduced once and for all, the accumulation of SAM reached maximum of 4.31g/L at the 18th hour after addition; if the precursor amino acid was fed at a rate of 2g/h in 5 h, maximum yield of 4.98g/L was achieved at the 28th hour after feeding. Thus high cell density fermentation can be successfully applied to SAM production by Saccharomyces cerevisiae with the consequence of over 130g/L of biomass gained using the above two strategies.

Bioreactors↗
PubMed1971

Studies on acute methionine toxicity. I. Nucleolar disaggregation in guinea pig hepatic cells with methionine or ethionine and its reversal with adenine.

The effects of methionine and ethionine on the fine structure of hepatic cell nucleoli of guinea pigs and rats were investigated. A single intraperitoneal injection of methionine into guinea pigs results in the disruption of nucleolonema as early as 2 hours after the injection. By 4 hours, nucleoli show complete fragmentation consisting of many small fragments and small remnants of nucleoli. Large aggregates of interchromatinic granules and condensation of chromatin appear in the nucleoplasm. These changes are remarkably similar to the lesions induced by ethionine in the liver of the rat or the guinea pig. The methionine-induced nuclear and nucleolar lesions persist up to 10 hours after the injection. The administration of adenine 4 hours after the methionine injection reverses the nucleolar lesions by 8 hours. The appearance of incompletely reconstructed nucleoli with twisted ropelike structures suggests a pattern of recovery very similar to the adenine-induced nucleolar reformation in ethionine-treated rats. Injecting methionine into rats induced no nucleolar abnormalities. It is suggested that the mechanism of nucleolar fragmentation induced by methionine or ethionine is related to the accumulation of S-adenosyl compounds with concomitant ATP deficiency in the liver.

Adenine↗
PubMedDate not supplied

Effect of combination therapy with a methionine-mitomycin C conjugate and a methionine-deficient diet on tumor growth.

BACKGROUND: We investigated effects of a combination therapy of a methionine-mitomycin C conjugate (M-M conj) and methionine-free nutrition both in vitro and in vivo, compared to mitomycin C (MMC) administration alone. MATERIALS AND METHODS: The human esophageal cancer cell line, KE-3, incubated in either standard or methionine-free media, was treated with phosphate buffered saline (PBS), M-M conj in PBS, or MMC in PBS. The rate of cell survival was determined. The tumor bearing mice were maintained on either a standard or methionine-free diet (MFD) and treated with PBS, MMC, or M-M conj. RESULTS: The lowest tumor cell survival rate was found with the M-M conj plus methionine-free media at every dose tested (p < 0.05). Tumor weight was significantly lower with the M-M conj plus MFD than in any other group (p < 0.003). CONCLUSION: Methionine targets MMC to tumor during administration of MFD.

Animals↗
PubMed1983

Chemotherapeutic potential of methionine analogue inhibitors of tumor-derived methionine adenosyltransferases.

Two isozymes of ATP:L-methionine S-adenosyltransferase (MAT) were fractionated from rat Novikoff solid hepatoma. Their Km values for L-methionine and/or their inhibition constants for various L-methionine analogues were significantly different from the kinetic constants obtained for three isozymes fractionated from normal rat liver. Ki values for cycloleucine and (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, presented for each tumor and liver isozyme, indicate that (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid was the more potent inhibitor. Dixon plots were also used to test a series of amino acid analogues [cycloleucine, 1-aminocyclobutanecarboxylic acid, 1-aminocyclohexanecarboxylic acid, (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, L-2-amino-4-hexynoic acid, (Z)-L-2-amino-5-chloro-trans-4-hexenoic acid, L-ethionine, S-n-propyl-DL-homocysteine, S-n-butyl-DL-homocysteine, and seleno-DL-ethionine] of methionine for inhibitory potency. Fixed L-methionine concentrations were used to determine the concentration of inhibitor necessary to inhibit the MAT reaction by 50%. Differential inhibitory activities of the amino acid analogues were noted between the tumor and rat liver isozymes thus supporting the suggestion that tumor-derived MAT isozymes may provide an exploitable target for cancer chemotherapy.

Animals↗
PubMed2004

Essential role of methionine residues in calmodulin binding to Bordetella pertussis adenylate cyclase, as probed by selective oxidation and repair by the peptide methionine sulfoxide reductases.

Bordetella pertussis, the causative agent of whooping cough, secretes among other virulence factors an adenylate cyclase (AC) toxin that is able to enter into eukaryotic cells where it is activated upon binding to endogenous calmodulin (CaM) and synthesizes supraphysiological cAMP levels. In vivo, the AC toxin, through its specific interaction with the CD11b/CD18 integrin, primarily targets phagocytic cells such as neutrophils and macrophages. Because neutrophil priming and activation result in the production of reactive oxygen species that may cause intracellular oxidation, we have examined the biological consequences of the oxidation of CaM methionines upon its interaction with AC. We show here that the interaction of CaM with AC is dependent on the reduced state of methionines, because oxidation of all methionine residues of CaM dramatically decreases its affinity for AC. Peptide methionine sulfoxide reductases A (MsrA) and B (MsrB) were able to partially reduce the oxidized CaM, and these partially "repaired" forms could interact with AC nearly as efficiently as the native protein. We further showed that the CaM.AC complex is resistant to oxidation with tert-butylhydroperoxide, and we identified methionine residues 109, 124, and 145 as critical for binding to AC. The resistance of the AC.CaM complex to oxidation and the ability of AC to be efficiently activated by partially oxidized CaM molecules should allow the toxin to exert its cytotoxic effects on activated neutrophils and contribute to the host colonization.

Adenylyl Cyclases↗