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Environmental effects on gene expression and offspring development can be mediated by epigenetic modifications. It is well established that maternal diet influences DNA methylation patterns and phenotypes in the offspring; however, the epigenetic effects of paternal diet on developing offspring warrants further investigation. Here, we examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression. Three treatment and three control rams were bred to seven ewes, and blastocysts were flushed for RNA extraction. Semen was collected from all rams and submitted for reduced representation bisulfite sequencing analysis. In total, 166 differentially methylated cytosines were identified in the sperm from treatment versus control rams. Nine genes were found to be differentially expressed in embryos produced from treatment versus control rams, and seven differentially methylated cytosines in the sperm were found to be highly correlated with gene expression in the embryos. Our results demonstrate that sperm methylation differences induced by diet may influence fetal programming. [ABSTRACT FROM AUTHOR]

We examined the effects of dynamic feeding low- and high-methionine diets on the transcriptional level of glucose and lipid metabolism-related genes in the liver of laying hens. A total of 180 laying hens (Brown Hy-line, 41 wk old) were exposed to 16 h of light and 8 h of darkness with lights on at 06:00 h local time (Zeitgeber time [ZT] 0) and allocated into 3 equal groups with 6 replicates. The control group was fed a 0.30% methionine diet. The low-high (LH) group was fed 0.27% methionine diet at ZT1.5 and 0.33% methionine diet at ZT8.5. The feeding regime in high-low (HL) group was opposite to that of the LH group. After 10 wk, a total of 108 hens (6 hens/group/time point) were randomly and equally selected for further analysis. Blood and liver tissues were collected at ZT21.5, ZT1.5, ZT5.5, ZT9.5, ZT13.5, and ZT17.5. The results showed that the serum ALP activity in the HL group was the highest at ZT9.5 and ZT13.5, and that the serum glucose content in the HL group was lowest at ZT21.5 compared to the other 2 groups (P < 0.05). The mesors, amplitudes, and acrophases of the cosine curves for the CLOCK, BMAL1, CRY1, PER2, and PER3 genes were altered in the LH and HL groups. G6PC3, PCK2, GPAT, INSIG2, FASN, ACACA, ACOX1, HMGCR, LDLR, and PPARA expression in the liver were affected by the feeding regime at some time point (P < 0.05). Two-way analysis of variance comparisons showed some significant effects of time on the mRNA expression of G6PC3, G6PC2, PCK2, FBP1, FBP2, GCK, GYS2, FASN, GPAT, HMGCR, LDLR, ACC, SREBP2, and INSIG1 (P < 0.05). Moreover, different feeding regimes significantly affected the expression of FASN, GPAT, HMGCR, LDLR, ACACA, SREBP1, and INSIG1 (P < 0.05). In conclusion, dynamical feeding low- and high-methionine diets affected the variation of serum ALP and glucose levels, as well as the mRNA expression of circadian clock- and glucose and lipid metabolism-related genes in the liver of laying hens. [ABSTRACT FROM AUTHOR]

The effect of methionine on bone remodeling parameters of young and adult male rats Vistar was studied. The introduction of excess methionine (250 mg / kg for 21 days) in the diet raises the physiological regeneration of bone tissue in young rats. Increasing their alkaline phosphanase activity in bone tissue testifies to the domination of the osteosynthetic phase of osteogenesis relative to osteolytic. Such a reaction is typical for increasing the number of active osteoblasts or increasing the sensitivity of their receptors. Unlike young animals, in adult male rats, age-related bone tissue changes are manifested in the domination of the osteolytic phase. The obtained results testify to the disease-dependent differences in the effect of the same factor dose on the processes of physiological regeneration and the organic matrix of bone tissue rats in males, which should be taken into account when using medicinal preparations. [ABSTRACT FROM AUTHOR]

Abstract This study was to explore the effect and mechanisms of anti- human gastric cancer by MENK in vitro and in vivo. The results showed in MENK-treated xenograft tissue, the percentage of M2-type macrophages decreased while M1-type macrophages increased. MENK increased the expression of M1-related cytokine TNF-α and attenuated the expression of M2-related cytokine IL-10 expression. MENK upregulated the expression of opioid receptor (OGFr), while it inhibited HGC27 and SGC7901 cells through blocking PI3K/AKT/mTOR signal pathway in vitro and in vivo. These effects of MENK could be cancelled when OGFr was knockdown. This indicates that binding to OGFr by MENK appears to be essential for the anti- GC cells. Therefore, it is concluded that MENK might skew macrophage toward M2 phenotype from M1 phenotype within tumor and induce cells apoptosis though blocking OGFr/PI3K/AKT/mTOR signaling pathway. Highlights • MENK could inhibit the growth of human gastric cancer (GC). • MENK exerts an antitumor activity though reversing TAMs polarization from M2 to M1. • OGFr has been proven to as a functional target for MENK to regulate proliferation and apoptosis of GC cells. • MENK inhibits proliferation and induces apoptosis via OGFr/PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract The goal of this work was to investigate how MENK could regulate the functions of CD8+T cells and to explore the relationship between this regulation and opioid receptor expression. Our results showed that the opioid receptors presented on the cell menbrane of CD8+T cells were MOR and DOR. MENK promoted the expression of opioid receptors as well as the elevation of the surface molecules such as CD28, PD-1, CTLA-4 and FasL and intracellular granzyme B. Selectively blocking the MOR by CTAP or DOR by NTI could result in inhibition of the corresponding CD8+T cells proliferation and the expressions of surface molecules. In addition, non-selectively blocking both MOR and DOR by NTX could further impair the functions and proliferation of CD8+T cells. Our currently data indicated that MENK could play a vital role in immune functions via precise regulation to subunits of opioid receptors. Highlights • MENK enhanced the proliferation and functions of CD8+T cells through up-regulating mu and delta opioid receptors. • This effect of MENK could be cancelled while one or both of the receptors would be blocked. • MENK could play a vital role in immune functions via precise regulation to subunits of opioid receptors. [ABSTRACT FROM AUTHOR]

Pregnancy and early life are critical periods during which environmental factors such as nutrition can affect development. Rumen-protected methionine (Met; RPM) supplementation during the prepartum period improves not only performance but immune responses in dairy cows. We investigated the effects of enhanced maternal supply of Met via feeding RPM on whole-blood in vitro lipopolysaccharide (LPS; 0, 0.01, or 5 μg/mL of blood) challenge and targeted microRNA and mRNA abundance in calf blood polymorphonuclear leukocytes (PMNL). Calves (n = 12/maternal diet) born to cows fed RPM at 0.08% of diet dry matter (DM)/d (MET) for the last 21 ± 2 d before calving or fed a control diet with no added Met (CON) were used. The PMNL were isolated at birth (before colostrum feeding) and d 1 (24 h after colostrum intake), 14, 28, and 50 of age. Maternal blood was collected at −10 ± 1.3 d relative to calving. Cows in the MET group had greater DM intake and lower prepartal haptoglobin concentration. In CON cows, haptoglobin was positively correlated with proinflammatory and host-defense mRNA abundance in CON calves. Except for NOS2 and NFE2L2, abundance of CASP8, MPO, ZBP1, and TNF was lower at birth in MET calves. Interleukin 1β concentration in response to LPS challenge in CON and MET calves was greatest at birth, underscoring the role of this cytokine for lymphocyte activation. Compared with 1 d of age, the interleukin-1β response to incremental doses of LPS was greater at 14 through 28 d, suggesting that the neonatal calf can mount a robust response to inflammatory stimuli. Greater abundance in CON calves of NOS2, CADM1, and TLR2 coupled with lower SELL from 1 through 50 d of age suggested a chronic activation of the PMNL. There was a marked upregulation over time of MIR125b, MIR146a, MIR155, and MIR9 in both CON and MET calves, suggesting that these microRNA could affect gene transcription associated with differentiation and inflammatory function in PMNL. Regardless of maternal diet, the gradual downregulation of MIR223 (the most abundant microRNA in PMNL) is in line with the progressive increase over time in the proinflammatory signature of the PMNL. Data revealed the potential for maternal supply of Met during late pregnancy through either greater DM intake or Met to elicit some changes in PMNL function during early postnatal life, partly through changes in mRNA expression encompassing cell adhesion and chemotaxis, oxidative stress, Toll-like receptor signaling, and Met metabolism. [ABSTRACT FROM AUTHOR]

Dietary methionine (met) is reported to enhance antibody production and boost cell-mediated immunity in chickens. Methionine deficiency has been shown to affect the development of the lymphoid organs and the generation of antibodies in chickens. This study is designed to investigate the effects of met deficiency on IgA+ B cells and immunoglobulins (sIgA, IgA, IgG and IgM) for a 6 week period in the duodenum and jejunum of Cobb broiler chicken using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) techniques. The results of the study showed that the IgA+ B cell count reduced significantly in the met deficiency group compared to the control group (P<0.05 or P<0.01). The contents of sIgA, IgA, IgG and IgM in the met deficiency group were significantly decreased (P<0.05 or P<0.01), especially at 28 and 42 days of age. It can be concluded that met deficiency exerts significant effects on the humoral immune system of intestinal mucosa. This study has provided valuable experimental insight which could be useful for future studies on the function of met in the intestine of humans and other animals. [ABSTRACT FROM AUTHOR]

The objective was to examine the effect of different dietary zinc sources on reproduction of male Japanese quail. A total of 512 quail chicks (day-old) were divided into four groups with four replications for a period of 42 days. After this period, excess chicks were removed to attain the ratio of one male to three females and 16 quail in each subgroup. At 52 to 60 d of age, the eggs were collected and incubated. The basal diet (control) contained no zinc and the other three experimental diets were supplemented with 25 and 50 mg/kg zinc from zinc oxide (ZnO), zinc oxide nanoparticles (ZnONP) and zinc-methionine (Zn-Met) for 1 to 35 and 36 to 60 days, respectively. On day 42, two males from each replicate were euthanized. Males from the ZnO and Zn-Met treatments had an increase ( P  < 0.05) in seminiferous tubule diameters (STD) and germinal epithelium thickness (GET) compared with the control and ZnONP treatments. Cloacal gland index (CGI) was greatest ( P  < 0.05) for the Zn-Met compared with the other groups. Testosterone concentration was greater ( P  < 0.05) in the ZnO and Zn-Met compared with the other groups. Addition of Zn-Met to the diet enhanced ( P  < 0.05) fertility, hatchability and hatched chick weight compared with the other groups. Early and late embryonic death was greater ( P  < 0.05) in the control and ZnONP groups, respectively, compared with the other groups. This study indicated that supplementing diets with the Zn-Met source improves male Japanese quail reproductive performance and hatchability traits while zinc oxide nanoparticles have detrimental effects on male Japanese quail reproduction and reduces hatchability. [ABSTRACT FROM AUTHOR]

An important goal of rice cultivar development is improvement of protein quality, especially with respect to essential amino acids such as methionine. With the goal of increasing seed methionine content, we generated Oryza sativa ssp. japonica cv. Taipei 309 transgenic lines expressing a feedback-desensitized CYSTATHIONINE GAMMA-SYNTHASE from Arabidopsis thaliana ( AtD-CGS ) under the control of the maize ubiquitin promoter. Despite persistently elevated cystathionine gamma-synthase (CGS) activity in the AtD-CGS transgenic lines relative to untransformed Taipei, sulfate was the only sulfur-containing compound found to be elevated throughout vegetative development. Accumulation of methionine and other sulfur-containing metabolites was limited to the leaves of young plants. Sulfate concentration was found to strongly and positively correlate with CGS activity across vegetative development, irrespective of whether the activity was provided by the endogenous rice CGS or by a combination of endogenous and AtD-CGS. Conversely, the concentrations of glutathione, valine, and leucine were clearly negatively correlated with CGS activity in the same tissues. We also observed a strong decrease in CGS activity in both untransformed Taipei and the AtD-CGS transgenic lines as the plants approached heading stage. The mechanism for this downregulation is currently unknown and of potential importance for efforts to increase methionine content in rice. [ABSTRACT FROM AUTHOR]

The study was conducted to investigate whether high-dose zinc methionine (Zn-Met) affected the safety of laying hens, including laying performance, hematological parameters, serum chemical parameters, organ index, and histopathology. A total of 540 20-week-old Hy-Line White laying hens was randomly allocated to 6 groups with 6 replicates of 15 birds each. Birds were fed diets supplemented with 0 (control), 70, 140, 350, 700, or 1,400 mg Zn/kg diet as Zn-Met. The experiment lasted for 8 wk after a 2-week acclimation period. Results showed that dietary supplementation with 70 or 140 mg Zn/kg diet as Zn-Met significantly increased average daily egg mass (ADEM), laying rate (LR), and feed conversion ratio (FCR) (P < 0.05) and lowered broken and soft-shelled egg ratio (BSER) (P < 0.05) in comparison with the control group; no significant differences were detected among hens fed with 0, 350, or 700 mg Zn/kg as Zn-Met (P > 0.05); hens administered 1,400 mg Zn/kg showed a significant increase in BSER and remarkable decreases in ADEM, LR, and FCR (P < 0.001). There were no significant differences among hens receiving 0, 70, 140, 350, or 700 mg Zn/kg as Zn-Met in serum chemical parameters (P > 0.05); supplementation with 1,400 mg Zn/kg as Zn-Met remarkably elevated the concentrations of serum total bilirubin (TBILI), glucose (GLU), uric acid (UA), and creatinine (CRE) (P < 0.001), and enhanced activities of serum glutamic oxalacetic transaminase (GOP) and alkaline phosphatase (AKP) (P < 0.001) compared with the control group. No significant histopathological changes were found in hens administered 0, 70, 140, 350, or 700 mg Zn/kg as Zn-Met, while significant histological lesions were observed in the heart, liver, lung, and kidney tissues of hens receiving 1,400 mg Zn/kg as Zn-Met. No significant differences were detected in hematological parameters or organ index (P > 0.05). In conclusion, a nominal Zn concentration of 700 mg/kg as Zn-Met is considered to be no-observed-adverse-effect level following daily administration to hens for 56 days. [ABSTRACT FROM AUTHOR]

Methionine is an essential/indispensible amino acid nutrient required by adult and larval honey bees ( Apis mellifera L. [Hymenoptera: Apidae]). Bees are unable to rear broods on pollen deficient in methionine, and reportedly behaviorally avoid collecting pollen or nectar from florets deficient in methioinine. In contrast, it has been demonstrated that methionine is toxic to certain pest insects; thus it has been proposed as an effective biopesticide. As an ecofriendly integrated pest management agent, methionine boasts a novel mode of action differentiating it from conventional pesticides, while providing non-target safety. Pesticides that minimize collateral effects on bees are desirable, given the economic and ecological concerns about honey bee health. The aim of the present study was to assess the potential impact of the biopesticide methionine on non-target adult and larval honey bees. Acute contact adult toxicology bioassays, oral adult assessments and chronic larval toxicity assessments were performed as per U.S. Environmental Protection Agency (EPA) requirements. Our results demonstrated that methionine fits the U.S. EPA category of practically nontoxic ( i.e. lethal dose to 50% mortality or LD 50 > 11 µg/bee) to adult honey bees. The contact LD 50 was > 25 µg/bee and the oral LD 50 was > 100 µg/bee. Mortality was observed in larval bees that ingested DL-methionine (effective concentration to 50% mortality or EC 50 560 µg/bee). Therefore, we conclude that methionine poses little threat to the health of the honey bee, due to unlikely exposure at concentrations shown to elicit toxic effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of methionine (Met) deficiency on antioxidant functions (in the duodenal, jejunal and ileal mucosa) and apoptosis in the duodenum, jejunum and ileum of broiler chickens. A total of 120 one-day-old Cobb broilers were divided into two groups and fed a Metdeficient diet and a control diet, respectively, for six weeks. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), the ability to inhibit hydroxyl radicals, and glutathione (GSH) content were significantly decreased in the Met-deficient group compared to the control. In contrast, malondialdehyde (MDA) content was significantly higher in the Met-deficient group. As measured by terminal deoxynucleotidyl transferase 2’-deoxyuridine 5’- triphosphate dUTP nick end-labelling (TUNEL) and flow cytometry (FCM), the percentages of apoptotic cells were significantly increased. In conclusion, dietary Met deficiency can cause oxidative stress and then induce increased apoptosis in the intestine. Oxidative stress contributes to intestinal apoptosis. This results in the impairment of local intestinal mucosal immunity due to oxidative stress and apoptosis in the small intestine. The results of this study provide new experimental evidence for understanding the negative effects of Met deficiency on mucosal immunity or the functions of other immune tissues. [ABSTRACT FROM AUTHOR]

An 8-week feeding trial was conducted to evaluate the effects of three dietary methionine (Met) sources [ dl-Met, coated-Met, and a methionine hydroxy analogue calcium salt (MHA-Ca)] for Chinese soft-shelled turtle ( Pelodiscus sinensis). Triplicate groups of juvenile turtles (initial weight 3.48 ± 0.03 g) were fed twice per day at 3% of body weight with positive control diet (T1, 46% protein and 46% fish meal, FM), negative control diet (T2, 43% protein and 23% FM), or three other test diets supplemented with either 0.2% coated-Met (T3), 0.125% MHA-Ca (T4), or 0.1% dl-Met (T5) to the T2 basal formulation, respectively. The feeding trial was conducted in 15 350-L plastic containers with three replicates per dietary treatment. The results showed that the highest and lowest percentage weight gain (1023.5 ± 18.2 versus 882.1 ± 14.5%) and feed efficiency (87.2 ± 0.94 versus 81.4 ± 0.4%) were observed in turtles fed the T1 and T2 diet ( P < 0.05), respectively. Significant improvement in weight gain was observed in turtles fed diets with Met supplementation, irrespective of source, compared with turtles fed the T2 diet. It was observed that dietary MHA-Ca had similar efficacy compared with dl-Met in terms of growth performance and feed utilization efficiency of the turtles ( P > 0.05). Protein utilization efficiency was significantly higher in turtles fed T4 or T5 diet compared to the T2 diet. Whole body protein content (17.0 to 17.4% on a wet weight basis) in turtles fed with Met-added diets was comparable to those of turtles fed the T1 diet which were significantly higher compared to T2-fed turtles. Antioxidant defense system enzymes, superoxide dismutase, and glutathione peroxidase showed the highest activity, 658.8 ± 17.9 U/mL and 642.8 ± 17.5 μmol/L, respectively, in the serum of turtle fed the MHA-Ca supplemented diet and was significantly higher compared to turtles fed the T2 or T3 diet. The present results showed that P. sinensis are able to effectively use added MHA-Ca and dl-Met in low protein and low FM diets to enhance growth, feed utilization efficiency, nitrogen retention, and antioxidant defense system enzyme activities. [ABSTRACT FROM AUTHOR]

Abstract: This study was performed to determine the dietary methionine requirements and its effects on growth performance, plasma and hepatic metabolites for juvenile silver catfish. The fish (initial weight = 3.26 ± 0.3 g) were distributed in 24 experimental units (35 fish each). Six diets were formulated with increasing levels of methionine (09, 16, 23, 30, 37 and 44 g/kg protein diet). Each diet was distributed randomly to the groups, with four replicates fed twice daily to apparent satiation for 15 weeks. Methionine levels influenced in body composition (moisture and ash), and submit effect on liver metabolism and plasma. The relative weight gain (RWG) and specific growth rate (SGR) increased with highest levels of methionine to 30 g/kg protein in the diet, thereafter maintaining a nearly constant level of 1.9 g/kg cystine in the protein diet. The protein retention coefficient (PRC) also increased with increasing levels of up to 23 g/kg protein diet, thereafter maintaining a constant level of 1.9 g/kg cystine protein diet until beginning to decrease at a level of 44 g/kg protein diet. In conclusion, methionine is an essential amino acid for the growth of juvenile silver catfish and exhibits an efficient capacity when provided as a synthetic amino acid. Based on the RWG and SGR data, the methionine requirement of juvenile silver catfish was estimated at 34.42 and 35.85 g/kg of the CP or 12.74 g/kg and 13.26 g/kg of the diet respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effects of different sources and levels of methionine (Met) on Heat shock proteins HSP70 expression and protein carbonylation in liver, HSP70 expression and malondialdehyde ( MDA) concentration in intestine under heat stress conditions during summer. A total of 720 (4 days old) Peking ducks were placed 20 per pen into six replicates for each of the six treatments with a 2 × 3 factorial arrangement, such that two sources of Met ( DL-methionine [ DLM] and DL-2-hydroxy-4-methylthiobutyrate [ HMTBA] were supplemented at three different levels (0.05%, 0.20%, or 0.35% on as-fed basis respectively). The experiment was divided into a starter (day 4-16) and a grower (day 17-35) period. Diet supplemented with 0.35% Met significantly up-regulated the HSP70 mRNA expression in duodenum, jejunum and ileum on day 16 and 35 as well as in liver on day 35 ( p < .05) of ducks. HMTBA-supplemented diets increased the HSP70 mRNA expression in duodenum, jejunum, ileum and liver on day 35 ( p < .01). An increased MDA concentration was detected in jejunum of birds in 0.35% DLM-supplemented treatment on day 16 ( p < .05). And decreased protein carbonylation concentration was found in DLM-supplemented treatment on day 16 ( p < .01). The birds fed with 0.35% Met supplemental diet displayed lower hepatic protein carbonylation on day 16 ( p < .05). In conclusion, supplementation of 0.35% Met in the duck diet showed up-regulated HSP70 expression in small intestine and liver, which may provide new perspective to the mechanism of Met function. At the same time, DLM supplemented in diet may ameliorate oxidative status of liver, while HMTBA supplementation may partially improve the intestinal oxidative status of Peking ducks. [ABSTRACT FROM AUTHOR]

The giant anteater ( Mymercophaga tridactyla) is a highly specialized insectivore for which nutrient requirements are not clearly established, making diet formulation challenging for this species. Multiple clinical reports suggest anteaters have an obligate dietary taurine ( TAU) requirement. Sulphur amino acid ( SAA) metabolism in adult anteaters was evaluated using noninvasive methods to measure TAU synthesis potential from dietary methionine ( MET) and a basal diet containing on a dry matter ( DM) basis 1.7 mg TAU/kg DM and 6.9 g MET/kg DM. Urinary equilibrium times for TAU excretion were determined by feeding the basal diet with or without 1.5 g/kg DM supplemental TAU (crossover design; n = 4). Effects of supplemental dietary TAU (1.7, 2.0, 2.4, 2.7, 3.0, 3.3 g/kg DM) or MET (6.9, 9.0, 11.2 g/kg DM) on urinary TAU were evaluated (randomized block trials; n = 5 or 4 respectively). All urinary values ( TAU, MET, unbound inorganic sulphate) were normalized to creatinine ( CRT). Results indicate urinary TAU equilibrium in anteaters requires at least 2 weeks of feeding. Urinary ratio of TAU to CRT ( TAU: CRT) increased as dietary TAU content increased from 1.7 to 3.0 g/kg DM, consistent with renal homoeostatic modulation of TAU excretion. Our data indicate that TAU needs were met by TAU in the basal diet or by de novo synthesis. Supplemental MET resulted in ~five- to eightfold increases in urinary TAU: CRT excretion, further supporting existence of mechanisms for TAU synthesis from dietary SAA in anteaters. Adult anteaters appear able to synthesize TAU when diets contain adequate SAA, but dietary TAU may be critical if protein intakes are low or of poor quality. This study may provide guidance on choice of domestic canids vs. felids as suitable physiologic models for improved nutrition in giant anteaters, and also outlines a noninvasive method for assessing TAU status/metabolism that may be useful across species. [ABSTRACT FROM AUTHOR]

In the present work, we evaluated the effect of gestational hypermethioninemia on locomotor activity, anxiety, memory, and exploratory behavior of rat offspring through the following behavior tests: open field, object recognition, and inhibitory avoidance. Histological analysis was also done in the brain tissue of pups. Wistar female rats received methionine (2.68 μmol/g body weight) by subcutaneous injections during pregnancy. Control rats received saline. Histological analyses were made in brain tissue from 21 and 30 days of age pups. Another group was left to recover until the 30th day of life to perform behavior tests. Results from open field task showed that pups exposed to methionine during intrauterine development spent more time in the center of the arena. In the object recognition memory task, we observed that methionine administration during pregnancy reduced total exploration time of rat offspring during training session. The test session showed that methionine reduced the recognition index. Regarding to inhibitory avoidance task, the decrease in the step-down latency at 1 and 24 h after training demonstrated that maternal hypermethioninemia impaired short-term and long-term memories of rat offspring. Electron microscopy revealed alterations in the ultrastructure of neurons at 21 and 30 days of age. Our findings suggest that the cell morphological changes caused by maternal hypermethioninemia may be, at least partially, associated to the memory deficit of rat offspring. [ABSTRACT FROM AUTHOR]

Environmental stresses are increasing over time adversely affecting crop productivity. To face these stresses, plants adopt endogenous mechanisms, but they are not enough in most cases. Therefore, the effect of exogenous application of proline, silicon (Si) or methionine on growth and yield criteria, leaf physio-biochemical properties and leaf anatomical structure of cowpea plants grown under three levels of water deficit (W 0 ; 60, W 1 ; 40 and W 2 ; 20% of soil water holding capacity) was investigated. The water level W 0 was adequate to optimum cowpea plant growth and specified as a control. Results obtained indicated that growth criteria (i.e., shoot dry weight, plant height, leaf area and number of branches per plant), yield characteristics (i.e., dry seed weight and biological yield per plant, and 100-seed weight), contents of leaf chlorophylls a and b , total carotenoids, shoot and seed nutrients (i.e., N, P and K), and leaf relative water content and membrane stability index were significantly decreased, while activity of leaf antioxidant enzymes such as peroxidase (POX), superoxide dismutase (SOD) and catalase (CAT), content of leaf proline and electrolyte leakage, and shoot Si were significantly increased under water deficit stress (W 1 and W 2 ) conditions compared to the control (W 0 ). However under water deficit stress, foliar application of proline, Si or methionine seemed to overcome the harmful effects of water deficit stress, at varying degrees, on the abovementioned cowpea plants characters, which were improved, compared to the corresponding controls. The Si was the most helpful one, where it increased growth criteria (i.e., shoot dry weight, plant height, leaf area and number of branches per plant), yield characteristics (i.e., dry seed weight and biological yield per plant, and 100-seed weight), contents of leaf chlorophylls a and b , total carotenoids, shoot and seed nutrients (i.e., N, P and K), and leaf relative water content and membrane stability index, and further increased shoot Si content and leaf antioxidant enzyme activities of cowpea plants compared to those of either proline or methionine application. For leaf anatomical features, the width of midvein and xylem, and the thickness of midvein, phloem and xylem tissues, and palisade and spongy tissues of leaf blade were decreased with increasing the water deficit stress; however, foliar spray of Si improved all histological features compared to those of untreated plants. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse the effects of different dietary methionine (Met) concentrations on the mechanisms of fish muscle growth (hyperplasia and hypertrophy) by using cellular and molecular approaches. Three plant-based diets differing by their Met level (MD, Met-deficient; MC, Met-control, corresponding to established Met requirement; MH, Met-high) were fed to rainbow trout juveniles for 12 weeks. Met deficiency led to a reduced somatic growth right from the first 3 weeks of feeding onwards, while feeding the MH-diet led to an increased body growth in the 6 last weeks of feeding. The protein gain of the juveniles increased with dietary Met content. The protein retention efficiency of the MD-fed juveniles was half that of the MC- and MH-fed juveniles which were statistically similar. The changes induced by MD- and MH-feeding at muscle molecular and cellular levels were different. Compared to control, dietary Met deficiency altered the expression of myogenic, muscle growth- and metabolism-related genes by increasing Myf5, MyoD1, Mrf4, Mef2a, βact, CathD, GSTπ and TNFα expressions and decreasing Col1α1 and IGF1 expressions, whereas a high level of dietary Met decreased Pax7a2, Mef2c, βact, CathD, GDH2 and NF-κB expressions. The Met-control fed fish were discrimated according to HGF, Pax7a1 and Pax7a2 expressions. Dietary Met level thus acted on the expression of genes regulating specific transition points of myogenesis, and affected the expression of muscle structural genes and growth factors involved in satellite cell activation and muscle growth. Molecular results suggested that MD-diet favours satellite cell return to quiescence, while MC-diet favours satellite cell activation and MH-diet myogenic differentiation. At cellular level, the muscle total cross-sectional area of the juveniles fed the MD-diet was 28% lower than that of the juveniles fed the MC-diet despite a similar total number of white muscle fibres, and the number of white muscle fibres with a large diameter was lower in MD-fed fish than in MC-fed ones. The muscle total cross-sectional area of the juveniles fed the MH-diet was 32% higher than that of the juveniles fed the MC-diet, their total number of white muscle fibres 25% higher, and their number of white muscle fibres with a large diameter similar. Increasing dietary methionine above established requirement thus promotes white muscle hyperplasia and muscle growth in rainbow trout juveniles, while methionine deficiency dysregulates the expression of myogenic and muscle growth-related genes and impairs white fibre hypertrophy. Statement of relevance Determining the effects of dietary methionine levels on muscle growth mechanisms will help develop low fish meal feeds. [ABSTRACT FROM AUTHOR]

We conducted two trials to evaluate the methionine-sparing effects of choline (Chol) and betaine (Bet), and their effects on growth performance and blood antioxidative potential in heat-stressed broiler chickens fed methionine (Met)-deficient diets. We used 360 1-day-old broiler chicks (Ross 308) in a completely randomized study with 5 replicate pens of 12 birds each. After Day 21, we raised the temperature to 35±3℃using an automated air-forced heater for 12 hours/day from 8 am to 8 pm to expose the birds to heat stress. In Trial 1, the treatments comprised a negative control (control-; 1200 mg/kg Met-deficient), a positive control (control+; recommended level of Met), 280Chol (control- plus 280 mg/kg Chol), 560Chol (control- plus 560 mg/kg Chol), 320Bet (control- plus 320 mg/kg Bet), and 640Bet (control- plus 640 mg/kg Bet); and in Trial 2, the treatments comprised a negative control (control-), a positive control (control+), 140Chol+160Bet (control- plus 140 mg/kg Chol and 160 mg/kg Bet), 280Chol+160Bet (controlplus 280 mg/kg Chol and 160 mg/kg Bet), 140Chol+320Bet (control- plus 140 mg/kg Chol and 320 mg/kg Bet), and 280Chol+320Bet (control- plus 280 mg/kg Chol and 320 mg/kg Bet). Compared with the other treatments, the feed conversion ratio (FCR) was improved in the 280Chol and control+ groups in Trials 1 and 2 (P＜0.05). In Trial 2, the cost of meat production for the entire experimental period (1-42 days) was higher in the 140Cho+320Bet-fed birds than in the other birds (P＜0.05), except the control- birds. Supplementing diets with 280 mg/kg of Chol significantly reduced the serum concentration of uric acid compared with the control+ group (P＜0.05). Our results indicate that the Met requirements of heat-stressed broiler chickens can be reduced by 20% (1200 mg/kg) if the diet is supplemented with 280 mg/kg of Chol. [ABSTRACT FROM AUTHOR]

The first committed step of the shikimate pathway is catalyzed by a metalloenzyme 3-deoxy- d -arabino-heptulosonate-7-phosphate synthase (DAH7PS), which exhibits vulnerability to the oxidative stress. DAH7PS undergoes inactivation in multiple ways in the presence of redox metal, H 2 O 2 , and superoxide. The molecular mechanism and susceptibility of its inactivation might differ in different organisms and are presently unclear. In the present work, we have cloned, expressed and purified a DAH7PS from Providencia alcalifaciens (PaDAH7PS). The oligomeric state and effect of redox metal treatment on its stability were analyzed through the size exclusion chromatography. The FTIR, MALDI-TOF/TOF-MS studies revealed that methionine residues were modified to methionine sulfoxide in PaDAH7PS. During oxidation, PaDAH7PS is altered into partially folded protein and unfolded states as determined by CD and Fluorescence studies. A significant loss in enzymatic activity of PaDAH7PS was determined and the formation of amorphous aggregates was visualized using AFM imaging and also confirmed by ThT binding based assay. This is the first report where we have shown a hexameric DAH7PS and the methionine residues of PaDAH7PS get oxidize in the presence of oxidative stress. The partially folded and unfolded oligomeric states with high β-content of PaDAH7PS might be the critical precursors for aggregation. [ABSTRACT FROM AUTHOR]

The precursor homocysteine is metabolized either through the methionine cycle to produce methionine or through the transsulfuration pathway to synthesize cysteine. Alternatively, cysteine can be obtained through uptake of its oxidized form, cystine. Many cancer cells exhibit methionine dependency such that their proliferation is impaired in growth media in which methionine is replaced by homocysteine. We showed that oncogenic PIK3CA and decreased expression of SLC7A11, a gene that encodes a cystine transporter also known as xCT, correlated with increased methionine dependency in breast cancer cells. Oncogenic PIK3CA was sufficient to confer methionine dependency to mammary epithelial cells, partly by decreasing cystine uptake through the transcriptional and posttranslational inhibition of xCT. Manipulation of xCT activity altered the proliferation of breast cancer cells in methionine-deficient, homocysteine-containing media, suggesting that it functionally contributed to methionine dependency. We propose that concurrent with decreased cystine uptake through xCT, PIK3CA mutant cells use homocysteine through the transsulfuration pathway to synthesize cysteine. Consequently, less homocysteine is available to produce methionine, contributing to methionine dependency. These results indicate that oncogenic PIK3CA alters methionine and cysteine utilization, partly by inhibiting xCT to contribute to the methionine dependency phenotype in breast cancer cells. [ABSTRACT FROM AUTHOR]

This study investigated the hypothesis that dietary concentrations of methionine (Met), as a precursor of cysteine which is a constituent of glutathione ( GSH), affect tissue antioxidant concentrations and the antioxidant defence system in pigs. Forty-five piglets (DanZucht × Pietrain) were allotted to three groups of similar mean body weight (11.0 ± 0.9 kg). The basal diet was composed of barley, wheat, corn starch, soybean oil, sucrose, cellulose and a mineral supplement with suboptimal concentrations of Met and was supplemented with dl-Met to reach 0.16%, 0.20% and 0.24% of dietary Met and 0.40%, 0.44% and 0.48% of dietary Met and cysteine in groups 0.16, 0.20 and 0.24 respectively. After 3 weeks, at slaughter, samples of liver, jejunum mucosa and plasma were collected. Feed intake and weight gains increased and feed:gain ratio decreased when dietary Met concentrations increased. The Trolox equivalent antioxidant capacity ( TEAC), concentrations of GSH and thiobarbituric acid reactive substances ( TBA- RS) and the activity of the glutathione peroxidase ( GPx) in liver and jejunum mucosa were similar in all groups (p > 0.05). Relative mRNA concentrations of selected target genes of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the master regulator of the antioxidant response, and of the nuclear factor 'kappa-light-chain-enhancer' of activated B-cells ( NF- κB), the master regulator of inflammation, were largely unaffected both in jejunum and liver. In conclusion, inflammation- and oxidative stress-related pathways on the molecular level, and concentrations of lipid peroxidation products, of antioxidants and of enzymes involved in the antioxidant defence system were mostly unaffected by dietary Met concentration in gut and liver. These findings suggest that suboptimal dietary Met concentrations did not influence the antioxidant defence system of gut and liver in healthy piglets. [ABSTRACT FROM AUTHOR]

Three experiments were conducted to investigate the interaction between zinc methionine (ZnM) and laminarin ( LAM) on piglet growth performance and intestinal health post-weaning. Experiment 1 was designed as 2 × 2 factorial with four treatments [ n = 8, weaning age ( WA) 24 days, live weight ( LW) 7.15 kg]: (i) basal diet ( BD); (ii) BD + 500 mg/kg ZnM; (iii) BD + 300 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 300 mg/kg LAM. There was an interaction (p < 0.05) between LAM and ZnM. Pigs that were offered the LAM diet had a similar performance to the BD. However, when combining LAM with ZnM, pigs had reduced average daily gain ( ADG), gain-to-feed ratio (G:F) and LW at slaughter at day 8 post-weaning compared to the ZnM. Both LAM and ZnM improved the small intestinal morphology of the pigs at day 8 post-weaning. Experiment 2 was designed as 2 × 2 factorial with four dietary treatments ( n = 9, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 500 mg/kg ZnM; (iii) BD + 175 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 175 mg/kg LAM. The ADG and average daily feed intake were improved between day 0 and 31 PW when pigs were offered a LAM diet (p < 0.01). Faecal scores were reduced between day 0 and day 31 post-weaning with ZnM (p < 0.001). Experiment 3 consisted of four dietary treatments ( n = 10, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 3300 mg/kg zinc oxide (ZnO); (iii) BD + 500 mg/kg ZnM; and (iv) BD + 175 mg/kg LAM. Pigs that were offered the ZnO diet had an increased ADG compared to the BD or ZnM diets (p < 0.01). Pigs that were offered the LAM diet had increased ADG compared to the ZnM diet (p < 0.05). Faecal scores were reduced between day 0 and day 31 PW with ZnM or ZnO supplementation (p < 0.001). In conclusion, the inclusion of 175 mg/kg LAM and ZnO improved ADG while both ZnO and ZnM reduced the faecal scores post-weaning. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard) and deficiency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight) were divided into three groups: control (n=8), methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7) and methionine-enriched vitamin-deficient (Meth+Vit-, 7.7 g of methionine/kg chow, deficient in folate, pyridoxine and cobalamine - 0.08, 0.01 and 0.01 mg/kg, n=8). All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM) test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM) were significantly reduced following 30 days of methionine nutritional overload (p<0.05, p<0.05 and p<0.01, respectively). A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p<0.01). The decline in total exploratory activity associated with vitamin deficiency was significant compared to the Meth+ group (p<0.05). The results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-deficient diet could be attributed to an anxiogenic effect of hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

The low methionine content in plant-based diets is a major limiting factor for feed utilization by animals. However, the molecular consequences triggered by methionine deficiency have not been well characterized, especially in fish species, whose metabolism is unique in many aspects and important for aquaculture industry. In the present study, the primary muscle cells of turbot (Scophthalmus maximus L.) were isolated and treated with or without methionine for 12 h in culture. The responses of nutrient sensing pathways, the proteomic profiling of metabolic processes, and the expressions of key metabolic molecules were systematically examined. Methionine deprivation (MD) suppressed target of rapamycin (TOR) signaling, activated AMP-activated protein kinase (AMPK) and amino acid response (AAR) pathways. Reduced cellular protein synthesis and increased protein degradation by MD led to increased intracellular free amino acid levels and degradations. MD also reduced glycolysis and lipogenesis while stimulated lipolysis, thus resulted in decreased intracellular lipid pool. MD significantly enhanced energy expenditure through stimulated tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Collectively, our results identified a comprehensive set of transcriptional, proteomic, and signaling responses generated by MD and provided the molecular insight into the integration of cell homeostasis and metabolic controls in fish species. [ABSTRACT FROM AUTHOR]

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases. [ABSTRACT FROM AUTHOR]

The present most common image diagnostic tracer in clinical practice for glioma is 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for brain tumors diagnosis and prognosis. PET is a promising molecular imaging technique, which provides real-time information on the metabolic behavior of the tracer. The diffusive nature of glioblastoma (GBM) and heterogeneity often make the radiographic detection by FDG-PET inaccurate, and there is no gold standard. FDG-PET often leads to several controversies in making clinical decisions due to their uptake by normal surrounding tissues, and pose a challenge in delineating treatment-induced necrosis, edema, inflammation, and pseudoprogression. Thus, it is imperative to find new criteria independent of conventional morphological diagnosis to demarcate normal and tumor tissues. We have provided proof of concept studies for 11C methionine-PET (MET-PET) imaging of gliomas, along with prognostic and diagnostic significance. MET-PET is not widely used in the United States, though clinical trials from Japan and Germany suggesting the diagnostic ability of MET-PET imaging are superior to FDG-PET imaging for brain tumors. A major impediment is the availability of the onsite cyclotron and isotopic carbon chemistry facilities. In this article, we have provided the scientific rationale and advantages of the use of MET-PET as GBM tracers. We extend our discussion on the expected pitfalls of using MET-PET and ways to overcome them by incorporating a translational component of profiling gene status in the methionine metabolic pathway. This translational correlative component to the MET-PET clinical trials can lead to a better understanding of the existing controversies and can enhance our knowledge for future randomization of GBM patients based on their tumor gene signatures to achieve better prognosis and treatment outcome. [ABSTRACT FROM AUTHOR]

Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet. Furthermore, MR also reduces mitochondrial oxidative stress in various organs such as liver, heart, kidneys, and brain. Other effects of MR have also been reported in such areas as cardiac function in response to hyperhomocysteinemia (HHcy), identification of molecular mechanisms in bone development, and enhanced epithelial tight junction. In addition, rodent models of cancer responded positively to MR, as has been reported in colon, prostate, and breast cancer studies. The beneficial effects of MR have also been documented in a number of invertebrate model organisms, including yeast, nematodes, and fruit flies. MR not only promotes extended longevity in these organisms, but in the case of yeast has also been shown to improve stress tolerance. In addition, expression analyses of yeast and Drosophila undergoing MR have identified multiple candidate mediators of the beneficial effects of MR in these models. In this review, we emphasize other in vivo effects of MR such as in cardiovascular function, bone development, epithelial tight junction, and cancer. We also discuss the effects of MR in invertebrates. [ABSTRACT FROM AUTHOR]

Background: L-Methionine (Met) is an essential amino acid for humans and is important for protein synthesis and the formation of polyamines and is involved in the synthesis of many metabolites, including homocysteine. Free-Met supplements have been claimed to have multiple positive effects; however, it remains unclear what the exact tolerance level is. With aging, Met metabolism changes, and increased plasma homocysteine is more apparent. High plasma concentrations of homocysteine are assumed to be associated with a high risk of developing atherosclerosis. Objective: We estimated the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) of supplemented, oral, free Met in healthy older adults by examining the increase in plasma homocysteine as the primary determinant. Design: We provided capsules with free Met to 15 healthy older adult subjects for 4 wk at climbing dosages of, on average, 9.2, 22.5, 46.3 and 91 mg · kg body weight-1 · d-1 with washout periods of 2 wk between each intake. Before, at 2 and 4 wk during, and 2 wk after each dosage, we studied a complete panel of biochemical blood variables to detect possible intolerance to increased Met intake. Plasma homocysteine and body composition were measured, and tolerance, quality of life, and cognitive function were assessed via questionnaires. Results: Plasma homocysteine was elevated with the highest dose of supplemented Met. The estimated NOAEL of supplemented Met was set at 46.3 mg · kg body weight-1 · d-1, and the estimated LOAEL of supplemented Met was set at 91 mg · kg body weight-1 · d-1 (on the basis of the actual intakes) in subjects independent of sex. No signs of intolerance were observed via questionnaires or other blood variables at the LOAEL. There were no meaningful changes in body composition. Conclusions: On the basis of plasma homocysteine, the NOAEL of supplemented Met intake is 46.3 and the LOAEL is 91 mg · kg body weight-1 · d-1 in healthy older adults. Both the NOAEL and LOAEL are not associated with meaningful effects on health and wellbeing. [ABSTRACT FROM AUTHOR]

Multiparous Holstein cows were assigned in a randomized complete block design into four treatments from 21 d before calving to 30 d in milk (DIM). Treatments were: MET [n = 19, fed the basal diet + rumen-protected methionine at a rate of 0.08% (w/w) of the dry matter, Smartamine ® M], CHO (n = 17, fed the basal diet + choline 60 g/d, Reashure ® ), MIX (n = 21, fed the basal diet + Smartamine ® M at a rate of 0.08% (w/w) of the dry matter and 60 g/d Reashure ® ), and CON (n = 20, no supplementation, fed the close-up and fresh cow diets). Follicular development was monitored via ultrasound every 2 d starting at 7 DIM until ovulation (n = 37) or aspiration (n = 40) of the first postpartum dominant follicle ( DF ). Follicular fluid from 40 cows was aspirated and cells were retrieved immediately by centrifugation. Gene expression of TLR4, TNF, IL1-β, IL8, IL6, LHCGR, STAR, 3β-HSD, P450scc, CYP19A1, IRS1, IGF, MAT1A, and SAHH, was measured in the follicular cells of the first DF. Cows in CON had higher TNF, TLR4, and IL1-β mRNA expression (11.70 ± 4.6, 21.29 ± 10.4, 6.28 ± 1.4, respectively) than CHO (2.77 ± 0.9, 2.16 ± 0.9, 2.29 ± 0.7, respectively), and MIX (2.23 ± 0.7, 1.46 ± 0.6, 2.92 ± 0.8, respectively). Cows in CON had higher IL1- β expression (6.27 ± 1.4) than cows in MET (3.28 ± 0.6). Expression of IL8 mRNA was lower for cows in CHO (0.98 ± 0.3) than cows in CON (4.90 ± 0.7), MET (6.10 ± 1.7), or MIX (5.05 ± 1.8). Treatments did not affect mRNA expression of LHCGR , STAR , P450scc , CYP19A , SAHH , MAT1A, or IL6 however, 3β-HSD expression was higher for cows in MET (1.46 ± 0.3) and MIX (1.25 ± 0.3) than CON (0.17 ± 0.04) and CHO (0.26 ± 0.1). Supplementation of methionine, choline, and both methionine and choline during the transition period did not affect days to first ovulation or number of cows that ovulated the first follicular wave. Plasma and follicular fluid estradiol and progesterone concentrations were not different among treatments. Methionine concentrations in the follicular fluid of the first postpartum DF was higher for cows in MET (18.2 ± 0.1 μ M ) than cows in CON (11.1 ± 0.9 μ M ). In conclusion, supplementing choline and methionine during the transition period changed mRNA expression in follicular cells and dietary methionine supplementation increased plasma and follicular fluid concentrations of methionine of the first postpartum DF in Holstein cows. [ABSTRACT FROM AUTHOR]

Methionine was demonstrated to be the most limiting amino acid for growing sheep when microbial protein is the predominant source of absorbable AA, but its specific requirement was not well quantified. The indicator amino acid oxidation (IAAO) method is based on the concept that when the most limiting amino acid (LAA) is deficient for protein synthesis, then all other AAs will be oxidized. With increasing intakes of the LAA, IAAO will decrease until the requirement for the LAA is met, and there is no further change in the indicator oxidation afterwards. Therefore, the catabolism of 13 C-Phe was used to indicate the effects of varying duodenal infusing levels of Met on the oxidation rate by 4-month-old Kazakh lambs (30.8 ± 0.4 kg BW). After a 6-d adaptation period, the IAAO test was conducted on d 7. Each lamb received a priming dose of 0.67 mg/kg BW of 13 C-Phe injected via the jugular vein, together with 0.18 mg/kg BW of NaH 13 CO 3 at time 0. Then, constant infusions [1.33 mg 13 C-Phe/(kg h) −1 ] were started. Breath samples were collected prior to and half-hourly between 90 and 210 min after the start of the 13 C-Phe infusions. An estimate of the mean Met requirement was determined by a breakpoint analysis of the rate of 13 CO 2 released by 13 C-Phe oxidation, with a 2-phase linear regression model. The oxidation rate of 13 C-Phe decreased (P < 0.001) with increasing amounts of methionine infused in a dose-dependent fashion up to 1.65 g/day, and it was not different from 1.65 to 2.15 g/day (P > 0.05). The mean Met requirement was estimated to be 1.28 ± 0.11 g/day of supplementation. The total postruminal minimum requirement of Met would be 2.02 g/day when the basal passage of Met (0.74 g/day) was summed. [ABSTRACT FROM AUTHOR]

Methionine (Met) is the first limiting amino acid in meat-type broiler chicken diets and serves as a lipotropic agent with antioxidant properties. The objectives of the current study is based on the hypothesis that Met supplementation will enhance n-3 fatty acid (FA) status, antioxidant content, lipid stability, and production indices in broilers fed flax. The effect of Met supplementation (50 and 100% above Cobb 500 requirement level) on tissue FA composition, tocopherol (Toc) content, lipid oxidation products, and growth performance of broilers fed flax is investigated. One hundred and twenty (n = 120) day-old Cobb chicks were fed corn-soybean meal-based diet containing 0% flax, (Control), 15% flax (Diet 1), Diet 1 + 50% more Met (Diet 2), and Diet 1 + 100% more Met (Diet 3) for 42 days. Total lipids in liver and adipose tissue was lowest in Diet 3 (P < 0.05). Feeding flax led to a reduction total lipids in breast muscle (P < 0.05) and was not affected by Met level (P > 0.05). α-Linolenic acid (18:3n-3) was highest in thigh muscle and liver of Diet 3 and adipose tissue of chickens fed Diet 2 and Diet 3 (P < 0.05). Total long chain (>20 C) n-3 FA was highest in the breast muscle of chickens fed Diet 2 and Diet 3 (P < 0.05). Total saturated FA were lowest in the breast and thigh muscle of Diet 3 fed birds (P < 0.05). Addition of Met led to an increase in α-Toc in breast muscle in birds fed Diet 2 and Diet 3 (P < 0.05). Lipid oxidation products were lower in the thigh muscle and adipose tissue of birds fed Diet 2 and Diet 3 than Diet 1 and Control (P < 0.05). Body weight gain was lowest in birds fed flax (P < 0.05). Met supplementation had no effect on weight gain or feed conversion in birds fed flax (P > 0.05). No effect of diet on feed consumption was observed (P > 0.05). Overall, results from the current study demonstrate that Met supplementation is a novel way to enrich tissues with n-3 FA and Toc in chickens fed flax. [ABSTRACT FROM AUTHOR]

This experiment was conducted to investigate the effects of dietary methionine (Met) on growth performance, carcass traits, meat quality and oxidative status of breast muscle in fast- (Arbor Acres, AA) and slow- (Partridge Shank, PS) growing broilers from 1 to 42 d of age. The broilers were divided into a 2 × 3 factorial design with 6 replicates per treatment. Diets were formulated to contain low (LM, 0.35 and 0.31% during 1 to 21 and 22 to 42 d), adequate (AM, 0.50 and 0.44%) and high (HM, 0.65 and 0.57%) Met, respectively. The main effects showed that the AA broilers had superior (P < 0.05) growth performance and carcass traits compared with those of the PS broilers. The breast muscle of the AA broilers had lower (P < 0.05) drip loss and malondialdehyde (MDA) content but higher (P < 0.05) cooking loss and glutathione peroxidase (GPX) activity than that of the PS broilers. Compared with the LM diets, the AM and HM diets increased (P < 0.05) 42-d BW, ADG, eviscerated yield and breast muscle yield only in the AA broilers. The AA broilers fed the HM diets had higher (P < 0.05) pH but lower (P < 0.05) L∗, cooking loss and ether extract content in breast muscle than those fed the LM diets. Compared with the LM diets, the HM diets resulted in strain-dependent changes (P < 0.05) in muscle oxidative status, with total antioxidant capacity (T-AOC) increased in the AA broilers, GPX activity increased and MDA content decreased in the PS broilers, and superoxide dismutase (SOD) activity increased in both strains of broilers. No differences were observed between the AM and HM diets except for T-AOC in breast muscle. In conclusion, the LM treatment negatively affected broiler growth performance, carcass traits, meat quality and oxidative status of breast muscle in a strain-dependent manner, particularly in the AA broilers, whereas the HM treatment had limited effects compared to the AM treatment. [ABSTRACT FROM AUTHOR]

Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor). NMRI nude mice were xenografted in the flank with U-87 MG-luc2 glioblastoma cells for tumor growth study following five intravenous (IV) injections of erymet with daily PN oral administration. Endpoints included efficacy and event-free survival (EFS). Finally, a repeated dose toxicity study of erymet combined with PN cofactor was conducted in CD1 mice. Recombinant MGL was cytotoxic on 4/6 cell lines tested. MGL half-life was increased from <24 h to 9-12 days when encapsulated in RBC. Conversion of PN into PLP by RBC was demonstrated. Combined erymet + PN treatment led to a sustained Met depletion in plasma for several days with a 85% reduction of tumor volume after 45 days following cells implantation, and a significant EFS prolongation for treated mice. Repeated injections in mice exhibited a very good tolerability with only minor impact on clinical state (piloerection, lean aspect) and a slight decrease in hemoglobin and triglyceride concentrations. This study demonstrated that encapsulation of methioninase inside erythrocyte greatly enhanced pharmacokinetics properties of the enzyme and is efficacy against tumor growth. The perspective on these results is the clinical evaluation of the erymet product in patients with Met starvation-sensitive tumors. [ABSTRACT FROM AUTHOR]

Methionine synthase (MTR) is one of the key enzymes of folate pathway, which play a key role in the construction, repair, and methylation of DNA. In this study, an association of MTR A2756G gene transition with prostate cancer in men populations of Kashan-Iran was investigated by a case-control study and an in silico analysis. The 200 samples including 100 patients with prostate cancer, as case group and 100 healthy men, as control group included in this study. MTR-A2756G genotyping was performed by PCRRFLP technique. Some in silico tools used to evaluate the effects of A2756G transition on the structure and function of MTR. Results showed that the AG genotype (OR: 2.4014, 95% CI: 1.3216-4.3636, P=0.0040), and GG genotype (OR: 3.6324, 95% CI: 1.2629-10.4475, P=0.0167) and G allele (OR: 2.0120, 95% CI: 1.3098-3.0905, P=0.0014) were associated with prostate cancer. In silico analysis showed that polymorphisms of the enzyme protein might change properties of MTR such as relative mutability and flexibility, which leads to alteration of stability and function of the enzyme. Based on the results, an MTRA2756G polymorphism which changes activity and stability of the methionine synthase associated with prostate cancer in men. It is a preliminary study and is presenting data for future comprehensive study for making a clinical conclusion that this gene transition is a biomarker for susceptibility to prostate cancer. [ABSTRACT FROM AUTHOR]

A total of 630 8-week-old female Hybrid Converter turkeys were divided (based on their body weights) into 6 groups, with 7 replicates per group and 15 birds per replicate. All birds were fed identical isocaloric and isonitrogenous wheat-soybean mealbased diets without (group 1) or with (groups 2 to 6) increasing levels of supplemental methionine (Met). The total content of Met in diets 1 to 6 was as follows (%): 0.29, 0.32, 0.40, 0.47, 0.56, and 0.61 at 9 to 12 wk of age and 0.24, 0.28, 0.34, 0.42, 0.47, and 0.55 at 13 to 16 wk of age. In both feeding phases, dietary Met levels in group 3 corresponded to those recommended by the National Research Council (NRC) (1994). Different dietary Met concentrations had no influence on feed intake, the final body weights of turkeys or carcass dressing percentage. Only in the first experimental feeding period (9 to 12 wk), the lowest dietary Met content significantly deteriorated the feed conversion ratio (FCR), whereas the highest Met content led to a significant improvement in FCR. After 8 wk of experimental feeding, dietary treatment 1 contributed to a significant increase in the activity of catalase (CAT) (blood and breast muscles) and superoxide dismutase (liver), an increase in lipid peroxides concentrations (blood, breast muscle) and a decrease in total glutathione (GSH+GSSG) content (breast muscles), in comparison to treatment 3 which is comparable to NRC recommendations. The highest level of dietary Met significantly increased blood total antioxidant potential (FRAP) values and glutathione content in the liver. To sum up, in the final feeding period between 9 and 16 wk of age, the growth performance of female turkeys was not deteriorated by dietary Met deficiency or excess (--30% and up to +50% relative to NRC recommendations, respectively). The total antioxidant potential can be effectively increased by dietary Met supplementation, but the highest Met level may lead to unbalanced oxidative changes in the body as indicated by lower FRAP values and a lower GSH/GSSG ratio in the liver. [ABSTRACT FROM AUTHOR]

Two experiments were conducted to evaluate the usefulness of urinary creatinine levels as a criterion for the estimation of protein and amino acid requirements in poultry. Here we studied the effects of dietary precursor levels of creatinine, methionine and arginine, on urinary creatinine excretion in experiments. Both experiments used 15 Chunky broilers chicks that were 8 days old. The chicks were assigned to three dietary groups, with five chicks each, and were fed an experimental diet for 7 days. The experimental diets mainly consisted of corn and soybean meal, and contained deficient, adequate, or excessive methionine and arginine levels in experiments 1 and 2, respectively. Excreta were collected for the last 3 days of the feeding trial, and chicks were terminated by dislocation of the neck at the end of the feeding trial to collect their livers. Creatinine concentration in the excreta and hepatic L-arginineglycine amidinotransferase (AGAT) activities were determined. Urinary creatinine levels increased with increasing both dietary methionine and arginine levels from deficient to adequate recommended by Japanese feeding standard (P<0.05), and then remained constant in experiments 1 and 2, respectively. The hepatic AGAT activity decreased when both dietary creatinine precursors levels were increased from deficient to adequate levels (p<0.05), and then remained constant. These results suggested that creatinine excretion was changed with both increasing dietary methionine and arginine, dose-dependently. [ABSTRACT FROM AUTHOR]

Aims Hyperhomocysteinemia (Hhcy) is an independent risk factor of atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms play an important role in the pathogenesis of atherosclerosis induced by Hhcy. However, the exact mechanism is still undefined. Lesional apoptotic cells and necrotic core formation contribute greatly to the progression of plaque. The present study sought to determine whether modification of histone methylation is involved in macrophage apoptosis and unstable plaque formation in the condition of Hhcy. Materials and methods The unstable plaque formation, lesional apoptotic cells and status of histone methylation were monitored in the aortas of Hhcy ApoE −/− mice induced by a high-methionine (HM) diet for 20 weeks. Involvement of histone methylation in macrophage apoptosis and foam cell formation were assessed in macrophage Raw 264.7 cells after being challenged with homocysteine alone or in combination with the histone methylation inhibitor BIX 01294. Key findings The unstable plaque formation and lesion apoptotic cells are increased in ApoE −/ − mice supplemented with high-methionine (HM), accompanied with a decreased expression of histone H3 lysine 9 dimethylation. Hhcy increases the apoptosis of macrophages and inhibits the histone H3 lysine 9 dimethylation, as well as the expression of histone methyltransferase G9a in vitro. Inhibition of histone methylation by BIX01294 enhances macrophage apoptosis and foam cell formation in vitro. Significance Our data suggest that Hhcy promotes the progression of atherosclerosis via macrophage apoptosis. Histone methylation might be involved in macrophage apoptosis and unstable plaque formation in methionine induced hyperhomocysteinemic ApoE −/− mice. [ABSTRACT FROM AUTHOR]

A growth trial was conducted to examine the effect of dietary digestible energy ( DE) content on methionine (Met) utilization and requirement in juvenile Nile tilapia ( Oreochromis niloticus). Ten iso-nitrogenous (288 g kg−1 protein) practical diets, with two DE levels (10.9 MJ kg−1; 12.4 MJ kg−1) and five methionine supplementation levels (0, 1, 2, 4 and 6 g kg−1), were hand-fed twice daily to triplicate groups of Nile tilapia (initial body weight 8.95 ± 0.06 g) for 8 weeks. Weight gain ( WG) and specific growth rate ( SGR) increased significantly with increasing dietary methionine concentration at the same DE content ( P < 0.001). At the same dietary methionine level, WG and SGR of fish fed high- DE diets were significantly higher than that of fish fed low- DE diets ( P = 0.0001), although no interaction was found between dietary DE and methionine supplementation. Based on quadratic regression analysis between dietary methionine concentration and weight gain, optimal methionine requirement for maximum growth, expressed as g Met required kg−1 diet (low- versus high- DE diets), increased as diet DE concentration increased (7.34 versus 9.90 g kg−1 diet, respectively; with cysteine 4.70 g kg−1 diet). The results indicated that diet DE content affects methionine utilization and requirement in juvenile Nile tilapia, fish fed high- DE diets required more methionine for maximum growth. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD. [ABSTRACT FROM AUTHOR]

Despite clear beneficial effects, studies on the efficacy of different formulations of micronutrients and vitamins in the treatment of male infertility are still very limited. The aim of the study was to compare the efficacy of methionine and novel formulation Metovitan based on the combination of methionine, thiamine, nicotinamide, α-tocopherol acetate and zinc salt as remedies for prevention of anti-tuberculosis drugs (ATD) anti-fertility effects in male rats. ATD co-administration resulted in testicular CYP2E1, CYP2C23 and CYP3A2 transcriptional activation. Methionine and Metovitan regulated the level of CYP2E1 and CYP3A2 mRNA expression. Methionine unaffected CYP2C23 mRNA level, while Metovitan effectively normalized this parameter. The use of methionine did not allow normalizing of DNA fragmentation processes in testes, while Metovitan provided decrease in the number of DNA fragments to the control level. Both substances significantly decreased p-nitrophenol hydroxylase activity and prevented pro/antioxidant parameters imbalance in testes of ATD-treated rats. The end results of methionine and Metovitan application were partial or complete restoration of altered spermatogenesis parameters with subsequent increase in sperm count and fertility. Ameliorating effects may be attributed to antioxidant properties and modulating effects on testicular CYPs. More pronounced beneficial Metovitan effects might be due to synergic effects of its components. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects. To test this hypothesis, C57BL/6 mice were fed a methionine-choline-deficient (MCD) diet for 8 weeks. After four weeks into MCD feeding, mice were provided with plain water (control) or water containing 2 mg/mL of GABA for the subsequent 4 weeks. Using this MCD diet-induced NASH model, we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice. This increased liver damage was confirmed by higher levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) compared to the control group. In accordance with increased liver steatohepatitis, NASH-related and inflammatory gene expression (collagen α1, tissue inhibitor of metalloproteinase-1, TNF-α) in the liver was markedly increased in GABA-treated mice. Furthermore, GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB-73 hepatocyte death. Such effects were abolished when GABAwas treated with bicuculline, a competitive antagonist of GABA receptors. These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression. [ABSTRACT FROM AUTHOR]

Melanoma is an aggressive cancer, the incidence of which is increasing worldwide. Limited therapies are currently available, particularly following metastasis. The aim of the present study was to investigate the inhibiting effect of methionine enkephalin (MENK) on human melanoma via opioid receptors. The results of the present study revealed that MENK markedly regulates the proliferation of A375 cells, causing cell cycle arrest in G0/G1 phase and a decrease in the percentage of cells in S and G2/M phases. Reverse transcription-quantitative polymerase chain reaction demonstrated that MENK treatment increased opioid receptor expression in A375 cells. Furthermore, the expression level of survivin, an inhibitory apoptotic protein, was 1.1% of the level in the control group in the MENK group following 48 h of treatment. In conclusion, the results of the present study revealed, to the best of our knowledge for the first time, that MENK may inhibit growth and induce apoptosis of A375 cells, and describes a potential mechanism underlying these effects. Therefore, MENK should be investigated as a primary therapy for human melanoma cancer and as an adjuvant to other chemotherapies. Further studies are required to develop an optimal strategy for the use of MENK for the treatment of human cancers. [ABSTRACT FROM AUTHOR]

Lysine (Lys) and Methionine (Met) as two primary essential amino acids and precursors of carnitine biosynthesis are involved in most of economical traits function in domestic animals. We assessed the impact of dietary Lys and Met on the performance, lipid redistribution, intramuscular fat, carcass quality and especially phenotypic correlations among some studied parameters in broiler chickens. 300 day-old male Ross 308 chicks were randomly divided among 5 treatments, with 4 replicates per treatment. There were 15 chicks in each replicate in a completely randomized design. Same basal diet was supplemented with 5 levels of synthetic Lys and Met in amount of 0, 10, 20, 30 or 40% higher than National Research Council (NRC), 1994 recommendation for starter and grower periods. The collected data were analyzed and determined the correlation coefficient by SAS software and Duncan's test was used to compare the means on a value of (P<0.05). The results indicated that the two highest levels of Lys and Met treatments (30 and 40% more than NRC recommendation) led to significant increase in carcass efficiency, European Production Efficiency Factor (EPEF), blood albumin, breast muscle, heart, spleen, lymphocytes and liver weight (P<0.05), whereas feed conversion ratio (FCR), crude fat contents of breast and thigh muscles and plasma triglyceride were the least in these two treatment groups (P<0.05). Statistical analysis also showed many numbers of significant (at levels of P<0.01 or P<0.05) positive or negative correlations between the studied traits. For example highly positive correlations between carcass efficiency with heart, liver, spleen and breast weights and negative correlations with FCR, abdominal fat, plasma triglyceride, heterophyles breast and thigh fat was observed. As a conclusion of present study, dietary Lys and Met in higher levels of NRC recommendation could influence the parameters relate to performance, fat distribution, carcass quality and immune system in broilers. [ABSTRACT FROM AUTHOR]

A 2×5 factorial experiment, using 2 dietary methionine levels (0.28% and 0.48%) and 5 dietary choline levels (0, 394, 823, 1,239, and 1,743 mg/kg), was conducted to study the effects of dietary methionine status on choline requirements of starter white Pekin ducks from 7 to 28 days of age. Four hundred eighty 7-d-old male White Pekin ducks were randomly allotted to ten dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 28 d of age, weight gain, feed intake, and feed/gain were measured and the legs of all ducks from each pen were examined for incidence of perosis. Perosis and growth depression were observed in choline-deficient ducks and supplementation of choline reduced perosis and significantly increased weight gain and feed intake regardless of dietary methionine levels (p<0.05). In addition, significant positive effects of dietary methionine supplementation on weight gain, feed intake, and feed/gain were observed at any choline level (p<0.05). Supplementation of 1,743 mg/kg choline in diets alleviated the depression of weight gain and feed intake caused by methionine deficiency at 0.28% methionine level. The interaction between choline and methionine influenced weight gain and feed intake of ducks (p<0.05). At 0.28% methionine level, 1,743 mg/kg choline group caused 4.92% and 3.23% amount of improvement in weight gain and feed intake compared with 1,239 mg/kg choline group, respectively. According to the broken-line regression, the choline requirements of starter Pekin ducks for weight gain and feed intake were 1,472 and 1,424 mg/kg at 0.28% methionine level and 946 and 907 mg/kg at 0.48% methionine level, respectively. It suggested the choline recommendations of starter Pekin ducks on a semi-purified diet were 1448 mg/kg at 0.28% methionine level and 927 mg/kg at 0.48% methionine level, respectively. Compared with the adequate methionine level, menthionine deficiency markedly increased the choline requirements of ducks. [ABSTRACT FROM AUTHOR]

Background: Folate and methionine metabolism enzymes could affect DNA synthesis and repair, and their methylation and polymorphisms have been associated with some forms of cancer. This study was carried out to investigate whether theMTHFRC677T (rs1801133),MTHFRA1298C (rs1801131) andTYMS2R/3R (rs34743033) polymorphisms are associated with susceptibility to retinoblastoma in an Iranian population. Methods: A case-control study was conducted involving 96 patients with retinoblastoma and 204 healthy controls. Genotyping of theMTHFRC677T,MTHFRA1298C, andTYMS2R/3R polymorphism were assessed by PCR-RFLP, high resolution melting curve (HRM), and PCR methods, respectively. Results: The frequencies ofMTHFR677CT and 677TT genotypes were significantly lower in cases than controls (pvalues, 0.012 and 0.034, respectively). TheMTHFR677T allele was significantly lower in patients than in the control group (p= 0.003). In contrast, no association was observed with respect to theMTHFRA1298C andTYMS2R/3R polymorphisms. Conclusions: TheMTHFRC677T polymorphism was associated with the risk of retinoblastoma in this Iranian population and the T allele had a protective effect on the susceptibility to retinoblastoma. [ABSTRACT FROM AUTHOR]

A feeding experiment was conducted to determine dietary methionine requirement of bullfrog Rana (Lithobates) catesbeiana . Bullfrogs were fed six experimental diets containing 0.63%, 1.00%, 1.42%, 1.78%, 2.26% or 2.68% methionine for 8 weeks. After the feeding experiments, growth performance, body composition, blood biochemistry and expression levels of hepatic genes were determined. The results showed that growth and feed utilization were significantly affected ( P < 0.05) by dietary methionine levels. Weight gain (WG) and protein efficiency ratio (PER) both increased with increasing level of dietary methionine from 0.63% to 1.42% and then decreased. While, the variation trend of feed conversion ratio (FCR) is just opposite with WG and PER. Crude lipid concentrations of whole body and muscle tissue were also significantly affected ( P < 0.05) by dietary methionine levels. However, there was no significant difference ( P > 0.05) in amino acid composition in muscle among methionine treatments. Triglyceride (TG) and cholesterol (CHO) levels, as well as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, were all significantly affected ( P < 0.05) by dietary methionine levels. TG and CHO levels decreased as dietary methionine increased from 0.63% to 1.78% and then increased with further increases in methionine. Serum AST and ALT activities in bullfrogs fed with 0.63% methionine diet were both significantly higher ( P < 0.05) than in bullfrogs fed other diets. Gene expressions in bullfrogs fed with 1.00%, 1.42% and 1.78% methionine diets was higher ( P < 0.05) than these of other groups. On the basis of WG and PER, the optimal level of dietary methionine for bullfrogs was estimated to be between 1.53% and 1.62% of diet using second-order polynomial regression analysis. The corresponding optimal level of total sulfur amino acids in the diet of bullfrogs is therefore between 1.79% and 1.88% of diet in the presence of 0.26% cystine. Statement of relevance The authors have declared that no competing interests exist. [ABSTRACT FROM AUTHOR]

Hypermethioninemia is a condition defined as elevated plasma methionine levels and may be a consequence of different conditions that include non-genetic and genetic causes. In severe cases, hypermethioninemia may lead to development of neurological and hepatic impairments, but mechanisms are still not well elucidated. Therefore, this review aims to reunite the knowledge acquired about the methionine-induced brain and liver toxicity focusing on the results obtained by studies from patients, in vitro experiments, and in vivo animal models. In general, some studies have shown that methionine decreases Na,K-ATPase activity, induces oxidative stress, increases acetylcholinesterase activity, and leads to dendritic spine downregulation in brain. Concerning to liver, hypermethioninemia seems to provoke changes in cell morphology, lipid accumulation, oxidative stress, inflammation, and ATP depletion. It is possible to infer that oxidative damage is one of the most important mechanisms responsible for methionine toxicity, since different studies showed that this amino acid induces oxidative stress in brain and liver tissues. Besides, reactive oxygen species may mediate other alterations induced by methionine, such as the reduction in brain Na,K-ATPase activity, and liver inflammation. [ABSTRACT FROM AUTHOR]

Using an immunohistochemical technique, we mapped the immunoreactive structures containing methionine-enkephalin-Arg 6 -Gly 7 -Leu 8 (Met-8) (a marker for the pro-enkephalin system) in the human diencephalon. Compared with previous studies, we observed a more widespread distribution of Met-8 in the human diencephalon. Met-8-immunoreactive cell bodies and fibers exhibited a more widespread distribution in the hypothalamus than in the thalamus. We observed six populations of Met-8-immunoreactive cell bodies. These perikarya were observed in the paratenial thalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, lateral hypothalamic area, pallidohypothalamic nucleus and in the paraventricular hypothalamic nucleus (posterior part). In the thalamus, Met-8-immunoreactive fibers were primarily observed in the midline region, whereas in the hypothalamus, these fibers were widely distributed. In general, a moderate/low density of Met-8-immunoreactive fibers was observed in the diencephalic nuclei. A moderate density was observed in the paraventricular thalamic nucleus, reuniens thalamic nucleus, lateral and medial geniculate nuclei, dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus (posterior part) and ventromedial hypothalamic nucleus. The present study is the first to demonstrate the presence of clusters of Met-8-immunoreactive cell bodies in the human thalamus and hypothalamus, the distribution of fibers containing neuropeptides in the hypothalamus and the presence of these fibers in several thalamic nuclei. This neuroanatomical study will serve to elucidate the physiological roles of Met-8 in future studies of the human diencephalon. [ABSTRACT FROM AUTHOR]