High Levels Of Methionine Research Articles

Nutritional Management of Neonatal and Infant Liver Disease

After completing this article, readers should be able to: 1. Describe the caloric requirements of a neonate who has chronic liver disease. 2. Identify the vitamin and mineral deficiencies associated with cholestasis and the methods used to correct these deficits. 3. Describe the relationship between total parenteral nutrition and the development of chronic liver disease. 4. Delineate the relationship between malnutrition at the time of liver transplantation and subsequent morbidity and mortality. 5. List the best measurements of nutrition assessment in infants who have chronic liver disease. The liver is involved in many of the body’s metabolic processes, including: regulation of protein, fat, and carbohydrate metabolism; vitamin storage and activation; and detoxification and excretion of waste products. The healthy liver synthesizes and excretes bile salts. With cholestatic liver diseases, poor bile flow results in fat malabsorption because micelles, which solubilize long-chain fatty acids, cannot form without bile salts. Fat malabsorption results in enteric losses of the fat-soluble vitamins A, D, E, and K. Impaired liver function can lead to nutrient deficiencies and eventually protein-energy malnutrition. All of these factors, combined with the common symptoms of anorexia and poor dietary intake, make malnutrition common in chronic liver disease, particularly if it occurs in infants, who are more vulnerable to the debilitating effects of malnutrition because of their higher energy and growth requirements. A wide range of deficits occurs in most chronic liver diseases of children (Table 1⇓ ). Malnutrition itself may induce further derangements of liver function because the liver requires energy for a number of synthetic, storage, and detoxification functions. View this table: Table 1. Nutritional Risk Factors in Acute and Chronic Liver Disease The need for aggressive, early nutrition support in neonates has been well established and discussed extensively. Some centers routinely use a “standardized” approach to nutrition support; we use a “tailored” approach that entails parenteral or …

The history of folic acid.

The history of folic acid.

Aspartate kinase 2. A candidate gene of a quantitative trait locus influencing free amino acid content in maize endosperm.

The maize (Zea mays) Oh545o2 inbred accumulates an exceptionally high level of free amino acids, especially lysine (Lys), threonine (Thr), methionine, and iso-leucine. In a cross between Oh545o2 and Oh51Ao2, we identified several quantitative trait loci linked with this phenotype. One of these is on the long arm of chromosome 2 and is linked with loci encoding aspartate (Asp) kinase 2 and Asp kinase (AK)-homoserine dehydrogenase (HSDH) 2. To investigate whether these enzymes can contribute to the high levels of Asp family amino acids, we measured their specific activity and feedback inhibition properties, as well as activities of several other key enzymes involved in Lys metabolism. We did not find a significant difference in total activity of dihydrodipicolinate synthase, HSDH, and Lys ketoglutarate reductase between these inbreds, and the feedback inhibition properties of HSDH and dihyrodipicolinate synthase by Lys and/or Thr were similar. The most significant difference we found between Oh545o2 and Oh51Ao2 is feedback inhibition of AK by Lys but not Thr. AK activity in Oh545o2 is less sensitive to Lys inhibition than that in Oh51Ao2, with a Lys I50 twice that of Oh51Ao2. AK activity in Oh545o2 endosperm is also higher than in Oh51Ao2 at 15 d after pollination, but not 20 d after pollination. The results indicate that the Lys-sensitive Asp kinase 2, rather than the Thr-sensitive AK-HSDH2, is the best candidate gene for the quantitative trait locus affecting free amino acid content in Oh545o2.

SCFMet30-mediated control of the transcriptional activator Met4 is required for the G1-S transition

Progression through the cell cycle requires the coordination of basal metabolism with the cell cycle and growth machinery. Repression of the sulfur gene network is mediated by the ubiquitin ligase SCF(Met30), which targets the transcription factor Met4p for degradation. Met30p is an essential protein in yeast. We have found that a met4Deltamet30Delta double mutant is viable, suggesting that the essential function of Met30p is to control Met4p. In support of this hypothesis, a Met4p mutant unable to activate transcription does not cause inviability in a met30Delta strain. Also, overexpression of an unregulated Met4p mutant is lethal in wild-type cells. Under non-permissive conditions, conditional met30Delta strains arrest as large, unbudded cells with 1N DNA content, at or shortly after the pheromone arrest point. met30Delta conditional mutants fail to accumulate CLN1 and CLN2, but not CLN3 mRNAs, even when CLN1 and CLN2 are expressed from strong heterologous promoters. One or more genes under the regulation of Met4p may delay the progression from G(1) into S phase through specific regulation of critical G(1) phase mRNAs.

Influence of abomasal infusion of high levels of lysine or methionine, or both, on ruminal fermentation, eating behavior, and performance of lactating dairy cows.

Four multiparous late-lactation Holstein cows were fed a basal ration designed to be co-limiting in intestinally absorbable supplies of methionine and lysine. Cows were supplemented with no amino acids, lysine by abomasal infusion to 140% of the calculated intestinally absorbable requirement, methionine by abomasal infusion to 140% of requirement, or both amino acids in a 4 x 4 Latin square design with 28-d periods. Unsupplemented cows consumed 23.8 kg/d of dry matter and produced 36.9 kg/d of milk containing 3.70% fat, 3.22% protein, and 4.82% lactose. Cows ate less dry matter and produced less milk and milk lactose, and tended (P = .06 or .08) to produce less milk protein when abomasally infused with methionine alone or together with lysine. Infusion of lysine alone resulted in production values numerically between those of unsupplemented cows and those cows supplemented with methionine alone or together with lysine. Evaluation of the results with two metabolic models of dairy cows indicated that performance of unsupplemented cows may have been limited by delivery of metabolizable or digestible protein, or intestinally absorbable lysine, isoleucine, or histidine, depending on the metabolic model used to evaluate animal performance. Regardless, results are consistent with those using nonruminant species, which have shown that imbalanced profiles of intestinally absorbable amino acids are associated with reduced dry matter intake and animal performance. Results also show that negative effects on performance of lactating dairy cows can occur if methionine is supplied at levels substantially in excess of calculated intestinally absorbable requirements, either alone or together with lysine.

The Effect on the Lipid Metabolism of Tsaiya Ducks When High Levels of Choline or Methionine are Added to the Duck's Diet

The Effect on the Lipid Metabolism of Tsaiya Ducks When High Levels of Choline or Methionine are Added to the Duck's Diet

Évolution favorable sous traitement par NTBC de l'insuffisance hépatique aiguë révélatrice de la tyrosinémie héréditaire de type I

Hereditary tyrosinemia type I is a disease with a severe prognosis. Main causes of death are acute liver failure, neurologic crises and hepatocarcinoma. NTBC, which acts as an inhibitor of the 4-hydroxyphenylpyruvate dioxygenase, prevents the formation of toxic metabolites involved in hepatic, renal and neurologic lesions. Results of NTBC therapy used in three infants with type I tyrosinemia who presented with acute liver failure are reported. The diagnosis relied on the finding of high plasmatic levels of tyrosine and methionine, and abnormal urinary excretion of succinyl acetone and delta aminolevulinic acid. Treatment with NTBC was initiated within 2 to 8 days from onset of symptoms. Signs of liver failure resolved after 3 weeks therapy. After 12 to 39 months of follow-up, outcome remains favorable. The results reported here highlight the efficiency of NTBC in type I tyrosinemia with early acute onset. However, the long term outcome needs to be determined with regards to prevention of hepatocarcinoma and toxicity of the drug.

The effects of feeding compound concentrate supplements with either a low or high level of true methionine digested in the small intestine (DVmet) to dairy cows

The Dutch DVE/OEB protein evaluation system (Tamminga et al., 1994) gives predictions for the concentration of whole true protein digested in the small intestine (DVE) in cattle feeds, but not for the concentration of single amino acids. Therefore, new standard methods has been introduced for the prediction of true methionine and lysine digested in the small intestine (DVmet and DVlys, respectively) in cattle feeds based on the principles of the calculation of DVE (van Duinkerken and Blok, 1998). These methods give the opportunity to select particular feeds and concentrate ingredients in order to manipulate the concentration of DVmet and DVlys in diets and compound concentrates. However, in the Netherlands, there are no recommendations for DVmet and DVlys in dairy cow rations established yet. An experiment was therefore conducted to study the effects of feeding compound concentrate supplements with either a low (L) or high (H) level of DVmet on feed intake and milk production in dairy cows fed a grass and maize silage mixture ad libitum

Effects of different levels of methionine and ruminally undegradable protein on the amino acid profile of effluent from continuous culture fermenters.

Eight dual-flow continuous culture fermenters were used to study the effects of feeding different levels of methionine and ruminally undegradable protein (RUP) on the amino acid (AA) profile of protein residue after microbial fermentation. Four isocaloric (1.76 Mcal/kg of NE(l)) and isonitrogenous (17.7% CP) diets were formulated based on NRC recommendations for a 630-kg cow producing 42 kg/d of milk. Two dietary treatments, diets HmLr (high methionine, low RUP) and HmHr (high methionine, high RUP), were formulated to meet, but not exceed, more than 140% of each estimated individual AA requirement for milk production. Diets LmLr (low methionine, low RUP) and LmHr (low methionine, high RUP) were formulated to meet the estimated individual AA requirement except for methionine. Diets HmLr and LmLr contained 35% RUP, and diets HmHr and LmHr contained 43% RUP. Digestion of DM, OM, and NDF was not affected (P>.05) by treatments. Tyrosine, cystine, and threonine ranked as the most resistant AA to microbial fermentation, whereas methionine and lysine ranked among the most degradable. In general, microbial degradation of individual AA followed the same pattern as CP degradation, being higher in diets HmLr and LmLr and lower in diets HmHr and LmHr. Because true microbial digestion of methionine, cystine, tyrosine, and isoleucine was reduced in the presence of high levels of methionine, we concluded that supplementation of dietary methionine could increase flows of these amino acids to the duodenum.

Saudi Experience with Classic Homocystinuria

Classic homocystinuria is an autosomal recessive disorder due to cystathionine ss-synthase deficiency. The clinical, radiological and neurophysiological findings of classic homocystinuria diagnosed at King Faisal Specialist Hospital and Research Centre (KFSH&RC) are presented in this report. Twenty-four patients (15 females and 9 males) were referred to KFSH&RC for work-up of mental retardation, seizures, thrombo-embolic episodes and dislocation of the ocular lenses. The common clinical findings included ectopia lentis (20 patients), skeletal system involvement (18 patients), vascular system involvement (9 patients), and mental retardation (all patients to varying degrees). Unusual findings consisted of a patient who developed severe lower gastrointestinal bleeding, a patient with insulin-dependent diabetes mellitus, probably due to vasculopathy, and another having severe bronchiectasis, which may have been due to fibrillin disruption, and required the resection of a lobe of the lung. The parents of 21 patients were first-degree relatives, and 19 patients had one or more family members affected by the same disease. All patients had markedly elevated plasma levels of methionine. Cystathionine synthase activity in the fibroblast was measured in 25% of the patients and was deficient. Only four patients responded to pyridoxine and their methionine level decreased to almost normal range. The aim of this study was to increase the awareness of this disease in the scientific and medical community, in particular in the general pediatrician working in Saudi Arabia who first encounters the clinical manifestations of the disease. Early detection through tandem mass spectrometry of blood spot screening and treatment are important, and may prevent the major complications of this disease.

Effect of Isoleucine on Toxin Production by Clostridium difficile in a Defined Medium

Supplementation of a carbohydrate-free minimal medium with a high level (100 mM) of histidine, methionine, valine, isoleucine, proline and leucine, in particular isoleucine, markedly increased toxin production by Clostridium difficile VPI 10463. The effect of isoleucine was further examined. Increasing the concentration of isoleucine from 20 to 100 mM remarkably increased toxin production, while bacterial growth decreased gradually. Amino acid analysis of the culture revealed that, at 100 mM isoleucine, consumption of isoleucine was remarkably increased. During the incubation period when toxin titers increased markedly but bacterial growth was declining, isoleucine, leucine and cysteine were taken up preferentially and alanine and cystathionine, which were not found at 1 mM isoleucine, were produced in large quantities. These findings suggest that isoleucine may play an important role in toxin production by C. difficile and that alanine and cystathionine production may be co-regulated with the toxin production in the absence of fermentable carbohydrates.

High levels of dietary protein or methionine have different effects on cysteine metabolism in rat hepatocytes.

This study clearly indicates that relatively high levels of both CDO and CSAD activity are needed for substantial taurine synthesis and that protein and methionine supplementation, at equimolar sulfur amino acid levels, are not equivalent in terms of their effects on cysteine catabolic enzyme activities and cysteine metabolism in hepatocytes. Evidence for a reciprocal regulation of cysteine catabolism (or CDO activity) and GSH synthesis (or gamma-glutamylcysteine synthetase activity) in rat liver was also obtained. Although very high levels of protein and methionine were fed in this study, previous studies with lower levels of protein or methionine showed similar changes in cysteine metabolism. Several questions regarding regulation of cysteine metabolism remain unanswered. Beyond sulfur amino acid availability, animals fed high protein diets appear to have other signals for regulation of CDO and CSAD activities. These signals may be related to the different hormonal and metabolic state of these animals. Furthermore, little is known about the molecular mechanisms involved in the observed changes in CDO and CSAD activities. The association between CDO activity and CDO protein has not been evaluated. Jerkins and Steele, using immunochemical detection and quantification of CSAD protein in rat liver, showed that changes in CSAD protein concentration were correlated to changes in CSAD activity. The exact mechanisms or direct effectors which bring about changes in CDO and CSAD activities have yet to be determined. Further exploration of these potential regulatory mechanisms needs to be conducted to better understand the response of cysteine sulfinate-dependent cysteine catabolism to high levels of dietary protein or sulfur amino acids.

Methionine inhibits developmental aggregation of Myxococcus xanthus by blocking the biosynthesis of S-adenosyl methionine

Previous studies showed that high concentrations of methionine (> 1 mM) inhibited aggregation and fruiting body formation in Myxococcus xanthus (E. Rosenberg, D. Filer, D. Zafriti, and S. H. Kindler, J. Bacteriol. 115: 29-34, 1973, and J. M. Campos and D. R. Zusman, Proc. Natl. Acad. Sci. USA 72:518-522, 1975). However, the mechanism for the inhibition was unclear. In this study, we found that high levels of methionine inhibited the biosynthesis of S-adenosylmethionine (SAM) and that reduced intracellular levels of SAM are correlated with defective chemotactic movements and reduced developmental gene expression. In addition, we found that methionine analogs and high concentrations of amino acids which are known to affect SAM synthesis in other bacteria, such as threonine, lysine, and isoleucine, also caused reduced cellular levels of SAM and blocked fruiting body formation in M. xanthus. These results indicate that SAM is required for development of M. xanthus and the inhibitory effect of methionine on development results, at least in part, from its blocking of the biosynthesis of SAM.

The influence of methionine and its metabolites on the progression of atherosclerosis in rabbits

The effects of a high level of methionine on the changes of lipid and amino acid metabolism were investigated. Eighteen New Zealand White rabbits were divided into three groups; a methionine group, which was fed a diet supplemented with 3% D, L-methionine, a Cholesterol+Methionine group, which was fed a 3% D, L-methionine and a 0.2% cholesterol diet, and a Cholesterol group which was fed a 0.2% cholesterol diet for 22 weeks. The plasma triglyceride, cholesterol, homocysteine, cysteine and serum SO4(2-) levels were measured and compared. On the first and the final day of the experiment, lipid peroxide levels in blood samples were also measured. We found that the Methionine group and the Cholesterol+Methionine group showed elevated levels of plasma triglyceride, cholesterol, homocysteine, cysteine, serum SO4(2-) and lipid peroxide compared with the Cholesterol group. More prominent fat deposits in the aorta were observed in the Methionine group and the Cholesterol+Methionine group than in the Cholesterol group. Our results indicated that the interaction of cholesterol with methionine or its derivatives plays a role in the progression of atherosclerosis.

Hypercholesterolemic Responses in Rabbits to Selected Groups of Dietary Essential Amino Acids

AbstractIn rabbits, elevation of LDL cholesterol is produced by feeding a cholesterol-free, semipurified diet containing 30% casein amino acid mixture, but not by feeding the same diet containing 14.7% of the casein amino acid mixture, corresponding to a normal level of dietary protein. The hypercholesterolemic response was greater when all essential amino acids except arginine or all ketogenic essential amino acids (lysine, leucine, isoleucine, threonine, phenylalanine, tryptophan and glycine) were selectively fed at three times the normal level. In the present experiments, the same high levels of lysine, leucine and methionine produced a substantial hypercholesterolemia, addition of either isoleucine + threonine or isoleucine + valine did not enhance the effect, and a mixture of threonine, histidine, phenylalanine, tryptophan and glycine gave only a moderate response. A combination of lysine and methionine produced a greater effect than either lysine and leucine or leucine and methionine. Hypercholesterolemic diets containing high levels of lysine and leucine did not cause significantly greater plasma ketone bodies or free fatty acids. Differences in growth rates and ketogenic responses were not generally correlated with hypercholesterolemia.

Effect of methionine and nitrous oxide on homocysteine export and remethylation in fibroblasts from cystathionine synthase-deficient, cb1G, and cb1E patients.

We investigated the nitrous oxide-induced inactivation of methionine synthase and the concurrent homocysteine (Hcy) export in mutant fibroblasts with defects in the homocysteine catabolizing enzyme, cystathionine beta-synthase, or in methionine synthase, which carries out homocysteine remethylation. The fibroblasts were incubated in various concentrations of methionine to create conditions favoring methionine conservation or catabolism. In cystathionine beta-synthase-deficient cells, high medium methionine partly protected the enzyme against inactivation, as previously found in normal fibroblasts. The Hcy export rate at low methionine levels was low (0.2-0.6 nmol/h/10(6) cells), and increased 2-3-fold at high methionine levels. Nitrous oxide enhanced Hcy export rate at low methionine, so that in the presence of nitrous oxide, the Hcy export became less dependent of methionine. In cb1G cells, the enzyme inactivation was moderate and independent of medium methionine. The Hcy export rate was intermediate (0.5-0.8 nmol/h/10(6) cells) at low methionine levels, and increased moderately (< 2-fold) at high methionine levels or following nitrous oxide exposure. In cb1E mutants, the enzyme activity was not affected by nitrous oxide, and the Hcy export was high (0.8-1.6 nmol/h/10(6) cells) and independent of methionine and nitrous oxide. These data suggest that Hcy remethylation and cystathionine beta-synthase activity are major determinants of Hcy export at low and high methionine, respectively. The low susceptibility of methionine synthase to nitrous oxide in the presence of high methionine or in cb1G or cb1E mutants is probably related to low catalytic turnover.

Maternal effect on high methionine levels in hybrid corn

The inbred BSSS53 containing the Zpr10/(22) factor on chromosome 4 that influences the levels of the high-methionine 10 kD zein protein in maize encoded by the Zps10/(22) locus on chromosome 9 was crossed reciprocally with a normal maize line. The amino acid composition of the prolamine fraction from progeny seeds of both reciprocal crosses and selfed parents was determined. The level of protein-bound methionine in the two hybrids shows a maternal influence rather than a simple dosage effect as one would expect for a semidominant gene. The large margin of difference in protein-bound methionine between the two reciprocal hybrids provided an opportunity to test its nutritional significance by a feeding trial of 1 d old male Peterson's Arbor Acre chicks. Although the efficiency of weight gain per g of food consumed is the same in both groups, the high methionine corn meal improved growth performance between 35 and 54%.

Interaction of dietary calcium, manganese, and manganese source (Mn oxide or Mn methionine complex) on chick performance and manganese utilization

Two trials were conducted to determine the utilization of manganese (Mn) as influenced by the level and source of Mn and the level of dietary calcium (Ca) in broiler chickens. Trial One was a 2 x 2 x 3 factorial arrangement of two Mn sources (Mn methionine or manganous oxide), two levels of dietary Ca (1.8 or 1.0), and three levels of supplemental Mn (30, 60, or 200 mg/kg) fed until 4 wk of age. Total phosphorus (available phosphorus) levels were 0.70% (0.48%) during all ages. High levels of dietary Ca caused a slower early rate of growth (0.53 vs. 0.64 kg) for chicks fed 1.8 vs 1.0% Ca, respectively. Chick weight was equivalent for all diets within the Ca-treatment group, except the dietary combination of high Ca and 200 mg/kg Mn as Mn methionine. Bone and liver Mn were significantly increased as the Mn level increased, but were not affected by the Mn source. Chicks fed 1.8% Ca had higher levels of bone Mn (9.28 ppm) than chicks fed 1.0% Ca (7.23 ppm). High levels of dietary Ca and 200 ppm Mn methionine dramatically depressed early growth, feed intake, and bone ash in this trial, raising the question of a diet x environment (heat-stress) effect. Trial Two was a 2 x 2 factorial arrangement of two levels of dietary Ca (1.8 or 1.0%) and two Mn sources (200 mg/kg Mn as Mn methionine or MnO) up to 3 wk of age in a controlled heat-stress environment. No growth depression in the chicks fed high levels of Ca and Mn methionine was observed. In the presence of high levels of dietary Ca, bone Mn was significantly higher when chicks were fed the MnO source. In summary, dietary Ca did not decrease Mn utilization in these trials, and availability of Mn in Mn methionine as a source compared to MnO depended on dietary Ca levels.

A novel proline-rich protein from wheat

A cDNA (WPRP1) encoding a wheat proline-rich protein has been isolated and sequenced. The amino acid composition shows 45% proline, with high levels of methionine, lysine and glutamic acid. The derived 378 residue amino acid sequence has a highly repetitive structure which is unlike those of other proline-rich proteins. The WPRP1 cDNA clone was used to determine the copy number and chromosomal location of the WPRP1 gene by restriction fragment length polymorphism analysis of wheat inbred lines. Although WPRP1 is encoded by a single-copy gene it is also a representative of a larger family of related sequences. RNA gel blot analysis showed that expression of WPRP1 is highest in rapidly growing tissue which together with its amino acid composition suggests a structural role for the encoded protein.

Influence of diet composition on weight gain and skeletal development of White Leghorn chicks reared to four weeks of age

Experiments were carried out with White Leghorn chicks to study the influence of starting diet composition on weight gain and bone growth. Increasing dietary protein level from 15 to 21% had marked influence on weight gain, tibia length and to a lesser extent, tibia weight for chicks reared to 4 and 7 wk of age. Length of tibia plateaued at lower dietary protein levels than did growth suggesting that weight gain, at a young age, is as good if not a better indication of frame size than is a measure of tiba length. While levels of dietary energy ranging from 11.29 to 12.97 MJ kg−1 did reflect changes in weight gain and tibia length, such changes were small in comparison to those noted with changes in dietary protein level. Increasing supplemental methionine level from 0.05 to 0.15% and a 50% increase in the level of calcium and available phosphorus did not enhance weight gain or frame size over the control diet. Body weight gain for the young chick was not enhanced by high dietary levels of methionine and lysine. Thus, the suggestion of rapid feather development increasing the requirement for methionine or rapid weight gain increasing the requirement for lysine at this particular age is not valid. Key words: Chickens, skeletal growth, weight gain