Plasma Methionine Concentrations Research Articles

Effects of decreased availability of sulfur amino acids in severe childhood undernutrition

In studies of glutathione (GSH) metabolism in children with severe childhood undernutrition (SCU), slower erythrocyte GSH synthesis in children with edema was associated with lower concentrations of cysteine, the rate-limiting precursor of GSH synthesis. This finding suggested a shortage of cysteine available for GSH synthesis in children with edematous SCU. The plasma concentration of methionine, the sulfur donor for cysteine synthesis, was also lower in children with edematous SCU, suggesting decreased availability of methionine for cysteine synthesis. It is also possible that reduced methionine availability will result in decreased synthesis of S-adenosylmethionine, which could lead to an overall defect in methylation reactions. This review focuses on the relationship between cysteine availability and GSH synthesis in children with SCU. It also examines whether there is an inadequate supply of cysteine in those with edematous SCU and, if so, whether this is due to a shortage of methionine due to a decreased release of methionine from protein breakdown. Finally, the review explores whether a shortage of methionine results in decreased synthesis of S-adenosylmethionine, the universal methyl donor.

Two patients with hepatic mtDNA depletion syndromes and marked elevations of S-adenosylmethionine and methionine

This paper reports studies of two patients proven by a variety of studies to have mitochondrial depletion syndromes due to mutations in either their MPV17 or DGUOK genes. Each was initially investigated metabolically because of plasma methionine concentrations as high as 15–21-fold above the upper limit of the reference range, then found also to have plasma levels of S-adenosylmethionine (AdoMet) 4.4–8.6-fold above the upper limit of the reference range. Assays of S-adenosylhomocysteine, total homocysteine, cystathionine, sarcosine, and other relevant metabolites and studies of their gene encoding glycine N-methyltransferase produced evidence suggesting they had none of the known causes of elevated methionine with or without elevated AdoMet. Patient 1 grew slowly and intermittently, but was cognitively normal. At age 7 years he was found to have hepatocellular carcinoma, underwent a liver transplant and died of progressive liver and renal failure at age almost 9 years. Patient 2 had a clinical course typical of DGUOK deficiency and died at age 8 ½ months. Although each patient had liver abnormalities, evidence is presented that such abnormalities are very unlikely to explain their elevations of AdoMet or the extent of their hypermethioninemias. A working hypothesis is presented suggesting that with mitochondrial depletion the normal usage of AdoMet by mitochondria is impaired, AdoMet accumulates in the cytoplasm of affected cells poor in glycine N-methyltransferase activity, the accumulated AdoMet causes methionine to accumulate by inhibiting activity of methionine adenosyltransferase II, and that both AdoMet and methionine consequently leak abnormally into the plasma.

Application of NMR-based metabonomics suggests a relationship between betaine absorption and elevated creatine plasma concentrations in catheterised sows

The objective of the present explorative study was to determine the absorption dynamics when feeding diets varying in types and levels of dietary fibre in a catheterised animal model. A total of six sows were fed a diet low in fibre (LF), a diet high in soluble fibre and a diet high in insoluble fibre in a repeated 3 × 3 cross-over design. Plasma samples were collected from the mesenteric artery and the portal vein to determine different absorption phases by ¹H NMR spectroscopy-based metabonomics. Time profiles were determined for plasma levels of specific metabolites and for the absorption of these metabolites from the small intestine. The LF diet resulted in a higher betaine concentration in the blood than the two high-fibre diets (P=0·008). This leads to higher plasma concentrations of methionine (P=0·0028) and creatine (P=0·020) of endogenous origin. In conclusion, the use of NMR spectroscopy for measuring nutrient uptake in the present study elucidated the relationship between betaine uptake and elevated creatine plasma concentrations.

Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome. This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence-potential precursor lesions of colorectal carcinomas-and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism. Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45-0.83), betaine: OR = 0.74; 95% CI = 0.54-1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49-0.88, and the vitamin B6 form pyridoxal 5'-phosphate (PLP): OR = 0.69; 95% CI = 0.51-0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually. High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas. In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis.

Experimental evidence of oxidative stress in plasma of homocystinuric patients: A possible role for homocysteine

Homocystinuria is an inherited disorder biochemically characterized by high urinary excretion of homocystine and increased levels of homocysteine (Hcy) and methionine in biological fluids. Affected patients usually have a variety of clinical and pathologic manifestations. Previous experimental data have shown a relationship between Hcy and oxidative stress, although very little was reported on this process in patients with homocystinuria. Therefore, in the present study we evaluated parameters of oxidative stress, namely carbonyl formation, malondialdehyde (MDA) levels, sulfhydryl content and total antioxidant status (TAS) in patients with homocystinuria at diagnosis and under treatment with a protein restricted diet supplemented by pyridoxine, folate, betaine, and vitamin B12. We also correlated plasma Hcy and methionine concentrations with the oxidative stress parameters examined. We found a significant increase of MDA levels and carbonyl formation, as well as a reduction of sulfhydryl groups and TAS in plasma of homocystinuric patients at diagnosis relatively to healthy individuals (controls). We also verified that Hcy levels were negatively correlated with sulfhydryl content and positively with MDA levels. Furthermore, patients under treatment presented a significant reduction of the content of MDA, Hcy and methionine concentrations relatively to patients at diagnosis. Taken together, the present data indicate that lipid and protein oxidative damages are increased and the antioxidant defenses diminished in plasma of homocystinuric patients, probably due to increased reactive species elicited by Hcy. It is therefore presumed that oxidative stress participates at least in part in the pathogenesis of homocystinuria.

Re-evaluation of Dietary Methionine Requirement by Plasma Methionine and Ammonia Concentrations in Surgically Modified Rainbow Trout, Oncorhynchus mykiss

This study was designed to re-evaluate the dietary methionine requirement by means of the plasma methionine and ammonia concentrations in surgically modified rainbow trout, Oncorhynchus mykiss. A total of 35 rainbow trout averaging g (initial body weight, meanSD) were randomly distributed into seven groups with five fish in each group. After 48 h of feed deprivation, each group of fish was fed one of seven L-amino acid based diets containing 0.5% cystine and graded levels of methionine (0.25, 0.40, 0.50, 0.60, 0.70, 0.80 or 0.95% of diet, dry matter bases) by intubation at 1% body weight on dry matter basis. Blood samples were taken at 0, 5 and 24 h after intubation. Post-prandial plasma free methionine concentrations (PPmet, 5 h after intubation) and post-absorptive plasma free methionine concentrations (PAmet, 24 h after intubation) of fish fed diets containing 0.60% or higher methionine were significantly (p

Reevaluation of dietary methionine requirement by plasma methionine and ammonia concentrations in surgically modified rainbow trout, Oncorhynchus mykiss

This study was designed to re-evaluate the dietary methionine requirement by means of the plasma methionine and ammonia concentrations in surgically modified rainbow trout, Oncorhynchus mykiss. A total of 35 rainbow trout averaging 505±6.5 g (initial body weight, mean±SD) were randomly distributed into seven groups with five fish in each group. After 48 h of feed deprivation, each group of fish was fed one of seven L-amino acid based diets containing 0.5% cystine and graded levels of methionine (0.25, 0.40, 0.50, 0.60, 0.70, 0.80 or 0.95% of diet, dry matter bases) by intubation at 1% body weight on dry matter basis. Blood samples were taken at 0, 5 and 24 h after intubation. Post-prandial plasma free methionine concentrations (PPmet, 5 h after intubation) and post- absorptive plasma free methionine concentrations (PAmet, 24 h after intubation) of fish fed diets containing 0.60% or higher methionine were significantly (p<0.05) higher than those of fish fed diets containing 0.50% or lower methionine. PPmet and PAmet in fish fed diets containing 0.60% or higher methionine were not significantly different except PPmet of fish fed diet containing 0.95% methionine. Post- prandial plasma ammonia concentrations (PPA, 5 h after intubation) of fish fed diets containing 0.70% or higher methionine were significantly higher than those of fish fed diets containing 0.60% or lower methionine, and PPA of fish fed diets containing 0.25 and up to 0.60% methionine were not significantly different from each other. Broken-line model analyses on PPmet, PAmet, and PPA indicated that the dietary methionine requirement of rainbow trout was between 0.59 (1.69) and 0.67 (1.91) % of diets (% dietary protein bases) when the diets contained 0.5% cystine. (Key Words : Methionine, Rainbow trout, Requirement, Intubation, Plasma, Ammonia)

Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis

Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown. We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF. This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC-tandem mass spectrometry. Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/10(6) cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05). A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown. This trial was registered at clinicaltrials.gov as NCT01150136.

Effects of Branched-Chain Amino Acid Supplementation on Plasma Concentrations of Free Amino Acids, Insulin, and Energy Substrates in Young Men

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.

Body weight and energy homeostasis was not affected in C57BL/6 mice fed high whey protein or leucine-supplemented low-fat diets

Leucine is suggested to act as nutrient signal of high-protein diets regulating pathways associated with an alleviation of metabolic syndrome parameters. However, the subject remains controversial. The aim of this study was to assess and to compare the effects of high-protein diets with dietary leucine supplementation in mice, particularly on energy homeostasis, body composition, and expression of uncoupling protein (UCP), which are suggested to decrease food energy efficiency. Male C57BL/6 mice were exposed for 14 weeks to semi-synthetic diets containing either 20% (adequate protein content, AP) or 50% whey protein (high-protein content, HP). A third group was fed the AP diet supplemented with L-leucine (AP + L) corresponding to the leucine content of the HP diet. The total fat content was 5% (w/w). Body weight gain, body composition, energy expenditure, and protein expression of UCP1 in brown adipose tissue, and UCP3 in skeletal muscle were not different between groups. In HP-fed mice, a stronger increase in blood glucose levels was detected during glucose tolerance tests compared to AP and AP + L, whereas plasma insulin was similar in all groups. Leucine supplementation did not affect glucose tolerance. Plasma cholesterol was significantly decreased in HP and AP + L when compared to AP. Plasma triglyceride concentrations were increased twofold in HP-fed mice when compared to AP + L and AP groups. Liver and skeletal muscle triglyceride and glycogen concentrations were similar in all groups. Postabsorptive plasma concentrations of branched-chain amino acids were not significantly increased after exposure to HP and AP + L diets, whereas those of lysine were decreased in HP and AP + L mice when compared to AP (P < 0.001). Plasma methionine concentrations were lower after HP intake when compared to AP and AP + L (P < 0.05). We suggest that an exposure of mice to HP diets or a corresponding leucine supplementation has no significant effect on energy homeostasis and UCP expression compared with AP diets when feeding a low-fat diet. The use of high-quality whey protein might at least in part explain the results obtained.

Increased Homocysteine in a Patient Diagnosed with Marfan Syndrome

A 53-year-old Caucasian woman was diagnosed in late childhood with Marfan syndrome according to characteristic skeletal features and bilateral lens dislocation. In addition, she has a history of nonischemic cardiomyopathy with severe left ventricular failure and atrial fibrillation, diabetes mellitus type 2, hyperlipidemia, progressive dementia, numbness in the lower extremities, and hypothyroidism following thyroidectomy for thyroid cancer. Additional findings revealed in a physical examination included an upper-to-lower segment ratio of 0.88, an arm span–to–height ratio of 1.02 (an upper-to-lower–segment ratio 1.05 are 2 of the diagnostic criteria for Marfan syndrome), an elongated face, a high arched palate, and crowded dentition. She recently underwent further laboratory testing after a cardiologist did not find 2 characteristic features of Marfan syndrome, namely an enlarged aortic root and mitral valve prolapse. Her total plasma homocysteine and methionine concentrations were increased at 198 μmol/L (reference interval, 5–15 μmol/L) and 370 μmol/L (reference interval, 10–50 μmol/L), respectively. The patient's plasma homocystine concentration was 48 μmol/L (reference interval, <2 μmol/L), and her urine homocystine concentration was also markedly increased. These biochemical abnormalities are not characteristic of Marfan syndrome. Her diagnosis was reconsidered in light of these new data. In this case, a long-standing clinical diagnosis was inconsistent with recently obtained clinical and biochemical data. The biochemical data were virtually diagnostic of homocystinuria [OMIM3 (Online Mendelian Inheritance in Man) 236200], a term historically used to describe inborn errors of metabolism characterized by excessive excretion of homocystine in urine and high concentrations of total plasma homocysteine. Homocystinuria is most commonly caused by autosomal recessive inheritance of a deficiency in cystathionine β-synthase (CBS) activity (1). The worldwide incidence has been estimated to be between 1 in 200 000 and 1 in 335 000 population (2), with the highest incidence (1 in 1800) reported in Qatar …

Effects of Amino Acid-enriched Ruminally Protected Fatty Acids on Plasma Metabolites, Growth Performance and Carcass Characteristics of Hanwoo Steers

This study was conducted to determine the effects of amino acid-enriched ruminally protected fatty acid (AARPFA) on plasma fatty acids and amino acids, growth performance and carcass characteristics of Korean native steers (Hanwoo) by simultaneous supply of fatty acids and limiting amino acids (methionine and lysine). Eighteen finishing Hanwoo steers, 18 months of age and weighing an average of 459.0±38.9 kg, were used for studies of the metabolism of plasma fatty acids and amino acids during supplementation of AARPFA. Also, 45 finishing Hanwoo steers, 16 months of age and weighing an average of 408.6±26.5 kg, were used for growth performance and carcass characteristics during supplemention of AARPFA. There were three treatments which comprised a basal diet supplemented with AARPFA at 0 g (T1), 50 g (T2) or 100 g (T3), respectively. Concentrations of saturated, unsaturated and total fatty acids in plasma were increased in T3 compared with other treatments (p<0.05). Concentrations of methionine and lysine in plasma were linearly increased with increasing levels of AARPFA (p<0.01). Average daily gain, dry matter intake and feed conversion ratio were not different among the treatments. Marbling score measured by ultra-sound scanning was higher in T3 than in T1 at 24 months of age (p<0.05). Rib eye area, back fat thickness, yield index and yield grade score were similar across the treatments. Marbling score and quality grade score were higher in T3 compared with other treatments (p<0.01). Thus, plasma fatty acids, methionine and lysine metabolism were affected by supplementing with 100 g of AARPFA which also had positive effects on marbling

Dietary Methionine Restriction with FOLFOX Regimen as First Line Therapy of Metastatic Colorectal Cancer: A Feasibility Study

The methionine (MET) dependency of tumor cells opens interesting perspectives for targeting tumor cells and potentiating chemotherapy treatment, like 5-fluorouracil (5-FU) and platinum compound. Since MET deprivation can individually potentiate the different chemotherapeutic agents used in the 48-hour combined regimen of 5-FU, leucovorin and oxaliplatin (FOLFOX) regimen, we initiated a feasibility study associating dietary MET restriction with the FOLFOX regimen in patients with metastatic colorectal cancer. Objectives: (i) To evaluate the depletion in the plasma MET concentration, and (ii) to assess the feasibility of this combination. Methods: Eleven patients were enrolled in this study. They received a median number of 3 two-week cycles of a MET-free diet (3 consecutive days) and FOLFOX6 regimen. Results: The plasma MET concentration was reduced by dietary MET restriction, with a depletion of 58% on the 1st day of MET-free diet. Indeed, we demonstrated the feasibility and good tolerance (nutritional status and toxicity) of the association of a MET-free diet with the FOLFOX regimen. Despite good compliance to the diet, this study revealed the difficulty of administering this combination during further months. Among the 4 patients evaluable for response, 3 experienced a partial response and 1 patient a disease stabilization.

The Addition of Choline to Parenteral Nutrition

Choline is a quaternary amine endogenously synthesized from the amino acid methionine or absorbed via the portal circulation. It is ubiquitous in the diet, although it has a greater presence in organ meats. Choline is an essential component of all cell membranes, and has been considered a required dietary nutrient since 1998 by the US Institute of Medicine's Food and Nutrition Board. Choline is necessary for DNA repair, mediated by its role as a methyl donor. It also serves as the precursor for the neurotransmitter acetylcholine. Evidence has accumulated that hepatic steatosis, which occurs during parenteral nutrition therapy, develops as a result of choline deficiency because endogenous production of choline from parenterally infused methionine is deficient. In addition, memory deficits and skeletal muscle abnormalities have been described, and choline deficiency appears to activate cellular apoptosis. Provision of intravenous choline ameliorates hepatic steatosis associated with parenteral nutrition infusion.

Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs

We recently showed that the developing gut is a significant site of methionine transmethylation to homocysteine and transsulfuration to cysteine. We hypothesized that sulfur amino acid (SAA) deficiency would preferentially reduce mucosal growth and antioxidant function in neonatal pigs. Neonatal pigs were enterally fed a control or an SAA-free diet for 7 days, and then whole body methionine and cysteine kinetics were measured using an intravenous infusion of [1-(13)C;methyl-(2)H(3)]methionine and [(15)N]cysteine. Body weight gain and plasma methionine, cysteine, homocysteine, and taurine and total erythrocyte glutathione concentrations were markedly decreased (-46% to -85%) in SAA-free compared with control pigs. Whole body methionine and cysteine fluxes were reduced, yet methionine utilization for protein synthesis and methionine remethylation were relatively preserved at the expense of methionine transsulfuration, in response to SAA deficiency. Intestinal tissue concentrations of methionine and cysteine were markedly reduced and hepatic levels were maintained in SAA-free compared with control pigs. SAA deficiency increased the activity of methionine metabolic enzymes, i.e., methionine adenosyltransferase, methionine synthase, and cystathionine beta-synthase, and S-adenosylmethionine concentration in the jejunum, whereas methionine synthase activity increased and S-adenosylmethionine level decreased in the liver. Small intestine weight and protein and DNA mass were lower, whereas liver weight and DNA mass were unchanged, in SAA-free compared with control pigs. Dietary SAA deficiency induced small intestinal villus atrophy, lower goblet cell numbers, and Ki-67-positive proliferative crypt cells in association with lower tissue glutathione, especially in the jejunum. We conclude that SAA deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs.

Altered amino acid homeostasis in subjects affected by fibromyalgia

Objectives To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels and FM clinical parameters. Design and methods 20 AAs were assessed in 34 FM patients and in 18 healthy volunteers by means of a modified version of the Waters picotag method. Results Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls ( P < 0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM ( P < 0.05). A significant correlation was found between FM clinical parameters and certain AAs. Conclusions Our results suggest probable defects of gut malabsorption of certain AAs in FM patients. Moreover, given the reduced Tyr CAA' ratio in FM patients, a possible impairment of the cathecolaminergic system in the FM syndrome may be suggested.

Effects of Squat Exercise and Branched-Chain Amino Acid Supplementation on Plasma Free Amino Acid Concentrations in Young Women

The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

Total sulfur amino acid requirement and metabolism in parenterally fed postsurgical human neonates

BackgroundExcept for tyrosine, the amino acid requirements of human neonates receiving parenteral nutrition (PN) have not been experimentally derived. ObjectivesThe objectives were to determine the total sulfur amino acid (TSAA) requirement (methionine in the absence of cysteine) of postsurgical, PN-fed human neonates by using the indicator amino acid oxidation (IAAO) technique with l-[1-13C]phenylalanine as the indicator. DesignFifteen postsurgical neonates were randomly assigned to receive 1 of 18 methionine intakes ranging from 10 to 120 mg · kg−1 · d−1, delivered in a customized, cysteine-free amino acid solution. Breath and urine samples were collected for the measurement of 13CO2 and amino acid enrichment. Blood samples were collected at baseline and after the test methionine infusion for the measurement of plasma methionine, homocysteine, cystathionine, and cysteine concentrations. ResultsBreakpoint analysis determined the mean TSAA requirements to be 47.4 (95% CI: 38.7, 56.1) and 49.0 (95% CI: 39.9, 58.0) mg · kg−1 · d−1 with the use of oxidation and F13CO2, respectively. ConclusionsThis is the first study to report the TSAA requirement of postsurgical, PN-fed human neonates. The estimated methionine requirement expressed as a proportion of the methionine content of current commercial pediatric PN solutions was 90% (range: 48–90%) of that found in the lowest methionine-containing PN solution.

Hypermethioninaemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency: Diagnosis in an expanded neonatal screening programme

The Expanded Newborn Screening Program (MS/MS) in the region of Galicia (NW Spain) was initiated in 2000 and includes the measurement of methionine levels in dried blood spots. Between June 2000 and June 2007, 140 818 newborns were analysed, and six cases of persistent hypermethioninaemia were detected: one homocystinuria due to cystathionine β-synthase (CβS) deficiency, and five methionine adenosyltransferase I/III (MAT I/III) deficiencies. The five cases of MAT I/III deficiency represent an incidence of 1/28 163 newborns. In these five patients, methionine levels in dried blood spots ranged from 50 to 147 μmol/L. At confirmation of the persistence of the hypermethioninaemia in a subsequent plasma sample, plasma methionine concentrations were moderately elevated in 4 of the 5 patients (mean 256 μmol/L), while total homocysteine (tHcy) was normal; the remaining patient showed plasma methionine of 573 μmol/L and tHcy of 22.8 μmol/L. All five patients were heterozygous for the same dominant mutation, R264H in the MAT1A gene. With a diet not exceeding recommended protein requirements for their age, all patients maintained methionine levels below 300 μmol/L. Currently, with a mean of 2.5 years since diagnosis, the patients are asymptomatic and show developmental quotients within the normal range. Our results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency in the Galician neonatal population, indicating a need for further studies to evaluate the impact of persistent isolated hypermethioninaemia in neonatal screening programmes.

Changes of plasma free amino acid concentrations and myofibrillar proteolysis index by starvation in non‐pregnant dry cows

ABSTRACTThe effects of 5 day starvation on urinary metabolite excretion, plasma metabolites and free amino acid concentrations in four non‐pregnant dry cows were investigated. Starvation significantly reduced (P &lt; 0.05) the bodyweight and feces weight. The plasma glucose concentration decreased (P &lt; 0.05) during days 2–5 of starvation. Starvation significantly increased (P &lt; 0.05) the plasma nonesterified fatty acid concentration. The plasma urea nitrogen concentration and urinary urea nitrogen excretion increased transiently (P &lt; 0.05) at days 1 and 2 of starvation. The plasma 3‐methlhistidine concentration was significantly higher (P &lt; 0.05) at days 2, 3 and 5 of starvation. However, the urinary 3‐methylhistidine excretion was significantly higher (P &lt; 0.05) at days 4 and 5 of starvation, not corresponding to the change in the plasma. Starvation did not change the plasma proline, methionine, lysine and total amino acid concentrations. On the other hand, starvation reduced (P &lt; 0.05) the plasma aspartic acid, serine, asparagine, glutamic acid, glutamine, alanine, tyrosine, tryptophan and histidine concentrations. Plasma glycine increased during starvation. Plasma threonine, isoleucine, leucine and branched‐chain amino acid increased (P &lt; 0.05) by prolonged starvation. The results of this study indicate that prolonged starvation accelerated myofibril protein degradation in non‐pregnant dry cows and apparently consumes most glucogenic amino acids in preference to other amino acids.