Plasma Amino Acid Data Research Articles

Plasma arginine levels in arginase deficiency in the “real world”

BackgroundDeficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories. MethodIn this study, we reported plasma arginine levels from 51 patients with arginase-1 deficiency in the database of Quest Diagnostics. The samples were collected from different US regions. ResultsThe mean plasma arginine level in these treated patients was 373 μmol/L and the median level was 368.4 μmol/L. Our data set from 30 arginase deficiency patients with plasma amino acid data from five or more collections revealed significant correlations between the levels of arginine and five other amino acids (citrulline, alanine, ornithine, glutamine, and asparagine). ConclusionDespite treatment, the arginine levels remained persistently elevated and did not change significantly with age, suggesting the current treatment regimen is inadequate to control arginine levels and underscoring the need to seek more effective treatments for this disorder.

PP-32 Do plasma amino acid levels reflect arginine metabolism in parenteral nutrition (pn) dependent very preterm infants?

Background Arginine plays an important role in several metabolic pathways as well as being a substrate for pro-tein synthesis. Arginine metabolism involves multi-com-partment processes that vary according to cell type/body organ. Enterocytes are a major site for arginine synthesis. The key amino acid (AA) metabolites of arginine synthesis pathways in the enterocytes of very preterm infants (VPIs) include glutamine, glutamate and proline with interme-diates ornithine and citrulline. The key arginine degrada-tion AA metabolite in the liver is ornithine. In contrast to these metabolically active AAs, histidine is presumed to be a metabolically inert AA and hence probably a useful indicator of non-metabolic factors (e.g. renal elimination). Newborn infants are dependent on enteral milk proteins for the AAs required for enterocyte arginine synthesis. However VPIs are dependent on parenteral nutrition (PN) and therefore parenteral AA for the first 2 weeks of life un-til milk feeds are established. Methods Secondary analysis was performed on the plasma AA data collected during a previously published randomised controlled trial.1 Plasma AA were collected in the second week of life in infants randomised to receive either 3.2 g/kg/d (standard) or 4.3 g/kg/d (high dose) par-enteral AA.2 A Spearman’s correlation analysis was run on the plasma data for the AA subgroups involved in argi-nine metabolic pathways to assess their relationship with arginine in the VPI population. The data also underwent multivariate regression analysis (combining both groups) to test if any of these AA significantly predicted plasma arginine levels. Results Plasma AA levels were performed on median (IQR) day 9 (8-10) in both groups. Mean (95% confidence intervals) plasma arginine levels were 41 (25-57) and 35 (22-46) micromol/litre in the high and standard AA dose groups respectively (p=0.21) well below the reference range minimum (57µmol/L). Data analysis showed that arginine had the strongest positive correlation with or-nithine, r=0.602, n=107, p Conclusion Plasma ornithine, glutamate and histidine are significant predictors of plasma arginine in PN depen-dent VPIs. This indicates that there are both metabolic and non-metabolic factors that play a role in determination of plasma arginine levels.

Nitrogen Retention and Plasma Amino Acid Responses in Mature Geldings Fed Three Dietary Concentrations of Lysine

Six mature Quarter Horse geldings (age, 11.5 ± 4.7 years; body weight [BW], 526 ± 9.2 kg) were used in a replicated 3 × 3 Latin square design to determine the effects of three dietary lysine (Lys) levels on nitrogen (N) retention and plasma amino acid (AA) concentrations. The geldings were fed a basal diet of concentrate and Bermuda grass hay supplemented with synthetic essential amino acids (EAA) to meet estimated requirements for EAA. Geldings were fed one of three dietary treatments: (1) a basal diet deficient in Lys (L−; 0.027 g of Lys•kg−1 BW•d−1); (2) a basal diet supplemented with synthetic Lys to meet National Research Council (NRC; 2007) requirements (L+; 0.036 g of Lys•kg−1 BW•d−1); or (3) a basal diet supplemented at twice the recommended Lys requirement (2 × L; 0.070 g Lys•kg−1 BW•d−1). Horses fed the 2 × L diet had higher N intakes (P = .0056) than horses fed either the L− or L+ diet. However N retention (P = .63) was not different between treatments. Plasma Lys was greater (P < .0001) in 2 × L than L− and L+ diets. Plasma threonine (Thr; P < .01), methionine (Met; P = .03), and total plasma non-EAA (P < .05) concentrations decreased as dietary Lys increased. These results suggest N retention is not a good response criterion for evaluating the AA requirements of mature horses. However, plasma AA data indicated more efficient use of Thr and Met when horses were fed dietary Lys in concentrations greater than the current requirement recommended by the Nutrient Requirements of Horses (National Research Council, 2007).

Measurement of plasma amino acids by Ultraperformance® Liquid Chromatography

Since the early 1960s, quantitative amino acid analysis (AAA) has traditionally been performed using ion-exchange chromatography with post-column ninhydrin derivatization. This established technology has many advantages, including relatively low cost of operation and ease of use. However, analysis times of 120+ min and high maintenance requirements make this technology unsuitable for the modern clinical laboratories with a requirement for rapid turnaround times. The work described here is a summary of our experiences with a new approach to full profile analysis of physiological amino acids. Amino acids were derivatized in batches with a proprietary reagent, AccQTag®, which reacts with primary and secondary amines. The derivatized amino acids were separated using Ultraperformance® Liquid Chromatography (UPLC). In a prospective method comparison, quantitative plasma amino acid data obtained from approximately 170 patient samples using both the UPLC method and a traditional ion-exchange chromatography amino acid analyzer were evaluated. The data obtained from the two methods were found to agree well. Correlation coefficients for the most important amino acids seen in inborn errors of metabolism, such as phenylalanine, tyrosine and branched chain amino acids varied from 0.8658 to 0.9932 with minor slope biases. This approach also reduced the run time from 120 to 45 min per sample using a sample volume of 0.1 mL, compared to the 0.5 mL volume required for ion-exchange chromatography. This new approach for the full profile analysis of physiological amino acids has been shown to be a viable substitute for current ion-exchange methodologies. It provides substantial benefits including significant reductions in runtime and necessary sample volume for the investigation and monitoring of patients with metabolic disorders and for nutritional management of a variety of patients.

Effects of supplying leucine and methionine to early-lactating cows fed silage-concentrate based diets with a calculated deficiency in leucine and methionine

In a 2 〈 2 factorial approach the productive and metabolic response of 24 multiparous Brown Swiss cows fed rations calculated to be deficient in leucine (0.9-fold of requirements) and methionine (0.8-fold) to supplementation either of one or both of these amino acids were investigated. On a dry matter basis the rations consisted of 29% grass silage, 20% maize silage, 6% hay, and 45% concentrate. Blood plasma amino acid data confirmed the intended difference in metabolic supply of leucine and methionine keeping a low variation in the plasma levels of the other essential amino acids, particularly lysine. Live weight, milk yield as well as content and amount of milk fat were not affected by the treatments. Content and amount of milk protein were significantly reduced relative to initial level without additional methionine. Nutrient digestibility and nitrogen balance remained widely unchanged by the supplementations. Except of plasma aspartate amino transferase, cholesterol, creatinine and ornithine, which responded to methionine, hormones, enzyme activities as well as plasma, urine and milk metabolites were not systematically influenced by leucine and methionine sup- ply. The present results gave clearer indications for a deficiency in methionine than in leucine.

Impact of a Camp Experience on Phenylalanine Levels, Knowledge, Attitudes, and Health Beliefs Relevant to Nutrition Management of Phenylketonuria in Adolescent Girls

Objective To evaluate the effectiveness of an education intervention in a summer camp setting on knowledge, attitudes, and health beliefs regarding metabolic control of phenylketonuria and dietary compliance. Design An observational study of a weeklong metabolic camp for adolescent girls with phenylketonuria (PKU) who were followed up over the course of 1 year. Observations also were made in 3 subsequent years of camp. Intervention The camp experience consisted of diet and disease education, sessions on reproductive development, and recreation. Group discussions on attitudes and perceptions about PKU related to dietary compliance were held with nutritionists and a pediatric psychologist. Outcome measures Biochemical and psychological data were collected on the first and last days of the camp to assess short-term effects of the intervention, then at quarterly intervals during the year to determine the long-term impact of the camp. Precamp and Postcamp plasma amino acid data for the subsequent 3 years were also collected. Subjects/setting Analyses were based on 13 adolescent girls with PKU in the first year of a camp at Emory University in Atlanta, Ga, and compared with data from 11 additional campers enrolled the second year, 8 in the third year, and 7 in the fourth year. Mean age±standard deviation of first-year campers was 13±2 years, mean IQ±standard deviation was 98±16, and 9 of 13 girls had menstruated. Statistical analyses performed Short-term effects of the intervention were computed by comparing mean levels of response from the baseline period to those from the last day of camp using t tests for dependent samples. Repeated-measures analysis of variance was used to assess the long-term effects of the camp experience over the course of a year at regular quarterly intervals. Results Short-term effects of the education intervention were significant reductions in dietary phenylalanine intake, plasma phenylalanine levels, and perceived isolation. However, these effects progressively returned to baseline levels over the course of a year. The significant short- and long-term effects of increased knowledge of diet and disease persisted throughout the study period. Applications/conclusions Short-term effects of the education intervention resulted in improved metabolic control associated with improved attitudes, increased knowledge of diet and disease, increased perceived support, and decreased barriers to dietary compliance in a camp setting. J Am Diet Assoc. 2000;100:797-803.

The plasma amino acid profile and its relationships to standard quantities of liver function in infants and children with extrahepatic biliary atresia and preterminal liver cirrhosis.

The absolute and relative concentrations of 16 plasma amino acids in 48 mostly dystrophic infants and children (median of age 1 1/2 years) with extrahepatic biliary atresia and mainly stable preterminal cirrhosis were compared with those of controls. Patient plasma amino acid data were analysed statistically for diagnostic usefulness and correlated with standard biochemical quantities of liver function and of liver perfusion. In the patients the total amounts of non-essential and essential amino acids were reduced by 19% and with the same significance (p < 0.0005). Plasma tyrosine was increased (+40%), while taurine (-44%) and branched chain amino acids (+28.8% to -34.7%) were decreased. Methionine values varied widely. In the molar fractional plasma amino acid profile, only alanine, valine, and leucine were decreased, while threonine, methionine, tyrosine, phenylalanine, ornithine, and serine were increased. Discriminate function analysis showed that the plasma amino acid data discriminated 93.8% of the patients from controls. The concentrations of some amino acids in plasma seemed to have been influenced by protein-calorie deficiency in the patients. The valine/tyrosine ratio and the Fischer index (ratio branched chain/aromatic amino acids) were significantly reduced in the patients versus controls (1.54 +/- 0.55 vs 3.08 +/- 0.55 and 1.66 +/- 0.39 vs 3.00 +/- 0.48). A number of significant correlations (range of r: 0.37-0.59, p < 0.05, 30-48 data pairs) were calculated between plasma amino acid data and several standard biochemical quantities of liver function. The statistical analyses also showed that the Fischer index began to decrease gradually and linearly early in the progression of liver failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma amino acid pattern in normal term breast-fed infants

It seems reasonable that amino acid solutions used for parenteral nutrition should lead to a plasma amino acid pattern that resembles that of the normal, postprandial concentrations of amino acids in breast-fed infants. Previous studies of postprandial plasma amino acid concentrations have been inadequate for several reasons, such as consumption of infant formulas of different composition, inadequate intake of human milk, varying times of postprandial plasma sampling, a wide range of infants studied, and incomplete data sets lacking one or more nutritionally important amino acids? -4 Our study was designed to obtain complete plasma amino acid data for the breast-fed infant. It has been suggested that this normal plasma amino acid pattern represents the optimal pattern for supporting growth, and possibly for estimating repletion of the nutritionally compromised patients. METHODS Subjects were infants of multiparous women 15 to 28 years of age (mean 22.9 years), 20 Hispanic and one black, who met the following entry criteria: mothers of normal nutriture as assessed by using appropriate weight and height charts; term neonates appropriate for age, with normal weight/length ratio using the ponderal index of Miller and HassaneinS; both mothers and infants healthy; informed consent; infants exclusively breast-fed during the first month of life. This study was approved by the Research Committee of the Los Angeles County-University of Southern California Medical Center and the USC School of Medicine.

Food and metabolism in infancy. The relationships of plasma amino acids as an indicator of the adequacy of protein intake.

Heird, W. C., Dell, R. B. and Winters, R. W. (Department of Pediatrics and Institute of Human Nutrition, Columbia University College of Physicians &amp; Surgeons, New York). Food and metabolism in infancy. Acta Paediatr Scand, Suppl. 299: 24, 1982.—Published plasma amino acid data from normally‐growing term and preterm infants fed varying quantities of protein as well as proteins of varying quality were examined in an effort to assess the efficacy of these data as indicators of the adequacy and/or inadequacy of protein intake. Although the absolute plasma concentrations of most amino acids vary considerably, all sets of data from term infants, with exception of those from infants fed inadequate protein or inordinately large quantities of protein, when expressed as the ratio of TEAA/TAA and ind. EAA/TEAA, are remarkably similar. Despite variations in absolute plasma amino acid concentrations of as much as 60 %, for example, fasting and postprandial TEAA/TAA and ind. EAA/TEAA ratios are similar. The plasma TEAA/TAA ratio of infants fed a low protein intake (1.1 g/kgd) is low but this ratio is similar in plasma of infants fed either 3.0‐3.5 g/kgd or 9 g/kgd. Ind. EAA/TEAA ratios, on the other hand, are the same in plasma of infants fed either 1.1 or 3.0‐3.5 g/k ‐ d but some are dramatically higher in plasma of infants fed a protein intake of 9.0 g/kgd. Although ind. EAA/TEAA ratios vary somewhat as a function of the quality of protein intake, this variation is not nearly as great as that of the intake ratios. Finally, the relatively constant plasma ratios of TEAA/TAA and ind. EAA/TEAA are remarkably similar to those of the tissue deposited during normal growth. These observations support the hypothesis that the various enteric, hepatic and other mechanisms which determine the amino acid composition of plasma have as their target these relationships among various amino acids rather than absolute plasma concentrations of the various amino acids. If so, it follows that maintenance of these relationships may be an important factor for optimal protein synthesis. If these hypotheses prove to be correct, an appropriate criteria for efficacy of alternative feeding regimens chosen for the infant who is not or cannot be breast fed is whether or not this regimen overwhelms the mechanisms responsible for maintaining these apparent relationships among the amino acids in plasma.

Aspects of Threonine and Glycine Metabolism in the Chick &lt;i&gt;(Gallus domesticus)&lt;/i&gt;

Two assays were conducted with young chicks to assess the nutritional implications of the degradation of excess threonine to glycine and acetaldehyde. In the first experiment, 1.0% threonine added to a semi-purified diet depressed growth and food intake severely, and also lowered the circulating levels of glycine. In the second assay, 0.5% threonine added to a crystalline amino acid diet lacking in glycine and serine but, containing 0.3% threonine, enhanced weight gain and efficiency of food conversion but had no appreciable influence on plasma glycine levels. Addition of 1.0% threonine to the crystalline amino acid diet did not augment growth further. Combinations of 1.2% glycine and threonine supplements increased growth markedly, 0.5% additional threonine producing the best performance. The plasma amino acid data, therefore, suggest that threonine is not readily degraded to glycine and, therefore, cannot act as a precursor of this amino acid for the chick.

Effect of Feed Consumption on Plasma Amino Acid Concentrations in Lambs

Increased consumption of a corn-soybean meal diet from maintenance through increments to approximately 2.5 times maintenance increased weight gain, gain :feed, plasma urea-nitrogen, and concentrations of most plasma free-amino acids. The failure of plasma sulfur-containing amino acids and histidine to increase with increased diet consumption may indicate that these amino acids were limiting performance. Since it influences plasma amino acid concentrations, feed intake is a major factor in interpretation of plasma amino acid data.

Amino acid interactions in chick nutrition. 2. Interrelationships between leucine, isoleucine and valine.

Synopsis The nature of interactions between leucine, isoleucine and valine has been examined in the young chick. In a preliminary experiment excess leucine was added to a diet limiting in isoleucine. The consequent growth depression was partially reversed by additional isoleucine. The plasma amino acid data indicated that the circulating levels of isoleucine and valine were lowered by the surplus load of leucine. Addition of excess leucine to another diet prevented the growth response to the first limiting amino acid, methionine, but permitted the response if this diet were adequately supplemented with isoleucine. Another diet was prepared in which the level of isoleucine was limiting and the level of valine marginally adequate. The growth retardations following addition of large quantities of leucine were reversed primarily by valine. Complete restoration of growth occurred when both valine and isoleucine were present as additional supplements. Excess methionine added to a diet limiting in valine inhibit...