scholarly journals Phenylalanine requirement in children with classical PKU determined by indicator amino acid oxidation

2002 ◽  
Vol 283 (6) ◽  
pp. E1249-E1256 ◽  
Author(s):  
Glenda Courtney-Martin ◽  
Rachelle Bross ◽  
Mahroukh Raffi ◽  
Joe T. R. Clarke ◽  
Ronald O. Ball ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Oxidation ◽  
Phenylalanine Concentration ◽  
Two Phase ◽  
Amino Acid Oxidation ◽  
Blood Phenylalanine ◽  
Plasma Phenylalanine ◽  
Crossover Analysis ◽  
The Mean ◽  
The Difference

Dietary restriction of phenylalanine is the main treatment for phenylketonuria (PKU), and current estimates of requirements are based on plasma phenylalanine concentration and growth. The present study aimed to determine more precisely the phenylalanine requirements in patients with the disease by use of indicator amino acid oxidation, withl-[1-13C]lysine as the indicator. Breath13CO2 production (F13 co 2) was used as the end point. Finger-prick blood samples were also collected for measurement of phenylalanine to relate phenylalanine intake to blood phenylalanine levels. The mean phenylalanine requirement, estimated using a two-phase linear regression crossover analysis, was 14 mg · kg−1 · day−1, and the safe population intake (upper 95% confidence interval of the mean) was found to be 19.5 mg · kg−1 · day−1. A balance between phenylalanine intake and the difference between fed and fasted blood phenylalanine concentration was observed at an intake of 20 mg · kg−1 · day−1. The similarity between these two values (19.5 and 20 mg · kg−1 · day−1) suggests that the maximal phenylalanine intake for children with PKU should be no higher than 20 mg · kg−1 · day−1.

scholarly journals Adult dogs of different breed sizes have similar threonine requirements as determined by the indicator amino acid oxidation technique

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Wilfredo D Mansilla ◽  
Lisa Fortener ◽  
James R Templeman ◽  
Anna K Shoveller
Keyword(s):  
Amino Acid ◽  
Basal Diet ◽  
Acid Oxidation ◽  
Total Production ◽  
Experimental Diet ◽  
Two Phase ◽  
Deficient Diet ◽  
Amino Acid Oxidation ◽  
The Mean ◽  
Labrador Retrievers

Abstract Threonine (Thr) requirements for immature (growing) Beagles have been determined, but little knowledge is available on Thr requirements for maintenance in mature dogs. Moreover, differences of Thr requirements among different breeds or sizes of adult dogs have not been investigated. The objective of the present study was to determine Thr requirements in adult dogs of three different breeds using the indicator amino acid oxidation (IAAO) technique. In total, 13 adult dogs were used, 4 Miniature Dachshunds (5.8 ± 0.4 kg body weight [BW]; 3 spayed and 1 neutered), 4 spayed Beagles (9.3 ± 0.6 kg BW), and 5 neutered Labrador Retrievers (30.5 ± 1.7 kg BW). Dogs were fed a Thr-deficient diet (Thr = 0.23%) and randomly allocated to receiving one of seven concentrations of Thr supplementation (final Thr concentration in experimental diets was 0.23%, 0.33%, 0.43%, 0.53%, 0.63%, 0.73%, and 0.83%; as fed basis) for 2 d. After 2 d of adaptation to the experimental diets, dogs underwent individual IAAO studies. During the IAAO studies, total daily feed was divided into 13 equal meals; at the sixth meal, dogs were fed a bolus of l-[1-13C]-Phenylalanine (Phe) (9.40 mg/kg BW), and thereafter, l-[1-13C]-Phe (2.4 mg/kg BW) was supplied with every meal. Before feeding the next experimental diet, dogs were fed a Thr-adequate basal diet for 4 d (Thr = 0.80% as fed basis) in known amounts that maintained individual dog BW. Total production of 13CO2 during isotopic steady state was determined by enrichment of 13CO2 in breath samples and total production of CO2 measured using indirect calorimetry. The mean requirements for Thr, defined as the breakpoint, and the 95% confidence interval (CI) were determined using a two-phase linear regression model. For Miniature Dachshunds, the two-phase model was not significant, and Thr requirements could not be determined. Mean Thr requirements for Beagles and Labradors were 72.2 and 64.1 mg/kg BW on an as-fed basis, respectively. The requirement for Thr between these two dog breeds was not different (P > 0.10). Thus, the data for Beagles and Labradors were pooled and a mean requirement for Thr was determined at 66.9 mg/kg BW, and the 95% CI was estimated at 84.3 mg/kg BW. In conclusion, estimated Thr requirements for Beagles and Labradors did not differ, and these recommendations are higher than those suggested by NRC (2006) and AAFCO (2014) for adult dogs at maintenance.

Tyrosine requirements in children with classical PKU determined by indicator amino acid oxidation

2000 ◽  
Vol 278 (2) ◽  
pp. E195-E201 ◽  
Author(s):  
Rachelle Bross ◽  
Ronald O. Ball ◽  
Joe T. R. Clarke ◽  
Paul B. Pencharz
Keyword(s):  
Amino Acid ◽  
Pediatric Population ◽  
Protein Composition ◽  
Break Point ◽  
Acid Oxidation ◽  
Amino Acid Oxidation ◽  
Equal Dose ◽  
Dose Infusion ◽  
Normal Humans ◽  
The Mean

Tyrosine (Tyr) is an essential amino acid in phenylketonuria (PKU) because of the limited hydroxylation of phenylalanine (Phe) to Tyr. The recommended intakes for Tyr in PKU are at least five times the recommended phenylalanine intakes. This suggests that Phe and Tyr contribute ∼20 and 80%, respectively, of the aromatic amino acid (AAA) requirement (REQ). In animals and normal humans, dietary Tyr was shown to spare 40–50% of the Phe requirement, proportions that reflect dietary and tissue protein composition. We tested the hypothesis that the Tyr REQ in PKU would account for 45% of the total AAA REQ by indicator amino acid oxidation (IAAO). Tyr REQ was determined in five children with PKU by examining the effect of varying dietary Tyr intake on lysine oxidation and the appearance of 13CO2 in breath (F13CO2) under dietary conditions of adequate energy, protein (1.5 g ⋅ kg− 1 ⋅ day− 1), and phenylalanine (25 mg ⋅ kg− 1 ⋅ day− 1). Lysine oxidation and F13CO2 were determined using a primed 4-h oral equal-dose infusion ofl-[1-13C]lysine. Lysine oxidation and F13CO2 decreased linearly as Tyr intake increased, to a break point that was interpreted as the mean dietary Tyr requirement (16.3 and 19.2 mg ⋅ kg− 1 ⋅ day− 1, respectively). At Tyr intakes of >16.3 and 19.2 mg ⋅ kg− 1 ⋅ day− 1, lysine oxidation and F13CO2, respectively, were low and constant. This represents 40.4 and 44.4%, respectively, of the total AAA intake. The current recommendations for Tyr intake in PKU patients appear to be overestimated by a factor of ∼5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.

scholarly journals Tryptophan Requirement in School-Age Children Determined by the Indicator Amino Acid Oxidation Method is Similar to Current Recommendations

2019 ◽  
Vol 149 (2) ◽  
pp. 280-285 ◽  
Author(s):  
Abeer Al-mokbel ◽  
Glenda Courtney-Martin ◽  
Rajavel Elango ◽  
Ronald O Ball ◽  
Paul B Pencharz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Intake ◽  
School Age Children ◽  
Acid Mixture ◽  
Acid Oxidation ◽  
School Age ◽  
Mixed Effect ◽  
Effect Change ◽  
Amino Acid Oxidation ◽  
The Mean

ABSTRACT Background The requirement for dietary tryptophan in school-age children has never been empirically derived. Objective The objective of our study was to determine the tryptophan requirement of school-age children using the indicator amino acid oxidation technique. Methods Volunteer healthy school-age children, between 8 and 12 y, were enrolled and the oxidation of l-[13C]-phenylalanine to 13CO2 measured in response to graded intakes of dietary tryptophan. Seven children (3 boys, 4 girls) participated in the study and received randomly assigned tryptophan intakes ranging from 0.5 to 9.75 mg.kg-1.d-1 for a total of 36 studies. The diets provided energy at 1.5 times each subject's resting energy expenditure and were isocaloric. Protein was provided as an amino acid mixture on the basis of the egg protein pattern, and phenylalanine and tyrosine were maintained constant across the protein intake concentrations at 25 and 40 mg.kg−1.d−1. All subjects were adapted for 2 d before the study day to a protein intake of 1.5 g.kg−1.d−1. The mean tryptophan requirement was determined by applying a mixed-effect change-point regression analysis to F13CO2 (label tracer oxidation in 13CO2 breath) which identified a breakpoint in the F13CO2 in response to graded amounts of tryptophan. Results The mean [estimated average requirement (EAR)] and upper 95% CI, (approximating the RDA) of tryptophan requirements were estimated to be 4.7 and 6.1 mg.kg−1.d−1, respectively. Conclusion Our results are similar to the current recommended EAR and RDA of 5 and 6 mg.kg−1.d−1 for healthy growing children based on the factorial calculation. Clinical Trials Registration No. NCT02018588.

scholarly journals Lysine requirements in small, medium, and large breed adult dogs using the indicator amino acid oxidation technique1

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Katja A K Sutherland ◽  
Wilfredo D Mansilla ◽  
Lisa Fortener ◽  
Anna K Shoveller
Keyword(s):  
Amino Acid ◽  
Feed Intake ◽  
Dry Matter ◽  
National Research Council ◽  
Acid Oxidation ◽  
Total Production ◽  
Test Diet ◽  
Two Phase ◽  
Amino Acid Oxidation ◽  
Matter Basis

Abstract There is a lack of knowledge regarding the lysine (Lys) requirements of mature dogs and whether there are breed differences. The present study aimed to determine the Lys requirement in three breeds of mature dogs using the indicator amino acid oxidation (IAAO) technique. Thirteen adult dogs were used, four Miniature Dachshunds (5.39 ± 0.71 kg; 1.05 ± 0.02 yr old, mean ± SD), four Beagles (8.09 ± 0.40 kg; 5.03 ± 0.09 yr old, mean ± SD), and five Labrador Retrievers (29.42 ± 2.04 kg; 3.30 ± 0.69 yr old, mean ± SD). After 14 d of adaptation to a basal extruded kibble diet, dogs were fed a test diet mildly deficient in Lys (Lys concentration = 0.36%) at 17 (Miniature Dachshunds) or 13 g/kg body weight (BW; Beagles and Labradors) for 2 d. The test diet was supplemented with one of seven isonitrogenous Lys–Ala solutions, resulting in a final dietary Lys concentration of 0.36%, 0.40%, 0.44%, 0.50%, 0.54%, 0.58%, and 0.62% (as-fed basis). Dogs received dietary concentrations of Lys in random order and no dog received the same order. Following 2 d of adaptation to the experimental diets, the dogs underwent IAAO studies. During the IAAO studies, total daily feed was divided in 13 equal meals. At the sixth meal, dogs were fed a bolus of L-[1-13C]-Phe (9.40 mg/kg BW); thereafter, L-[1-13C]-Phe was supplied with every meal (2.4 mg/kg BW). Total production of 13CO2 (F13CO2) during isotopic steady state was determined by enrichment of 13CO2 of breath samples and total production of CO2, measured using indirect calorimetry. A two-phase linear regression model was used to derive the mean Lys requirement, defined as the breakpoint, and the upper 95% confidence limit was calculated as the recommended allowance (RA) for Lys intake. For Miniature Dachshunds, the study was repeated with a feed intake of 14 g/kg BW, but Lys requirements could not be determined at either feed intake, suggesting a requirement below the lowest concentration and intake. Mean Lys requirements for Beagles and Labradors were 0.455% (59.16 mg/kg BW) and 0.440% (57.19 mg/kg BW), respectively, on a dry matter basis. Pooling the data for these breeds provides a mean estimate of the Lys requirement at 0.448% (58.21 mg/kg BW) with an upper 95% CL of 0.526% (68.41 mg/kg BW) on a dry matter basis. In conclusion, the Lys requirements of Beagles and Labradors are similar, while the requirement for Miniature Dachshunds is undetermined and likely lower. The estimated Lys requirement for Beagles and Labradors is higher than the National Research Council recommendation.

scholarly journals Dietary phenylalanine requirements during early and late gestation in healthy pregnant women

2019 ◽  
Vol 111 (2) ◽  
pp. 351-359 ◽  
Author(s):  
Madeleine A Ennis ◽  
Betina F Rasmussen ◽  
Kenneth Lim ◽  
Ronald O Ball ◽  
Paul B Pencharz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Early Pregnancy ◽  
Resting Energy Expenditure ◽  
Late Pregnancy ◽  
Late Gestation ◽  
Acid Oxidation ◽  
Amino Acid Oxidation ◽  
Dietary Requirements ◽  
Isotope Ratio Mass Spectrometer ◽  
The Mean

ABSTRACT Background Phenylalanine is an indispensable amino acid and, via tyrosine, is the precursor for the neurotransmitters dopamine, norepinephrine, and epinephrine. Currently, dietary requirements for phenylalanine during pregnancy are unknown. Objectives This study's aim was to determine phenylalanine requirements (in the presence of excess tyrosine) during early and late gestation using direct amino acid oxidation (DAAO; with l-[1-13C]phenylalanine) and indicator amino acid oxidation (IAAO; with l-[1-13C]leucine). Methods Twenty-three healthy women (age: 30.4 ± 3.1 y, mean ± SD) were studied at a range of phenylalanine intakes (5.5–30.5 mg · kg−1 · d−1 in early and late pregnancy using DAAO, and 2.5–30.5 mg · kg−1 · d−1 in late pregnancy using IAAO) for a total of 76 study days. Test intakes were provided as 8 isocaloric and isonitrogenous meals with 1.5 g · kg−1 · d−1 protein and energy at 1.7 times the measured resting energy expenditure. Breath samples were analyzed on an isotope ratio mass spectrometer for 13C enrichment. Phenylalanine requirement was determined using a 2-phase linear regression crossover model to identify a breakpoint in 13CO2 production (representing the mean requirement) in response to phenylalanine intakes. Results Phenylalanine requirement during early pregnancy was determined to be 15 mg · kg−1 · d−1 (95% CI: 10.4, 19.9 mg · kg−1 · d−1); during late pregnancy, it was determined to be 21 mg · kg−1 · d−1 by DAAO (95% CI: 17.4, 24.7 mg · kg−1 · d−1) and IAAO (95% CI: 10.5, 32.2 mg · kg−1 · d−1). Conclusions Our results suggest a higher requirement (40%) for phenylalanine during late pregnancy than during early pregnancy. Moreover, the early pregnancy requirements are higher than the previous adult male requirement (9.1 mg · kg−1 · d−1; 95% CI: 4.6, 13.6 mg · kg−1 · d−1), although the 95% CIs overlap. Both DAAO and IAAO methods provided similar breakpoints in late pregnancy, showing that the DAAO method was appropriate even though low phenylalanine intakes could not be tested. These results have potential implications for gestation stage–specific dietary phenylalanine recommendations in future. This trial was registered at clinicaltrials.gov as NCT02669381.

Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine

1993 ◽  
Vol 264 (4) ◽  
pp. E677-E685 ◽  
Author(s):  
G. A. Zello ◽  
P. B. Pencharz ◽  
R. O. Ball
Keyword(s):  
Amino Acid ◽  
Break Point ◽  
World Health ◽  
Acid Oxidation ◽  
Adult Males ◽  
Plasma Phenylalanine ◽  
The World ◽  
Amino Acid Requirements ◽  
The Mean ◽  
Health Organization

Lysine requirement was determined in seven adult males by examining the effect of varying dietary lysine intake on phenylalanine flux and oxidation under dietary conditions of adequate energy and phenylalanine (14 mg.kg-1 x day-1) and excess tyrosine (40 mg.kg-1 x day-1). Phenylalanine flux was determined from primed, constant intravenous infusions of L-[1-13C]phenylalanine (1.2 mg.kg-1 x day-1) and L-[ring-2H5]phenylalanine (0.5 mg.kg-1 x day-1) and measurement of isotopic enrichments of phenylalanine in plasma. Phenylalanine flux was not affected by graded increases in dietary lysine intake or by the isotope infused. Mean phenylalanine conversion to tyrosine was low (3.4%) and not significantly affected by lysine intake. Phenylalanine oxidation, estimated from the rate of 13CO2 released in expired air during the infusion of L-[1-13C]phenylalanine, decreased linearly as lysine intake increased to a break point that was interpreted as the mean dietary lysine requirement (37 mg.kg-1 x day-1). At lysine intakes of > 37 mg.kg-1 x day-1 phenylalanine oxidation was low and constant. Plasma lysine concentrations supported this estimate of requirement. These data show that: 1) indicator amino acid oxidation can be used as a new method to determine amino acid requirements of humans and 2) the lysine requirement of adult males is three times greater than the World Health Organization recommendation of 12 mg.kg-1 x day-1.

Total branched-chain amino acids requirement in patients with maple syrup urine disease by use of indicator amino acid oxidation with l-[1-13C]phenylalanine

2004 ◽  
Vol 287 (1) ◽  
pp. E142-E149 ◽  
Author(s):  
Roya Riazi ◽  
Mahroukh Rafii ◽  
Joe T. R. Clarke ◽  
Linda J. Wykes ◽  
Ronald O. Ball ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Maple Syrup Urine Disease ◽  
Branched Chain Amino Acids ◽  
Acid Oxidation ◽  
Maple Syrup ◽  
Amino Acid Oxidation ◽  
Urine Disease ◽  
The Mean ◽  
Branched Chain

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by defects in the mitochondrial multienzyme complex branched-chain α-keto acid dehydrogenase (BCKD; EC 1.2.4.4 ), responsible for the oxidative decarboxylation of the branched-chain ketoacids (BCKA) derived from the branched-chain amino acids (BCAA) leucine, valine, and isoleucine. Deficiency of the enzyme results in increased concentrations of the BCAA and BCKA in body cells and fluids. The treatment of the disease is aimed at keeping the concentration of BCAA below the toxic concentrations, primarily by dietary restriction of BCAA intake. The objective of this study was to determine the total BCAA requirements of patients with classical MSUD caused by marked deficiency of BCKD by use of the indicator amino acid oxidation (IAAO) technique. Five MSUD patients from the MSUD clinic of The Hospital for Sick Children participated in the study. Each was randomly assigned to different intakes of BCAA mixture (0, 20, 30, 50, 60, 70, 90, 110, and 130 mg·kg−1·day−1), in which the relative proportion of BCAA was the same as that in egg protein. Total BCAA requirement was determined by measuring the oxidation of l-[1-13C]phenylalanine to 13CO2. The mean total BCAA requirement was estimated using a two-phase linear regression crossover analysis, which showed that the mean total BCAA requirement was 45 mg·kg−1·day−1, with the safe level of intake (upper 95% confidence interval) at 62 mg·kg−1·day−1. This is the first time BCAA requirements in patients with MSUD have been determined directly.

scholarly journals PSXI-31 Program Chair Poster Pick: Determination of the threonine requirement in adult and senior Labrador Retrievers using the indicator amino acid oxidation technique

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 321-322
Author(s):  
Jordan T Weil ◽  
Jessica L Varney ◽  
Jason W Fowler ◽  
Craig N Coon
Keyword(s):  
Amino Acid ◽  
Control Diet ◽  
Genetic Selection ◽  
Isotope Ratio Mass Spectrometry ◽  
Acid Oxidation ◽  
Amino Acid Oxidation ◽  
Amino Acid Requirements ◽  
Indispensable Amino Acids ◽  
Nutrient Profiles ◽  
Labrador Retrievers

Abstract Although nutrient profiles for canines have been developed in the past, the need to update amino acid (AA) requirements has gained importance as genetic selection changes the recommended nutrients. Correctly feeding AA to canines can have enormous effects, considering a deficiency or excess of such nutrient can lead to weight loss, disease, or in some cases, death. Amino acid requirements can be determined through the nitrogen balance or indicator amino acid oxidation (IAAO) methods. In this experiment, the IAAO technique was used to determine the threonine (Thr) requirement in Labrador retrievers. A total of six dogs (6 adult and 6 senior) were subjected to six diets with varying levels of Thr, ranging from deficient to excess. Diets were formulated to 1.6x NRC values for all indispensable amino acids. The control diet was fed for two days, followed by a day in which the test diet was fed, a tracer AA was supplied, and breath samples were collected. On test day, a priming dose of L-[1-13C]phenylalanine (Cambridge Isotope Laboratories, Inc.) based on the subject’s body weight was first supplied, followed by [1-13C]Phe doses every thirty minutes, spanning a four hour period. A respiration mask was placed on each subject every thirty minutes (Oxymax, Columbus Instruments), 13CO2 was collected, and enrichment was determined by isotope ratio mass spectrometry (IRMS). Results for IRMS were converted to atom percent excess (APE) and analyzed using a piecewise model of best fit (JMP® Pro 15). The segmented line regression showed that the Thr mean and population requirements were determined to be 1.21 ± 0.24 and 0.92 ± 0.17 g/1000kcal (mean ± 2SD) for adult and senior dogs, respectively. As the pet food industry becomes more specialized in diets relating to aging, and diseased canines, updating the amino acid requirements related to such animals is increasingly important.

Influence of Blood Group and Secretor Status on Carbohydrate Structures in Human Gastric Mucins: Implications for Peptic Ulcer

1995 ◽  
Vol 89 (4) ◽  
pp. 405-415 ◽  
Author(s):  
R. L. Sidebotham ◽  
J. H. Baron ◽  
J. Schrager ◽  
J. Spencer ◽  
J. R. Clamp ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Amino Acid ◽  
Blood Group ◽  
Average Length ◽  
Amino Acid Residues ◽  
Secretor Status ◽  
Increased Risk ◽  
The Mean ◽  
The Difference ◽  
Carbohydrate Chains

1. The content and distribution of carbohydrate was examined in mucus glycopolypeptides from human antral mucosae. 2. The mean amount of carbohydrate per 1000 amino acid residues was found to be similar in glycopolypeptides with A, B or H activity. It was slightly, though significantly, less in glycopolypeptides lacking these determinants, because carbohydrate chains were of a shorter average length than in the A-, B- or H-active preparations. This difference was reflected in the sizes of oligosaccharide—alcohols released from representative glycopolypeptides with alkaline borohydride. 3. Differences between A-, B- or H-active and non-secretor glycopolypeptides in terms of the mean number of carbohydrate chains per 1000 amino acid residues were found to be small, and without significance. 4. The average number of peripheral monosaccharide units per 1000 amino acid residues was greater in A-active than in H-active, and least in non-secretor, glycopolypeptides. This order was reversed for monosaccharide units incorporated into skeletal (core plus backbone) structures. The difference in each case was statistically significant. 5. These findings suggest that the increased risk of peptic ulcer associated with blood group O and non-secretor status is unlikely to be attributable to an inherent deficiency in the protective mucus layer, linked to differences between mucins that are associated with A, B or H activity. Other hypotheses linked to infection with Helicobacter pylori are examined.

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