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Biomedical subjects

P B Pencharz

Publications and source records attributed to P B Pencharz.

At least 19 recordsLinked to original sources
PubMed2005

Estimate of the variability of the lysine requirement of growing pigs using the indicator amino acid oxidation technique.

Although AA requirements for the mean in a population of growing pigs are well established, there are no direct estimates of their variability within the population. The indicator AA oxidation method allows repeated measurements in a short period of time so that the AA requirement can be determined for individual pigs. The objective was to determine the Lys requirement in individual pigs to derive a first estimate of the population mean requirement and its variability. Nine individually housed barrows (15 to 18 kg) were surgically implanted with venous catheters for isotope infusion. Pigs were offered, in random order, isonitrogenous and isoenergetic diets with one of seven Lys concentrations (4.8 to 15.5 g of Lys/kg diet, as-fed basis). The pigs were fed twice daily, except for study days when they received one-half of the daily allowance in eight equal hourly meals. After a validated minimum adaptation period, indicator (Phe) oxidation was determined for each dietary Lys level during a 4-h primed, constant infusion of L-[1-(14C)]Phe at a rate of 464 kBq/h. The Lys requirement was calculated using a two-phase linear regression crossover analysis within individual pigs. For each pig, Phe oxidation decreased linearly (P < 0.02) as the dietary Lys concentration increased until the requirement was reached; thereafter, Phe oxidation was not different. The true ileal digestible Lys requirement ranged from 7.5 to 10.6 g/kg of diet (as-fed basis) for the nine animals. The mean requirement for all pigs was 9.1 g/d (CV, 11.6%) or 93.9% (CV, 9.8%) of the predicted (NRC, 1998) requirement based on each pig's mean BW and energy intake. The measured and predicted requirements did not differ. The indicator AA oxidation method gave values for Lys requirement similar to conventional methods. The short (< 3 wk) experimental period allows, for the first time, the estimate of population variability, which provides for more accurate calculation of the effect of altering Lys intake on herd performance and production economics. This method is suitable to use with all dietary indispensable AA.

Animal Feed↗
PubMed2003

A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in healthy women.

Altered use of different dietary fatty acids may contribute to several chronic diseases, including obesity, noninsulin-dependent diabetes mellitus, and cardiovascular disease. However, few comparative data are available to support this link, so the goal of the present study was to compare the metabolism of [(13)C]oleate, [(13)C]alpha-linolenate, [(13)C]elaidate, and [(13)C]linoleate through oxidation and incorporation into plasma lipid fractions and adipose tissue. Each tracer was given as a single oral bolus to six healthy women. Samples were collected over 8 days, and (13)C was analyzed using isotope ratio mass spectrometry. At 9 h postdose, cumulative oxidation was similar for [(13)C]elaidate, [(13)C]oleate, and [(13)C]alpha-linolenate (19 +/- 1%, 20 +/- 4%, and 19 +/- 3% dose, respectively). Significantly lower oxidation of [(13)C]linoleate (12 +/- 4% dose; P < 0.05) was accompanied by its higher incorporation into plasma phospholipids and cholesteryl esters. Abdominal adipose tissue was enriched with [(13)C]alpha-linolenate, [(13)C]elaidate, or [(13)C]linoleate within 6 h. The percentage linoleate in plasma phospholipids correlated positively with [(13)C]linoleate and [(13)C]elaidate oxidation, indicating a potential role of background diet. Conversion of [(13)C]linoleate and [(13)C]alpha-linolenate to longer chain polyunsaturates was a quantitatively minor route of utilization.

Adipose Tissue↗
PubMed2001

Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Adolescent↗
PubMed2001

Is resting metabolic rate different between men and women?

A low resting metabolic rate (RMR) has been proposed as a possible cause for the increased body fat commonly seen in women compared with men. Absolute RMR is higher in men, but whether RMR adjusted for lean body mass (LBM) remains higher is unresolved. The objective of the present study was to determine whether RMR adjusted for various body composition factors differed between healthy adult men and women. Thirty men years, BMI and twenty-eight women years, BMI were included in the analyses. RMR was measured by open-circuit indirect calorimetry for 60 min. Extracellular water (ECW) was measured by corrected Br(-) space and total body water (TBW) by 2H dilution. LBM was estimated as TBW/0.732. Intracellular water (ICW) was calculated as TBW-ECW, and body cell mass (BCM) as ICW/0.732. Men were heavier and had higher BMI, LBM, BCM and ECW, but less fat mass. Absolute RMR was higher in men than women v. P<0.0001). This difference became non-significant when RMR was adjusted for LBM by ANCOVA v. P=0.2191), but remained significant when adjusted for BCM v. P=0.0249). Fat mass explained a significant amount of variation in RMR in women (r(2) 0.28, P=0.0038), but not in men (r(2) 0.03, P=0.3301). The relationships between body fat and the various subcompartments of BCM and RMR require further elucidation.

Adipose Tissue↗
PubMed2001

Tyrosine requirement of healthy men receiving a fixed phenylalanine intake determined by using indicator amino acid oxidation.

BACKGROUND: The currently accepted total aromatic amino acid requirement for adults is based on nitrogen balance measurements in individuals who received their intake of aromatic amino acids solely as phenylalanine. OBJECTIVE: The objective of this study was to determine the requirement for the amino acid tyrosine in healthy men receiving an adequate, but not excessive, intake of phenylalanine (9 mg x kg(-1) x d(-1)). DESIGN: The effect of a graded intake of tyrosine was determined in 6 healthy men consuming energy-sufficient diets containing 1 g protein x kg(-1) x d(-1). The tyrosine requirement was determined by using indicator amino acid oxidation methodology with L-[1-13C]lysine as the indicator. Subjects were studied at each of 7 tyrosine intakes. RESULTS: A graded intake of tyrosine had no effect on lysine flux. The mean tyrosine requirement was determined from the response of the oxidation of L-[1-13C]lysine to breath 13CO2. A 2-phase linear regression crossover analysis of breath 13CO2 identified the breakpoint and upper 95% confidence limit, which represents the mean and safe intakes, to be 6.0 and 7.0 mg x kg(-1) x d(-1), respectively. CONCLUSIONS: The safe intake of total aromatic amino acids calculated from the present results for tyrosine and our previous estimate for phenylalanine is estimated to be 21 mg x kg(-1) x d(-1). This intake is 1.5 times the currently recommended total aromatic amino acid intake of the FAO/WHO/UNU (1985), 14 mg x kg(-1) x d(-1). Furthermore, the absolute aromatic amino acid requirement may be dependent on the proportional balance of these amino acids in the diet.

Adult↗
PubMed2001

Total sulfur amino acid requirement in young men as determined by indicator amino acid oxidation with L-[1-13C]phenylalanine.

BACKGROUND: Determining the sulfur amino acid (SAA) requirements of humans has remained elusive because of the complex nature of SAA metabolism. Current recommendations are based on nitrogen balance studies. OBJECTIVE: The goal of the present study was to determine the methionine requirement of men fed a diet devoid of cysteine (total SAA requirement). DESIGN: Six men were randomly assigned to receive 6 graded intakes of methionine: 0, 6.5, 13.0, 19.5, 26.0, and 32.0 mg x kg(-1) x d(-1). The total SAA requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 (F(13)CO2)). The mean total SAA requirement was estimated with use of a linear regression crossover analysis, which identified a breakpoint of the F(13)CO2 response to methionine intake. RESULTS: On the basis of the mean measures of F(13)CO2, the mean requirement and population-safe intake (upper limit of the 95% CI) of total SAAs were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively. CONCLUSION: Although the mean SAA requirement is consistent with current guidelines for the total SAA intake, the population-safe intake is substantially higher than the currently recommended total SAA intake.

Adult↗
PubMed2001

Dietary cysteine reduces the methionine requirement in men.

BACKGROUND: Despite early evidence suggesting that dietary cysteine has a sparing effect on methionine requirements, some recent reports question the existence of a measurable sparing capacity. OBJECTIVE: The goal of the present study was to determine whether dietary cysteine could reduce the requirement for methionine in men consuming diets with and without cysteine. DESIGN: Six men were randomly assigned to receive graded intakes of methionine while fed a diet containing either no exogenous cysteine or an excess of cysteine (21 mg x kg(-1) x d(-1)). The methionine requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 and estimated by using a linear regression crossover analysis. RESULTS: The mean and population-safe (upper limit of the 95% CI) methionine requirements in the absence of exogenous cysteine were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively. The mean and population-safe methionine requirements in the presence of excess dietary cysteine were found to be 4.5 and 10.1 mg x kg(-1) x d(-1), respectively, representing a cysteine sparing effect of 64% in a comparison of mean methionine requirements and of 52% in a comparison of population-safe methionine intakes. Furthermore, the difference between population-safe intakes with and without dietary cysteine establishes a safe cysteine intake of 10.9 mg x kg(-1) x d(-1) in the presence of adequate methionine intakes. CONCLUSION: Our data suggest that dietary cysteine can reduce the exogenous requirement for methionine in men. These results strongly support the existence of a cysteine sparing effect in humans.

Adult↗
PubMed2001

The effect of graded intake of glycyl-L-tyrosine on phenylalanine and tyrosine metabolism in parenterally fed neonates with an estimation of tyrosine requirement.

Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 +/- 38 kJ. kg(-1).d(-1)) and protein (2.4 +/- 0.4 g.kg(-1).d(-1)) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-(13)C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO(2) (F(13)CO(2)) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg.kg(-1). d(-1) and 94 mg.kg(-1).d(-1), respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate.

Amino Acids↗
PubMed2000

Effect of tyrosine intake on the rate of phenylalanine hydroxylation in adult males.

This study evaluated the effect of varying levels of tyrosine intake on the estimation of phenylalanine hydroxylation. Healthy men were fed 1 g protein kg(-1) x d(-1) for a 2-day period. On the third day, subjects consumed a formula diet containing 1 g protein kg(-1) x d(-1) hourly over 10 hours, and primed hourly oral doses of L-[15N]phenylalanine and L-[3,3-2H2]tyrosine for the last 6 hours. Each subject was studied at 7 levels of tyrosine intake (3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12.0 mg x kg(-1) x d(-1)) at a constant intake of phenylalanine (9 mg x kg(-1) x d(-1), 4.55 micromol x kg(-1) x h(-1)). Phenylalanine hydroxylation was estimated from the ratio of plasma amino acid isotope enrichment of [15N]phenylalanine and [15N]tyrosine and the tyrosine flux estimated from [2H2]tyrosine enrichment. Phenylalanine and tyrosine fluxes showed no significant response to alterations in the intake of tyrosine. Linear regression analysis showed a significant response such that the rate of phenylalanine hydroxylation decreased as tyrosine intake increased (R2 = .21; P = .003). The mean rates of phenylalanine hydroxylation were 3.89 to 8.06 micromol x kg(-1) x h(-1). Given model uncertainties, the apparent protein breakdown observed at tyrosine intake levels less than 10.5 mg x kg(-1) x d(-1), and the significant differences observed between the present data and our prior data, we cannot estimate the tyrosine requirement with any degree of certainty with the present hydroxylation results.

Adult↗
PubMed2000

Pathogenesis of malnutrition in cystic fibrosis, and its treatment.

PATHOGENESIS: We have developed a model of the pathogenesis of malnutrition in cystic fibrosis. It consists of the relationship between nutrient balance and nutrient requirement. The validation has been conducted with respect to energy, but the same general principals can be applied to any nutrient. A patient with CF either loses weight or fails to grow normally if their absorbed energy intake is less than their total daily energy expenditure. Multiple factors have the potential to contribute to reduced energy intake including, anorexia, gastroeosophageal (GE) reflux leading to vomiting and hence food loss, as well as maldigestion. Another more recently recognized source of energy loss, is glucosuria as a result of CF related diabetes (CFRD). Conversely, lung inflammation appears to be related to increases in resting metabolic rate (RMR). Acute exacerbations of the chronic lung disease increases RMR which returns to a basal level some weeks after the inflammation is treated. In clinically stable patients with CF, RMR rises in a quadratic fashion as lung function falls. When FEV(1)is >85% predicted RMR is not different from controls, but it rises in a curvilinear fashion as FEV(1)falls. Initially it appears that patients adapt to their increased RMR by reducing their activity so their total daily energy expenditure (TDEE) is often no higher than controls. But this is by no means always the case. Furthermore good lung care requires CF patients to be involved in aerobic activities, hence their TDEE would rise. Although there has been considerable interest as to whether the genetic defect has an energy wasting effect, it appears genetic factors have little or no effect on RMR. TREATMENT: This starts with making an energy diagnosis. First, a 3 day faecal fat balance study is conducted. This provides information with regard to intake as well as to maldigestion. In addition a history of GE reflux is sought, since it can readily be treated with H(2)-blockers. If significant fat malabsorption exists, efforts are made to improve pancreatic enzyme dose and function. The possibility of CFRD also needs to be considered. We measure the RMR of the patient using open circuit indirect calorimetry. Recommendations for diet therapy are based on estimated TDEE, which is determined from RMR taking into account faecal losses. Diet therapy places the emphasis on increasing the fat content of the diet. We have conducted a study to determine whether or not oral supplements help increase TDEE and they did not; they merely replaced food energy. Conversely, nocturnal gastrostomy supplemental feeding, while reducing voluntary food energy intake by about 20%, does result in a significant increase in total daily energy intake. Our target is to achieve a completely normal nutritional status. Long term follow-up of these patients has shown significantly better survival in patients who achieve normal nutritional status. The advent of lung transplantation has added another dimension. In our experience, following a successful lung transplant, most patients no longer need their supplemental gastrostomy feeding. SUMMARY: Our clinic policy is to encourage a high fat diet (35-40% total energy) and our patients grow normally in height and weight until their lung disease deteriorates significantly. Patients who develop a negative energy balance seldom if ever respond to diet therapy and hence are candidates for supplemental nocturnal gastrostomy feeds. Gastrostomy fed patients constitute 3 to 5% of our total CF population of approximately 590 patients.

Basal Metabolism↗
PubMed2000

Challenges in the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic Fibrosis↗
PubMed2000

Threonine requirement of young men determined by indicator amino acid oxidation with use of L-[1-(13)C]phenylalanine.

BACKGROUND: Threonine is an indispensable amino acid with a complex degradative pathway. Use of the indicator amino acid oxidation technique should provide an estimate of the threonine requirement that is not affected by its metabolic pathway. OBJECTIVE: Our objective was to determine the requirement for threonine in men by using the indicator amino acid oxidation method and to provide statistical estimates of the population mean and 95% CIs of the threonine requirement. We hypothesized that the current World Health Organization estimate of the threonine requirement, 7 mg*kg(-)(1)*d(-)(1) (based on nitrogen balance studies), is too low. DESIGN: Six healthy men each received 6 different threonine intakes while consuming an energy-sufficient diet with 1.0 g L-amino acid mixture*kg(-)(1)*d(-)(1). The effect of graded alterations in dietary threonine intake on phenylalanine flux and oxidation was studied by using L-[1-(13)C]phenylalanine as the indicator amino acid. RESULTS: The results of two-phase linear regression crossover analysis showed that the mean threonine requirement, based on indicator oxidation, was 19.0 mg*kg(-)(1)*d(-)(1) with an upper safe intake of 26.2 mg*kg(-)(1)*d(-)(1). CONCLUSIONS: This is the first application of the indicator amino acid oxidation technique in humans to study the requirement for an indispensable amino acid with a complex degradative pathway. We found that the upper safe intake for 95% of the population is almost 4-fold higher than the current World Health Organization estimate.

Adult↗
PubMed2000

Distribution of protein turnover changes with age in humans as assessed by whole-body magnetic resonance image analysis to quantify tissue volumes.

We tested the hypothesis that nonmuscle lean tissue mass and its rate of protein catabolism remain constant with aging despite changes in the proportional contribution of these tissues to whole-body protein metabolism. Whole-body protein kinetics, using the 60-h oral [(15) N]glycine method, and muscle and nonmuscle protein catabolism, based on protein kinetic data, urinary N(tau)-methylhistine excretion and lean tissue volumes defined by whole-body magnetic resonance imaging, from eight healthy elderly subjects (5 females and 3 males, mean age 71.5 y) were compared with those of seven young persons (3 females and 4 males, mean age 28 y). There were no significant age or gender effects on rates of protein kinetics per L total lean tissue. There was a lower (P < 0.004) rate of muscle protein catabolism in the elderly (1.8 +/- 0.2 vs. 2.6 +/- 0.1 g. L(-1). d(-1)) and a trend (P = 0.08) for lower muscle volume (19.7 +/- 1.5 vs. 25.0 +/- 2.4 L). This contrasted with intraabdominal lean tissue, where the rate of protein catabolism (13. 8 +/- 0.6 vs. 13.2 +/- 0.9 g. L(-1 ). d(-1)) and volume (7.5 +/- 0.3 vs 8.0 +/- 0.5 L) did not differ between age groups. Thus, the decrease in the contribution by muscle to whole-body protein metabolism with age is associated with an increase from 62 to 74% (P < 0.001) in the contribution by nonmuscle lean tissues. These findings have potential implications for the nutrition of both normal and sick elderly persons.

Aged↗
PubMed2000

Organ and plasma amino acid concentrations are profoundly different in piglets fed identical diets via gastric, central venous or portal venous routes.

In a previous study in piglets fed identical diets intravenously, intraportally or intragastrically, we determined that small intestinal atrophy affects nitrogen metabolism to a greater extent than liver by-pass. Because whole-body amino acid homeostasis is dependent on interorgan metabolism, we also measured the free amino acid concentrations in liver, small intestinal mucosa and kidney in order to study alterations in amino acid metabolism within these organs. Piglets (n = 15; 2-4 d old) were fed identical diets continuously for 8 d via gastric (IG), portal (IP) or central venous (IV) catheters. Concentrations of all measured amino acids were affected by route of feeding in one or more organs. In particular, urea cycle amino acid concentrations were altered in plasma and mucosa of IV and IP pigs, suggesting that arginine synthesis by an atrophied gut may have been limited. Furthermore, most indispensable amino acid concentrations were lower in IP pigs for all organs vs. IG pigs; however, except for phenylalanine, plasma concentrations of these amino acids were not different, demonstrating the liver's "smoothing" capability. Gut atrophy in both IV and IP pigs resulted in significantly lower concentrations of all indispensable amino acids compared with IG pigs. Alterations of all amino acids in various organs due to route of feeding suggest that more detailed analyses of regulatory mechanisms and amino acid interactions on interorgan amino acid metabolism are necessary for all amino acids.

Amino Acids↗
PubMed2000

Current total parenteral nutrition solutions for the neonate are inadequate.

The amino acid requirements of the parenterally fed neonate are poorly defined. Newborn infants are at risk for amino acid deficiency and toxicity, due to lack of small intestinal metabolism and metabolic immaturity. We discuss recent evidence that identifies inadequacies of commercial amino acid solutions with respect to the balance and quantity of aromatic amino acids, and sulphur amino acids. We present data demonstrating that impaired small intestinal metabolism (or lack of first pass metabolism) alters the whole body requirement for methionine, threonine, and arginine, and discuss the potential adverse effects of excess or inadequate parenteral amino acid intake.

Amino Acids↗
PubMed2000

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

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 approximately 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 (13)CO(2) in breath (F(13)CO(2)) under dietary conditions of adequate energy, protein (1.5 g x kg(-1) x day(-1)), and phenylalanine (25 mg x kg(-1) x day(-1)). Lysine oxidation and F(13)CO(2) were determined using a primed 4-h oral equal-dose infusion of L-[1-(13)C]lysine. Lysine oxidation and F(13)CO(2) 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 x kg(-1) x day(-1), respectively). At Tyr intakes of >16.3 and 19.2 mg x kg(-1) x day(-1), lysine oxidation and F(13)CO(2), 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 approximately 5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.

Breath Tests↗
PubMed2000

Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans.

The threonine dehydrogenase (TDG) pathway is a significant route of threonine degradation, yielding glycine in experimental animals, but has not been accurately quantitated in humans. Therefore, the effect of a large excess of dietary threonine, given either as free amino acid (+Thr) or as a constituent of protein (+P-Thr), on threonine catabolism to CO(2) and to glycine was studied in six healthy adult males using a 4-h constant infusion of L-[1-(13)C]threonine and [(15)N]glycine. Gas chromatography-combustion isotope ratio mass spectrometry was used to determine [(13)C]glycine produced from labeled threonine. Threonine intakes were higher on +Thr and +P-Thr diets compared with control (126, 126, and 50 micromol x kg(-1) x h(-1), SD 8, P < 0.0001). Threonine oxidation to CO(2) increased threefold in subjects on +Thr and +P-Thr vs. control (49, 45, and 15 micromol x kg(-1) x h(-1), SD 6, P < 0.0001). Threonine conversion to glycine tended to be higher on +Thr and +P-Thr vs. control (3.5, 3.4, and 1.6 micromol x kg(-1) x h(-1), SD 1.3, P = 0.06). The TDG pathway accounted for only 7-11% of total threonine catabolism and therefore is a minor pathway in the human adult.

Adult↗