Glucose and pyruvate metabolism in severe chronic obstructive pulmonary disease.

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood but may involve alterations in macronutrient metabolism. Changes in muscle oxidative capacity and lactate production during exercise suggest glucose metabolism may be altered in COPD subjects. The objective of this study was to determine differences in the rates of glucose production and clearance, the rate of glycolysis (pyruvate production), and oxidative and nonoxidative pyruvate disposal in subjects with severe COPD compared with healthy controls. The in vivo rates of glucose production and clearance were measured in 14 stable outpatients with severe COPD (seven with low and seven with preserved body mass indexes) and 7 healthy controls using an intravenous infusion of [(2)H(2)]glucose. Additionally, pyruvate production and oxidative and non-oxidative pyruvate disposal were measured using intravenous infusions of [(13)C]bicarbonate and [(13)C]pyruvate. Endogenous glucose flux and glucose clearance were significantly faster in the combined COPD subjects (P = 0.002 and P < 0.001, respectively). This difference remained significant when COPD subjects were separated by body mass index. Pyruvate flux and oxidation were significantly higher in the combined COPD subjects than controls (P = 0.02 for both), but there was no difference in nonoxidative pyruvate disposal or plasma lactate concentrations between the two groups. In subjects with severe COPD, there are alterations in glucose metabolism leading to increased glucose production and faster glucose metabolism by glycolysis and oxidation compared with controls. However, no difference in glucose conversion to lactate via pyruvate reduction is observed.

Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease.

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Changes in protein metabolism and systemic inflammation may contribute to increased resting energy expenditure (REE) in COPD, leading to an energy imbalance and loss of fat and fat-free mass. The objective of this study was to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation. Resting energy expenditure was determined using indirect calorimetry in 14 stable outpatients with severe COPD (7 with low and 7 with preserved body mass indices) and 7 healthy controls. Endogenous leucine flux, leucine oxidation, and nonoxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis, were measured using intravenous infusions of (13)C-bicarbonate and 1-(13)C-leucine. Total body water, from which fat-free mass and fat mass were calculated, was determined using an intravenous bolus of deuterated water. Plasma markers of systemic inflammation were also measured. As a group, subjects with COPD had increased REE adjusted for fat-free mass (P < .001) and faster rates of endogenous leucine flux (P = .006) and nonoxidative leucine disposal (P = .002) compared with controls. There was a significant correlation between REE and both endogenous leucine flux (P = .02) and nonoxidative leucine disposal (P = .008). Plasma concentrations of the inflammatory markers C-reactive protein and interleukin-6 were not different between COPD subjects and controls. Increased rates of protein turnover are associated with increased REE and loss of fat-free mass in COPD.

Tyrosine requirement during the rapid catch-up growth phase of recovery from severe childhood undernutrition.

The requirement for aromatic amino acids during the rapid catch-up in weight phase of recovery from severe childhood undernutrition (SCU) is not clearly established. As a first step, the present study aimed to estimate the tyrosine requirement of children with SCU during the catch-up growth phase of nutritional rehabilitation using a diet enriched in energy and proteins. Tyrosine requirement was calculated from the rate of excretion of ¹³CO2 (F ¹³CO2) during [¹³C]phenylalanine infusion in thirteen children with SCU, five females and eight males, at about 19 d after admission when the subjects were considered to have entered their rapid catch-up growth phase and were consuming 627.3 kJ and about 3.5 g protein/kg per d. Measurements of F ¹³CO2 during [¹³C]phenylalanine infusion were made on two separate days with a 1 d interval. Three measurements at tyrosine intakes of 48, 71 and 95 mg/kg per d were performed on experimental day 1 and measurements at tyrosine intakes of 148, 195 and 241 mg/kg per d were performed on experimental day 2. An estimate of the mean requirement was derived by breakpoint analysis with a two-phase linear regression cross-over model. The breakpoint, which represents an estimate of the mean tyrosine requirement, is a value of 99 mg/kg per d when the children were growing at about 15 g/kg per d. The result indicates that the mean requirement for tyrosine during the catch-up growth phase of SCU is about 99 mg/kg per d under similar conditions to the present study.

Aromatic amino acid requirements in healthy human subjects.

Dietary aromatic amino acids are needed to meet the requirements for phenylalanine and tyrosine for protein synthesis. The amounts needed for neurotransmitter synthesis and other biological processes are small and quantitatively negligible. The earlier nitrogen balance-based estimates were judged to be inadequate. Very recently, there have been 3 estimates published based on the indicator amino acid oxidation technique, which average 42 mg.kg(-1).d(-1). This average value was obtained by feeding subjects a tyrosine-free diet and hence is an estimate of the mean maximum phenylalanine requirement. The mean minimum phenylalanine requirement estimate in the presence of an excess of tyrosine is 9.1 mg.kg(-1).d(-1). Hence, tyrosine can spare 78% of the dietary phenylalanine need. Finally the optimal proportions of dietary phenylalanine and tyrosine have been shown to be 60:40, respectively.

Evidence that phenylalanine may not provide the full needs for aromatic amino acids in children.

Phenylalanine is nutritionally classified as an indispensable amino acid and can be converted to tyrosine by phenylalanine hydroxylation. The initial goal of the present study was to determine the aromatic amino acid (phenylalanine plus tyrosine) requirements in healthy children fed a diet without tyrosine by using the indicator amino acid oxidation (IAAO) method using lysine as the indicator amino acid. Healthy school-age children (n = 5) were fed in random order a diet with eight graded intakes of phenylalanine without tyrosine. The requirement was determined by the rate of recovery of CO2 from L-[1-C]lysine oxidation (FCO2). Phenylalanine (total aromatic amino acid) requirement, in the absence of tyrosine, for children was determined to be 28 mg/kg/d, which was only 64% of the adult requirement, which is biologically absurd. A possible reason for the lower estimate of phenylalanine requirement could be lower phenylalanine hydroxylation rate in children, which is supported by the finding of lower urinary tyrosine/phenylalanine ratios in children compared with adults. In conclusion, this study indicates that phenylalanine may not provide the total needs for aromatic amino acids in children fed an amino acid-based diet without tyrosine.

Leucine is not a good choice as an indicator amino acid for determining amino acid requirements in men.

Leucine tracer has been widely used for examining whole-body protein turnover in humans, but has not been evaluated as an indicator to be used in the indicator amino acid oxidation (IAAO) method. The goal of this study was to determine whether the L-[1-(13C)]leucine isotope is an acceptable indicator by comparing it with an established tracer, L-[1-(13C)]lysine. Healthy men (n = 7; 29.9 +/- 4.8 y old) were fed in random order a diet with 7 graded intakes of phenylalanine without tyrosine. In the first study (n = 5), subjects were administered an excess leucine intake of 65 mg/(kg.d), and in the second study (n = 5), they were given the mean requirement of 45 mg/(kg.d) to determine whether leucine intake affected the pattern of response. Previous IAAO studies using lysine and phenylalanine demonstrated a clear pattern in 13CO2 production, i.e., increasing test amino acid intake resulted in a linear decrease to plateau, with a readily discernable breakpoint indicating the requirement. This pattern of production of 13CO2, indicates clear partitioning of the indicator amino acid between oxidation and protein synthesis. This was not observed with leucine at an intake of 65 mg/(kg.d). Conversely, at the lower leucine intake of 45 mg/(kg.d), a breakpoint was seen and a total aromatic amino acid requirement estimate that did not differ from that obtain using lysine as the indicator was obtained. In conclusion, leucine may be used as the indicator in the IAAO technique only when the daily intake leucine is given at its mean requirement level and the potential metabolic effects of other variables are taken into consideration.

Aromatic amino acid requirements in healthy men measured by indicator amino acid oxidation.

BACKGROUND: In the current literature, no agreement exists on estimates for aromatic amino acid (phenylalanine plus tyrosine) requirements as measured by stable-isotope techniques. OBJECTIVE: The goal of the present study was to determine the phenylalanine requirement in healthy men who were fed a diet without tyrosine by using the indicator amino acid oxidation method. DESIGN: Five healthy men were assigned to receive in random order diets devoid of tyrosine and with 8 graded intakes of phenylalanine (5, 10, 15, 25, 35, 45, 60, and 70 mg x kg(-1) x d(-1)). The phenylalanine requirement was measured by the rate of 13CO2 release (F13CO2) from L-[1-(13)C]lysine oxidation. RESULTS: The graded intakes of phenylalanine had no effect on lysine flux, as required for this method. The phenylalanine (ie, total aromatic amino acid) requirement, in the absence of tyrosine, was estimated to be 48 mg x kg(-1) x d(-1) by applying a two-phase linear regression crossover model to the F13CO2 data. CONCLUSIONS: In the absence of tyrosine, the mean phenylalanine requirement is higher than the current FAO/WHO/UNU (1985) and Dietary Reference Intake (2002) recommendations.