Amino acids, glutamine, and protein metabolism in very low birth weight infants

Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5-(15)N]glutamine, [2H5]phenylalanine, [1-(13)C,15N]leucine, and [15N2]urea tracers. An acute increase in parenteral amino acid infusion for 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis.     

Effect of two amino acid solutions on leucine turnover in preterm infants

OBJECTIVE: To assess the effect of two different parenteral amino acid mixtures, Trophamine and Primene, on leucine turnover in preterm infants. METHOD: Leucine kinetics were measured with [5,5,5 D3]leucine tracer in 15 infants receiving Trophamine (group 'T') (mean birth weight 1,263 g) and 22 who received Primene (group 'P') (mean birth weight 1,336 g) during two study periods, within a few hours after birth but before introduction of parenteral amino acid solution, and again at postnatal day 7. The rate of appearance of leucine was calculated from the enrichment of alpha-ketoisocaproic acid in plasma. RESULTS: There were no significant differences in leucine turnover within a few hours after birth in the two groups. In the infants who received Primene leucine turnover on day 7 was significantly lower than in those who received Trophamine (269 +/- 43 vs. 335 +/- 27, p < 0.05). Despite a higher intake of leucine in the Trophamine group (108 +/- 10 vs. 77 +/- 8 micromol.kg(-1).h(-1)), leucine released from proteins at day 7 was higher in this group compared to Primene (227 +/- 27 vs. 192 +/- 42 micromol.kg(-1).h(-1)). CONCLUSIONS: Primene administration results in lower leucine released from proteins, an estimate of protein breakdown, than Trophamine in preterm infants. Increases in whole body leucine turnover in response to administration of i.v. amino acids is influenced by the composition of the amino acid mixture. The factors responsible for this difference remain to be elucidated.     

Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study.

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Whole body protein metabolism in children with cancer.

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

15N tracer kinetic studies on the validity of various 15N tracer substances for determining whole-body protein parameters in very small preterm infants

Reliable 15N tracer substances for tracer kinetic determination of whole-body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post-conceptual age was 32.2 +/- 0.8 weeks, and their body weight was 1670 +/- 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]glycine (Ib). In a second group of three infants with a post conceptual age of 15N-labeled 32.0 +/- 1.0 weeks and a body weight of 1,907 +/- 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three-pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 +/- 3.1 g kg-1 d-1 (Ia), 16.2 +/- 2.5 g kg-1 d-1 (Ib), and 10.8 +/- 3.0 g kg-1 d-1 (II). We were able to demonstrate an overestimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N-labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole-body protein parameters in very small preterm infants.     

Whole body protein turnover and urea production of preterm small for gestational age infants fed fortified human milk or preterm formula

OBJECTIVES: To investigate protein metabolism and urea production in preterm small for gestational age neonates fed a preterm formula or fortified human milk. METHODS: Ten preterm small for gestational age neonates were fed either their own mother's milk fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was 24% higher in the preterm formula group than in the fortified human milk group. No differences in protein turnover, synthesis and breakdown were observed between the two groups, but protein accretion was 71% to 79% higher in the preterm formula group than the fortified human milk group. Urea production rates were not different in the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified human milk appear equally well tolerated by preterm small for gestational age neonates, but protein accretion was higher in the preterm formula group. In preterm small for gestational age infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.     

Protein turnover rates in sick, premature neonates during the first few days of life.

Rates of protein turnover were measured in 19 infants during the first few days of life while they were receiving i.v. glucose. The technique consisted of a continuous i.v. infusion of L-[1-13C]leucine to measure whole body leucine flux and determination of total urinary nitrogen excretion to assess leucine oxidation rates. Subsequent to each of the studies, the decision to start total parenteral nutrition (TPN) was made by the clinician concerned, with the result that seven infants did not start TPN and 12 did. There were significantly greater urinary nitrogen excretion (p less than 0.001) and lower rates of whole body protein synthesis (p = 0.024) and breakdown (p = 0.015) in those who did start TPN compared with those who did not. The marked difference in nitrogen excretion between the two groups suggests that this could be a useful determinant for deciding which neonate should start TPN.     

Whole-body protein parameters in premature infants: a comparison of different 15N tracer substances and different methods.

[15N]glycine, [15N]leucine, and [15N]yeast protein thermitase hydrolysate (YPTH) as tracers for investigating the protein turnover rates in premature infants were studied in nine human milk-fed neonates (born after 32 to 34 wk of gestation) by paired comparison of the tracers. The 15N enrichment of total urinary nitrogen and ammonia after administration of a single oral dose of 15N was measured by emission spectrometry. Flux rates were calculated using a three-compartment model and the ammonia end product method. The mean whole-body protein synthesis rates, as determined by the three-compartment model derived from the three 15N tracers, differed significantly (p less than 0.01) among [15N]glycine (15.9 g/kg/d), [15N] leucine (9.1 g/kg/d), and 15N-YPTH (5.9 g/kg/d). When the corresponding rates were determined from the excretion of label in ammonia, the results showed the opposite tendency; the lowest apparent synthesis rates were found after [15N]glycine (7.5 g/kg/d), followed by [15N]leucine (14.4 g/kg/d), and the highest figure resulted after [15N] YPTH (16.7 g/kg/d). The results of this comparison substantiate the assumption that there are methodologic errors in connection with the use of different tracers and models for the calculation of whole-body protein parameters in preterm infants, with respect to the main requirement for tracer kinetic studies; the tracer nitrogen must be representative of total amino acid nitrogen. Seen in this light, mixtures of completely labeled amino acids such as YPTH may represent the most reliable tracer substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Corticosteroids increase protein breakdown and loss in newly diagnosed pediatric Crohn disease

Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-α therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-(13)C] leucine, and [(15)N(2)] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition.     

Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome

Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole body protein turnover measured with 13C-leucine and energy expenditure in preterm infants

Our study was undertaken in preterm infants to examine the relationship of whole body protein kinetics with protein intake and energy expenditure. Leucine kinetics were determined in seven low birth wt preterm infants fed human milk or human milk enriched with protein (2.5 to 4.3 g protein/kg.d). The infants received a short (4-h) constant infusion of L-[1-13C]leucine and leucine turnover and oxidation were calculated from 13C-plasma leucine and expired 13CO2 enrichments measured by mass spectrometry. Energy expenditure was measured by indirect calorimetry. Nonoxidative leucine disposal (an estimate of protein synthesis) and leucine derived from protein (an estimate of protein breakdown) were, respectively, 2.98 +/- 0.82 and 2.06 +/- 0.74 mumol/kg.min. Whole body protein turnover and deposition, derived from leucine kinetics, were 8.22 +/- 2.31 and 2.17 +/- 0.50 g/kg.d, whereas energy expenditure was 56.3 kcal/kg.day. Protein turnover was correlated with protein intake but not with protein deposition. Energy expenditure was correlated with protein turnover, synthesis, and breakdown but not with protein deposition. These data are in agreement with the fact that protein deposition depends upon protein intake, but they also suggest that an elevated protein deposition is not necessarily the result of a rapid protein turnover or associated with an elevated energy expenditure.     

Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover, we studied the leucine turnover in preterm infants soon after birth and again after 7 days. Ten infants from preeclamptic mothers (birth weight 1,280 +/- 240 g, gestational age 31 +/- 2 weeks) and 15 control patients (birth weight 1,320 +/- 210 g, gestational age 30 +/- 2 weeks) were enrolled. The leucine turnover was measured using a primed constant 5-hour intravenous infusion of [1-(13)C]leucine within the first 24 h after delivery and again on day 7 of life. The turnover (leucine flux; micromol.kg(-1).h(-1)) was calculated from the enrichment in alpha-ketoisocaproic acid in plasma. The leucine turnover on day 1 was 300 +/- 65 in the preeclampsia group and 358 +/- 70 in the controls (ANOVA, p < 0.05). The values on day 7 were 474 +/- 73 in the preeclampsia group and 485 +/- 80 in the control group (n.s.). To conclude, the leucine turnover on day 1 is lower in infants of preeclamptic mothers as compared with controls. This difference has disappeared on day 7 of life after receiving the same protein and energy intake.     

Urea utilization by the intestinal flora, of infants fed mother's milk and a formula diet, as measured with the 15N-tracer technique

15N-Incorporation by intestinal bacteria was measured under different feeding conditions in 16 infants after a single oral loading of 165 mg [15N2]urea X kg-1 body weight as a tracer. In five subjects on a mother's milk diet, the 15N-excess in the isolated intestinal bacteria was 1.08 (0.17-1.85) atom-%. The mean 15N-excess in the intestinal flora of five formula-fed subjects did not differ significantly from these values [0.63 (0.17-1.05) atom-%]. A trend to a higher incorporation of 15N from labeled urea by the intestinal flora was seen in four infants, who were adapted to an increased nutritional urea supply on a special formula, containing 14 g of milk protein, 80 g lactose, 36 g fat, and 0.35 g urea X L-1. The same observation was made in two infants with chronic renal failure. The incorporation of urea nitrogen by the putrefactive intestinal flora of infants on a formula diet as well as by the bifidobacterial flora of those on mother's milk feeding indicates the utilization of ureas as a source of bacterial protein and nucleic acid synthesis. The adaptive usage of urea for the bacterial metabolism can be considered as a sign of supportive detoxification by the intestinal flora.     

Minimum protein intake for the preterm neonate determined by protein and amino acid kinetics

Lower limits of protein needs in prematurely born neonates have not been adequately studied, yet providing protein in amounts maximizing accretion without excess is a goal in these infants' nutritional care. We hypothesized that with the use of amino acid oxidation methodology, it would be possible to define minimum protein requirement. Our objective was to investigate protein kinetics during short-term changes in protein intake by measurement of nitrogen balance and amino acid flux and oxidation using [(15)N]glycine, [(13)C]phenylalanine, and [(13)C]leucine tracers. Protein kinetics were examined in 21 preterm infants (gestational age: 29 +/- 3 wk; birth weight: 1091 +/- 324 g) at five protein intakes (1.0, 1.5, 2.0, 2.5, and 3.0 g x kg(-1) x d(-1)) with 1 d of adaptation to the test intakes. From nitrogen balance data, a protein need of 0.74 g x kg(-1 x -1) was estimated to achieve zero balance. For all three amino acids, flux and oxidation estimates were not different across protein intakes. Whole-body protein synthesis and breakdown estimates from [(15)N]ammonia data were 14.6 +/- 3.4 and 14.4 +/- 4.1 g x kg(-1) x d(-1), respectively. Glycine flux (680 +/- 168 micromol x kg(-1) x h(-1)) was greater than leucine flux (323 +/- 115 micromol x kg(-1) x h(-1)), which was greater than phenylalanine flux (84.3 +/- 35.2 micromol x kg(-1) x h(-1)). Leucine oxidation (36.7 +/- 15.6 micromol x kg(-1) x h(-1)) was also greater than phenylalanine oxidation (6.64 +/- 4.41 micromol x kg(-1) x h(-1)). Infants in our study were able to adapt to short-term changes in protein intake with little consequence to the overall whole-body protein economy, as measured by the three test amino acids.     

Metabolism of methionine in the newborn infant: response to the parenteral and enteral administration of nutrients

The rates of transmethylation and transsulfuration of methionine were quantified using [1-(13)C]methionine and [C2H3]methionine tracers in newborn infants born at term gestation and in prematurely born low birth weight infants. Whole body rate of protein breakdown was also measured using [2H5]phenylalanine. The response to enteral formula feeding and parenteral nutrition was examined in full term and prematurely born babies, respectively. The relative rates of appearance of methionine and phenylalanine were comparable to the amino acid composition of mixed body proteins. Rates of transmethylation were high, both in full term infants (fast 32 +/- 14 micromol kg(-1) x h(-1); fed 21.7 +/- 3.2) and in preterm infants (57.2 +/- 14.8). Significant flux through the transsulfuration pathway was evident (full term: fast 6.0 +/- 4.4, fed 4.1 +/- 2.1; preterm: 24.9 +/- 9.9 micromol kg(-1) x h(-1)). Transsulfuration of methionine is evident in the human newborn in the immediate neonatal period, suggesting that cysteine may not be considered a "conditionally" essential amino acid for the neonate. The high rate of transmethylation may reflect the high methylation demand, whereas high rates of transsulfuration in premature babies may be related to high demands for glutathione and to the amounts of methionine in parenteral amino acid mixtures.     

Changes in protein turnover after the introduction of parenteral nutrition in premature infants: comparison of breast milk and egg protein-based amino acid solutions.

Rates of protein turnover were measured in 20 infants receiving either Vamin Infant (group A) or Vamin 9 glucose (group B) as the amino acid source in total parenteral nutrition. A constant infusion of L-[1-13C]leucine was used to measure whole body leucine flux, and leucine oxidation rates were derived from measurements of total urinary nitrogen excretion. Infants were first studied when receiving only i.v. glucose and again on each of the next 4 d as total parenteral nutrition was gradually increased to a maximum of 430 mg nitrogen/kg/d and 90 nonprotein kcal/kg/d. Net protein gain and protein synthesis and breakdown rates increased progressively for all infants taken together over the study period as i.v. nutrition was increasing (p less than 0.001). There were no differences between groups in the changes in net protein gain and rates of protein synthesis and breakdown throughout the study period. Nitrogen retention on d 5 for the two groups was similar (60 +/- 16% and 67 +/- 11% in groups A and B, respectively). In a subgroup of infants, measurements were repeated on d 8, when the intake had been constant for 3 d. Protein retention was the same as on d 5, but both synthesis and breakdown were increased. It is concluded that rates of protein turnover increase significantly in response to increasing i.v. nutrition and that this elevation was not influenced by the composition of the amino acid mixture given.     

15N tracer investigations of the physiological availability of urea nitrogen in mother's milk

The physiological availability of urea in mother's milk was investigated in tracer studies using [15N]2 urea and involving 22 infants. The incorporation of 15N into the body protein was established in 16 subjects by emission spectrophotometrical determination of the 15N excess in the serum protein. Between 2% and 3.6% of the serum protein is synthesized from the urea nitrogen in mother's milk. In further studies on the 15N balance in 6 infants, renal excretion of 15N after oral multiple and single impulse labelling with [15N]2 urea constituted 60% of the dose administered. Three-tenths-2.5% was excreted in the feces. The retention of 15N in the protein pool varied between 16.7 and 61.4%.     

Albumin synthesis in premature infants: determination of turnover with [15N]glycine

Albumin turnover was studied in seven small premature infants who received a constant infusion of [15N]glycine for 60-72 h. Gas chromatography-mass spectrometry was used to measure the rate of appearance of [15N]glycine in albumin isolated from the blood. By comparing the linear increment of [15N]glycine in blood albumin with plateau labelling of urinary [15N]hippurate, which was assumed to reflect intrahepatic isotopic abundance in [15N]glycine, the fractional synthetic rate for albumin was found to be 0.09-0.177 day-1 (mean +/- SD = 0.122 +/- 0.041 day-1). The absolute synthesis rate for albumin was 0.3 +/- 0.099 g/dl plasma X day-1 and the total plasma synthetic rate was 117.6 +/- 37.0 mg/kg X day-1. The glycine flux was 326.0-927.7 mumol/kg X h-1 (mean +/- SD 516.7 +/- 218.4 mumol/kg hr-1). The percentage of the glycine flux incorporated into albumin in the total vasculature was 0.425 +/- 0.344. The fractional synthetic rate and the absolute synthetic rate for albumin in these small premature infants are much higher than values obtained in healthy young adults studied with a similar methodology. The relatively low serum albumin concentrations typical of premature infants appear to be referable to more rapid turnover of a small plasma pool rather than a diminution in the rate of albumin synthesis.     

Amino acid metabolism in the human fetus at term: leucine, valine, and methionine kinetics

Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.