Total Amino Acid Intake Research Articles

Context-dependent impact of the dietary non-essential amino acid tyrosine on Drosophila physiology and longevity.

Dietary protein intake modulates growth, reproduction, and longevity by stimulating amino acid (AA)-sensing pathways. Essential AAs are often considered as limiting nutrients during protein scarcity, and the role of dietary non-essential AAs (NEAAs) is less explored. Although tyrosine has been reported to be crucial for sensing protein restriction in Drosophila larvae, its effect on adult physiology and longevity remains unclear. Here, using a synthetic diet, we perform a systematic investigation of the effect of single NEAA deprivation on nutrient-sensing pathways, reproductive ability, starvation resistance, feeding behavior, and life span in adult female flies. Specifically, dietary tyrosine deprivation decreases internal tyrosine levels and fecundity, influences AA-sensing machineries, and extends life span. These nutritional responses are not observed under higher total AA intake or in infertile female flies, suggesting a context-dependent influence of dietary tyrosine. Our findings highlight the unique role of tyrosine as a potentially limiting nutrient, underscoring its value for dietary interventions aimed at enhancing health span.

Reduced Na+ K+ -ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged ex vivo amino acid transporter activity.

Fetuses with intrauterine growth restriction (IUGR) have reduced muscle mass that persists postnatally, which may contribute to their increased risk for adult onset metabolic diseases, such as diabetes and obesity. Amino acid transporter-mediated histidine uptake and system L amino acid transporter activity were similar in sarcolemmal membranes isolated from control and IUGR hindlimb skeletal muscle. Activity of Na+ K+ -ATPase, which is responsible for establishing the sodium gradient necessary for system A and N amino acid transporter function, was significantly reduced in IUGR skeletal muscle sarcolemma compared to control. ATP content was lower in IUGR skeletal muscle. Expression and phosphorylation of proteins in the mechanistic target of rapamycin pathway were similar in control and IUGR skeletal muscle homogenate. Our data suggest that lower Na+ K+ -ATPase activity, which reduces the driving force for active amino acid transport, and lower ATP availability contribute to reduced amino acid uptake and protein synthesis in IUGR fetal skeletal muscle. Fetuses with intrauterine growth restriction (IUGR) have lower muscle mass that persists postnatally. Using a sheep model of placental insufficiency and IUGR, we have previously demonstrated lower net total uptake of amino acids by the fetal hindlimb and lower skeletal muscle protein synthesis rates. To investigate the mechanisms underlying these changes, we tested the hypothesis that ex vivo amino acid transporter and Na+ K+ -ATPase activity is reduced, and ex vivo ATP levels are lower in hindlimb skeletal muscle of the IUGR fetus. We developed a novel protocol to measure transporter-mediated histidine uptake, system L amino acid transporter activity and Na+ K+ -ATPase activity using sarcolemmal membranes isolated from hindlimb muscle of control (CON, n=11-12) and IUGR (n=12) late gestation fetal sheep. We also determined ATP content and the activity of insulin and mechanistic target of rapamycin (mTOR) signalling, which are involved in regulating cellular amino acid uptake and protein synthesis, by measuring the expression and phosphorylation of AKT, 4E-BP1, eIF2α, AMPKα, p70 S6 kinase and rpS6 in muscle homogenates. Transporter-mediated histidine uptake and system L activity were similar in control and IUGR sarcolemma, although ex vivo Na+ K+ -ATPase activity was lower by 64% (P=0.019) in IUGR sarcolemma. ATP content was lower by 25% (P=0.007) in IUGR muscle. Insulin, AMPK, and mTOR signalling activity was similar in control and IUGR muscle. We speculate that reduced muscle sarcolemmal Na+ K+ -ATPase activity and lower ATP content diminishes the sodium gradient in vivo, resulting in a reduced driving force for sodium-dependent transporters and subsequently lower muscle amino acid uptake.

The Uptake and Release of Amino Acids by Staphylococcus aureus at Mid-Exponential and Stationary Phases and Their Corresponding Responses to Changes in Temperature, pH and Osmolality.

Staphylococcus aureus is an important pathogen that is associated with nosocomial infections, as well as food poisoning. This bacterium is resistant to antimicrobial agents and can survive in a wide range of environmental conditions. The aim of this study was to measure the uptake and release of amino acids by S. aureus at mid-exponential and stationary phases of growth following exposure to a combination of conditions including variations in temperature, pH and NaCl. Bacterial cells were grown up to mid-exponential and stationary phases in tryptic soy broth (TSB), where the supernatants were collected for analyses of amino acids to determine the uptake and release characteristics. The uptake/release of amino acids was estimated by subtracting the initial levels of the free amino acids in the media from those measured at mid-exponential and stationary phases of growth. When cells were grown at ideal conditions, the analyses revealed that significant uptake of amino acids had occurred by stationary phase compared with the mid-exponential phase. A substantial release of valine and tyrosine into the external media was observed by cells at stationary phase. At both phases, the uptake and release patterns were significantly different between cells grown under ideal control conditions, when compared with those grown under various combinations of sub-optimal environmental conditions. The analyses of the supernatants harvested from controls and treatment groups at exponential phase indicated that the total uptake of amino acids was reduced approximately five times by cells grown with addition of 2.5% NaCl or with pH6 at 35°C, and 2-fold by cells grown at pH8 at 35°C. However, the final quantities of amino acids taken up by cells grown to stationary phase did not significantly alter between control and treated samples. Valine was found to be the most abundant amino acid that was significantly released into the media at stationary phase by both control and treated samples. It was evident that diverse environmental conditions resulted in differential patterns of amino acid uptake and release during adaptation to designated conditions.

Are Dietary Amino Acids or Protein Quality Associated with Infant Length Gain from 6 to 12 Months in Rural Malawi? (P10-010-19)

Objectives1) to estimate the probability of inadequate amino acid intake among infants 9–10 months of age in rural Malawi2) to evaluate whether dietary amino acid intake or protein quality are associated with length gain from 6 to 12 months of age MethodsWe assessed total amino acid intake from breast milk and complementary foods in 285 infants. Breast milk intake and complementary foods were estimated using dose-to-mother deuterium oxide dilution method and repeat 4-pass interactive 24-hour recall interviews, respectively. Amino acid composition values were taken from FAO human milk profile, Tanzania Food Composition table and International Minilist. Protein quality was estimated using Digestible Indispensable Amino Acid Score (DIAAS). Probability of intake below Estimated Average Requirement (EAR) for each amino acid was estimated using National Cancer Institute (NCI) method. We estimated protein quality of complementary food using median DIAAS. We assumed a DIAAS of ≥0.75 to represent a diet or food with good protein quality. Relationships between amino acid intake or protein quality with length gain were assessed using regression models. Length was measured at 6 and 12 months of age and length for age z-score (LAZ) velocity was calculated (ΔLAZ/months). ResultsThe probability of inadequate amino acid intake from breast milk and complementary food that included a lipid-based nutrient supplement (LNS) was 3% for lysine, 0% for tryptophan, threonine, valine, histidine, isoleucine, leucine, sulfur containing amino acids (SAA), and aromatic amino acids (AAA). Without LNS, the probability was 7% for lysine and 0–2% for the other amino acids. The median (interquartile range) DIAAS for complementary food with and without LNS was 0.70 (0.28) and 0.64 (0.32), respectively. Dietary amino acid intake and protein quality were not significantly associated with length gain velocity from 6 to 12 months even after adjusting for confounding factors. ConclusionsThe prevalence of inadequate amino acid intake in 9–10 months old infants in rural Malawi is very low. However, in conditions of frequent clinical or sub-clinical infections this situation may be different. Linear growth at 6–12 months does not appear to be limited by dietary amino acid intake or protein quality in this setting. Funding SourcesThe Bill & Melinda Gates Foundation.

Relationship Between Amino Acid and Energy Intake and Long-Term Growth and Neurodevelopmental Outcomes in Very Low Birth Weight Infants.

Inadequate nutrition may contribute to adverse neurodevelopmental and growth outcomes in very low birth weight (VLBW) infants. A retrospective cohort study was conducted of infants born weighing <1250 g between 2009 and 2010 in a tertiary neonatal intensive care unit. The aim was to investigate whether there was a correlation between the amount of amino acid and calories received in the first 4 weeks of life and neurodevelopment and growth at 2 years. Parenteral amino acid intake in week 2 of life correlated with higher language and motor scores on the 2-year Bayley Scales of Infant and Toddler Development Third Edition (Bayley III). Conversely, higher total amino acid intake during week 1 of life (≥1.5 g/kg/d) was associated with a shorter duration of hospitalization, shorter intensive care stay, fewer days receiving mechanical ventilation, fewer days receiving supplemental oxygen, and a lower incidence of chronic lung disease (CLD). Higher caloric intake in the first 4 weeks correlated strongly with shorter duration of hospitalization, shorter intensive care stay, fewer days on the ventilator, and fewer days receiving supplemental oxygen. In patients with CLD, week 1 and 2 parenteral and total amino acid intake correlated with higher cognitive and motor scores on the Bayley III at 2 years old. Weeks 1-4 amino acid and calorie intake correlated with fewer days on the ventilator, fewer days of supplemental oxygen, and fewer days of hospitalization. Amino acid intake within the first weeks of life correlated positively with neurodevelopmental outcomes at 2 years, and patients with CLD were found to be particularly at risk. Caloric intake may affect protein accretion.

Oral Protein Supplementation Alone Improves Anabolism in a Dose-Dependent Manner in Chronic Hemodialysis Patients

We examined the protein anabolic effects of Pro-Stat 64, a high nitrogen-containing, enzyme-hydrolyzed, tryptophan-fortified, collagen protein supplement administrated during hemodialysis, at two different dosing regimens. This was a randomized, controlled, prospective study with 3 different groups: control, single dose of supplementation, and double dose of supplementation. This study was performed at a clinical research center. Six prevalent chronic hemodialysis (HD) patients were enrolled: 5 males, 1 female, 4 African Americans, and 2 Caucasians. Their mean age was 45 +/- 11 years (S.D.). Two patients were diabetic. Protein turnover studies were performed using amino-acid (AA) balance and primed constant infusion of L-(1-(13)C) leucine. Whole-body protein balance was determined according to substrate kinetics. There were no statistically significant difference at any time point between protocols for blood chemistries and hormonal markers, except for minor variations in plasma glucose. All plasma AA groups displayed decreases during a control study, in which no supplementation was given. Compared with the control group, plasma nonessential AA and total AA concentrations were statistically significantly higher during HD after both single and double doses of supplementation. The forearm arteriovenous AA balance was statistically significantly better for essential, nonessential, and total AA uptake after both single-dose and double-dose supplementation compared with the control group, except for nonessential AA, which was significantly better only after a double dose. Whole-body protein breakdown and net protein balance were statistically significantly better during HD with a double-dose administration in a dose-dependent manner, compared with the control and single-dose groups. Oral AA supplementation alone improves whole-body and skeletal muscle protein anabolism in a dose-dependent manner in chronic HD patients. These data should be taken into account during clinical decision-making or when designing clinical trials of nutritional supplementation.

Use of N‐Acetyl Cysteine for the Treatment of Parenteral Nutrition–induced Liver Disease in Children Receiving Home Parenteral Nutrition

Use of <i>N</i>‐Acetyl Cysteine for the Treatment of Parenteral Nutrition–induced Liver Disease in Children Receiving Home Parenteral Nutrition

The Role of Glucagon in Regulating Chicken Hepatic Malic Enzyme and Histidase Messenger Ribonucleic Acid Expression In Response to an Increase in Dietary Protein Intake

Increased dietary protein intake rapidly (3 h) decreases hepatic malic enzyme and increases hepatic histidase mRNA expression in broiler chicks. A series of experiments was conducted to determine the role that glucagon or a specific mixture of dietary amino acids might have in regulating the rapid changes in mRNA expression of these enzymes, when dietary protein intake is increased. Three hours after the injection of glucagon (240 μ/kg of BW) into the brachial vein of broiler chicks, hepatic malic enzyme mRNA expression was significantly lower and hepatic histidase mRNA expression was significantly greater than the level detected in saline-injected chicks. In addition, broiler chicks fed a high (40 g/ 100 g of diet) protein diet had significantly higher plasma glucagon levels at 1 and 3 h after initial access to this diet than broiler chicks fed a basal (22 g/100 g of diet) protein diet. The plasma glucagon concentration, however, was not different between the chicks fed the 2 dietary protein levels at 2 h after the initial access to the 2 diets. When a mixture of indispensable or dispensable amino acids was added to the basal diet to equal the concentrations of the individual indispensable or dispensable amino acids in the high protein diet, hepatic mRNA expression of malic enzyme and histidase were intermediate to the expression found in chicks fed the basal and high protein diet. The results indicate that glucagon may mediate the changes in the mRNA expression of malic enzyme and histidase in response to dietary protein intake and that total amino acid intake rather than the ingestion of specific amino acids regulates the mRNA expression of malic enzyme and histidase in chicks.

P1162 THE EFFECTS OF GLUTAMINE SUPLEMENTED PARENTERAL NUTRITION ON THE INCIDENCE OF NEC, NOSOCOMIAL INFECTIONS AND BPD AT 36 WEEKS PCA IN ELBW INFANTS.

Introduction: Glutamine is one of the most abundant amino acid in plasma and human milk and may be conditionally essential in premature infants, but is not provided in intravenous amino aced solutions.Under normal conditions glutamine is the prefered respiratory fuel for rapidly proliferating cells such as enterocytes and lymphocytes. Methods: A prospective randomised controlled trial comparing two types of parenteral nutritions involving 36 ELBW infants with birth weight of 590–1250g treated in NICU, randomly allocated to receive either standart or glutamine supplemented PN.Glutamine was added to amino acid solution in ammount of 20% of the total amino acid intake from day 4 for 10 days.Babys were monitored for various health and biochemical indices. Statistical analysis was done using conserning the difference between the proportions using normal approximation. Results: Two babys in control group died. Control Supplemented p-value NEC 4/16 0/18 0,012 Nosocomial Infections 10/16 3/18 NS BPD 36 weeks pca 3/16 3/18 NS Conclusion: Glutamine appears to be save for use in premature infants. Glutamine supplemented PN decrease the incidens of NEC, but did not decrease the incidens of nosocomial infections and BPD in 36 weeks pca.

Effect of composition of ruminally-infused short-chain fatty acids on net fluxes of nutrients across portal-drained viscera in underfed ewes

Four ewes, each fitted with a rumen cannula and with catheters in the mesenteric artery and portal and mesenteric veins, received continuous intrarumen infusions of water or of short-chain fatty acids (SCFA). SCFA infusions were isoenergetic (83 kJ/h) and provided rumen molar proportions (acetate:propionate:butyrate) of 70:20:10, 50:40:10 or 50:20:30. The rumen SCFA production rate with the basal diet was 90.0, 23.1 and 8.8 mmol/h for acetate, propionate and butyrate respectively. Portal net fluxes indicated that 74, 67 and 22-30% of infused acetate, propionate and butyrate respectively, reached the portal vein. Portal net release of beta-hydroxybutyrate increased with SCFA infusions, irrespective of the amount of butyrate infused. Portal net release of lactate decreased with high-butyrate infusion. Portal net uptake of glucose increased with the SCFA infusions. In ewes infused with water, a portal net uptake of total amino acids (AA) was observed. SCFA infusions decreased the uptake of nonessential AA (glutamate, glycine, but not glutamine) and increased the net release of tyrosine and essential AA (isoleucine, leucine). Portal net fluxes of AA were similar with both high-acetate and high-propionate infusions. Lower net uptake of glutamine and net release of most essential AA and some nonessential AA were observed with the high-butyrate infusion. Energetic summation of portal net release was not significantly different between the three SCFA infusions, although it tended to be lower with high-butyrate infusion. This may be related to the higher trophic effect of butyrate on the digestive mucosa.

Effect of diet on amino acid composition of soft faeces and the contribution of soft faeces to total amino acid intake, through caecotrophy in lactating doe rabbits

Abstract Twenty-five New Zealand White × Californian lactating doe rabbits were used to study the effect of different dietary fibre concentrations on the amino acid contribution of soft faeces to the total amino acid intake. Five isoenergetic diets containing 312, 334, 360, 384, and 412 g/kg neutral-detergent fibre (DM basis) were formulated. All diets were designed to maintain the same amino acid pattern. Soft faeces production showed a trend to increase (P = 0·07) as dietary fibre increased. The content of isoleucine (P &lt; 0·01), glutamic acid, leucine and alanine (P &lt; 0·05) in soft faeces decreased as the dietary fibre increased. A trend to decrease with the increase of dietary fibre was also observed for aspartic acid (P = 0·06), lysine (P = 0·07), methionine and valine (P = 0·1). As a consequence, the soft faeces contribution to the total intake of individual amino acids did not vary with the type of diet. The average contribution of soft faeces to the total amino acid intake for the most limiting amino acids of lactating doe rabbits under practical conditions, methionine, threonine and lysine, were 0·17 , 0·21 and 0·18 g/g, respectively.

A survey of feeding practices in infants with phenylketonuria

Summary Background: Although the management of phenylketonuria (PKU) in infancy and early childhood is a critical part of the overall care of the disorder, there are few guidelines on infant feeding in this condition. This survey was undertaken to establish the practices of dietitians from major PKU centres in Australia and the UK. Methods: A postal questionnaire examining infant feeding practices was sent to dietitians at nine major PKU centres in the UK and four in Australia, with each dietitian describing the infant feeding process in their last five infants. A total of 63 infants were investigated. Results: A lower than expected incidence of infants with PKU were breast fed at the time of diagnosis: 28% of infants in the UK and 41% from Australia. Amino acid intake varied between 2.0 g kg−1 day−1 to 3.5 g kg−1 day−1 with 86% of dietitians calculating total amino acid intake derived from both protein substitute intake and normal infant formula. Amino acid intake was not calculated in breast‐fed infants. In breast‐fed infants, phenylalanine‐free protein substitute was always given before breast feeds. In bottle‐fed infants, normal infant formula was given before phenylalanine‐free protein substitute in 75% of infants. Solids were usually introduced between 3 and 6 months and phenylalanine‐free solids were given initially to the majority of infants. Most problems were seen when introducing a more concentrated phenylalanine‐free protein substitute to maintain the required amino acid intake in older infants. Age of introduction varied between 4 and 12 months and type of approach included concentrating infant protein substitutes, use of L‐amino acid protein substitutes only, or L‐amino acid protein substitutes with added carbohydrate, vitamins and minerals. Conclusions: There appeared to be no uniform policy of infant feeding in PKU and more work is needed correlating practices to develop national and even international protocols for management.

Effect of glucose on ureagenesis during exercise in amino acid-infused dogs

The purpose of this study was to investigate the effect of glucose administered with amino acids before and during exercise on hepatic ureagenesis. Eight mongrel dogs subjected to treadmill running for 150 minutes at 10 km/h on a 12% incline were intravenously infused with either a mixture of amino acids and glucose (AAG) or amino acids alone (AA). The infusion was started 60 minutes before exercise and continued until the end of exercise. The rate of urinary urea excretion increased after infusion of both AAG and AA. However, the rate of urinary urea excretion was significantly lower in the AAG group versus the AA group during the first 1.5 hours of the recovery period ([R0 to R90] 514 ± 24 v 637 ± 24 mg/h, mean ± SE, P < .05). Moreover, hepatic urea output was decreased during AAG versus AA infusion (229 ± 62 v 367 ± 55 μg/kg/min, P < .05). Hepatic glucose production during exercise was also significantly lower in AAG versus AA infusion (354 ± 54 v 589 ± 56 mg/kg, P < .05). On the other hand, no difference was observed in hepatic total amino acid uptake between the groups. Thus, these results indicate that AAG administered before and during exercise appears to reduce hepatic ureagenesis due to reduced hepatic gluconeogenesis as compared with administration of AA alone. These findings also suggest that nitrogen retention is enhanced by glucose administered during exercise.

Uptake of labelled phenylalanine into different blood fractions in the portal vein and cranial mesenteric vein of lambs

SUMMARYFour lambs (mean 27 kg liveweight) offered 900 g/day lucerne chaff were prepared with catheters in the portal vein (PV), cranial mesenteric vein (CMV), femoral artery (FA) and abomasum. L-[2,6-3H]phenylalanine (Phe) and14C-(Phe)casein were infused into the abomasum in separate experiments. Concurrent samples of blood from the PV, CMV and FA were prepared as four fractions: plasma, deproteinized whole blood, free Phe in deproteinized whole blood, and whole blood. Ratios of net label uptakes in different blood fractions indicated that red blood cells and blood proteins were unlikely to contribute to net Phe uptake into the PV or CMV. Small peptides may have contributed up to 20% to total appearance of Phe in the PV and CMV. However, net uptake of peptides from the lumen was probably zero. It was concluded that the Phe uptake and, by implication, total amino acid uptake from the lumen of the small intestine into the PV and CMV were as free amino acids.

Recommendations for protein and amino acid intake in phenylketonuric patients.

The methods for the determination of protein requirements are reviewed and the difficulties in achieving the recommendations of the dietary management of phenylketonuria proposed by a Medical Research Council Working Party on Phenylketonuria using currently available low phenylalanine (Phe) protein substitutes and low protein foods are examined. These recommendations are that all infants whose blood Phe concentrations exceed 600 mumol/l in the presence of a normal or low plasma tyrosine and an otherwise normal plasma amino acid profile while receiving a normal protein intake (2-3 g/kg/day), should start a low Phe diet immediately. Infants whose blood Phe concentrations remain persistently between 400 and 600 mumol/l for more than a few days should also start treatment. The diet should contain a protein substitute which is Phe free (or at least very low in Phe) and otherwise nutritionally complete with a composition sufficient to provide 100-120 mg/kg per day of tyrosine and a total amino acid intake of at least 3 g/kg per day in children under 2 years of age. In children over 2 years the intake of amino acids should be maintained at a level of 2 g/kg per day. The protein substitute should be spread as evenly as possible through the 24 h. Blood Phe concentrations should be maintained between 120 and 360 mumol/l. In children aged over 10 years it is suggested that the protein substitute should supply the protein reference nutrient intake + 50%. An upper blood Phe limit of 480 mumol/l rather than 360 mumol/l may be acceptable in school age children. Adults and adolescents should continue treatment with the aim to maintain blood Phe concentrations no higher than 700 mumol/l. During the period before conception and during pregnancy women should aim to have plasma Phe concentrations between 60-250 mumol/l.

WEGENER'S GRANULOMATOSIS

Early postnatal growth failure is well described in very preterm infants. It reflects the nutritional deficits in protein and energy intake that accumulate in the first few weeks after birth. This coincides with the period of maximum parenteral nutrition (PN) dependency, so that protein intake is largely determined by intravenous amino acid (AA) administration. The contribution of PN manufacture, supply, formulation, prescribing and administration to the early postnatal nutritional deficit is discussed, focusing on total AA intake. The implications of postnatal deficits in AA and energy intake for growth are reviewed, with particular emphasis on early head/brain growth and long-term neurodevelopmental outcome. The rationale for maximising AA acid intake as soon as possible after birth is explained. This includes the benefits for very early postnatal nutritional intake and metabolic adaptation after birth. These benefits relate to total AA intake and so have to be interpreted with some caution, given the very limited evidence base surrounding the balance of individual AAs in neonatal PN formulations. This work mostly predates current nutritional recommendations and therefore may not provide a true reflection of individual AA utilisation in current clinical practice.

Decreased cysteine and proline synthesis in parenterally fed, premature infants

Little is known about the amino acid (AA) biosynthetic capacity and requirements of premature infants. This study assessed the synthesis of seven biochemically nonessential AA from a universal precursor, glucose, in stable, parenterally fed, premature neonates. Seven infants (six boys, one girl) were studied at a mean age of 6.3 ± 0.6 (SEM) days; mean gestational age was 29.7 ± 1.3 (SEM) weeks, and mean birth weight was 1,222.8 ± 176.5 (SEM) grams. All infants were parenterally fed a mixture of 7.5% to 12.5% dextrose and 2.2% Trophamine, with or without lipid. Mean caloric intake was 93 ± 8.4 (SEM) kcal/kg/d, and total AA intake was standardized at 2.86 g/kg/d AA, plus supplemental cysteine (30 mg/g AA/d). Each infant received a 4-hour continuous, unprimed intravenous infusion of a stable isotope tracer of D-[U 13C] glucose (200 mg/kg). Blood samples were obtained before and at the end of the infusion. Conversion of the glucose tracer into seven biochemically nonessential AA (cysteine [Cys], proline [Pro], aspartate [Asp], serine [Ser], glutamate [Glu], alanine [Ala], and glycine [Gly]) was assessed by measuring their isotopic enrichment in plasma, using gas chromatography/mass spectrometry ( GC MS ), and expressed as mole percent excess (MPE) (mean ± SEM). The isotopic enrichment of plasma glucose was also measured using GC MS . Free plasma AA concentrations (mean ± SD) were measured using an automated amino acid analyzer. Mean MPE for M + 1, M + 2 and M + 3 Cys, and for M + 1 and M + 3 Pro were not significantly different from 0; M + 2 Pro barely achieved statistical significance ( P = .048). In contrast, there was significant ( P < .05) enrichment of all isotopomers of all the other test AA except M + 2 Ala ( P = .06). The mean free plasma Cys concentration (29.2 ± 13.4 μmol/L) was five-fold lower than the published value for term infants (153 ± 25.5 μmol/L), despite supplementation. Detectable enrichment of all glucose isotopomers confirmed precursor incorporation into the glycolytic/gluconeogenic pathways; the M + 6 isotopomer (precursor) enrichment was 6.87 ± 0.53 MPE. These results provide in vivo evidence to suggest that Cys and Pro are essential amino acids in parenterally fed, premature neonates.

Disposal of exogenous amino acids by muscle in patients with chronic renal failure

Muscle exchange of amino acids (AAs) was evaluated by using the arteriovenous-difference technique across the leg in seven patients with chronic renal failure (CRF) and eight control subjects before and for 75 min after the ingestion of an AA mixture simulating an animal-protein meal. Total AAs increased in arterial blood much more in patients with CRF after AA ingestion than in control subjects, as a consequence of an exaggerated increase in nonessential AAs (NEAAs) (+127%). Moreover, total AAs were taken up by the leg in larger amounts than in control subjects (+71%, P < 0.0025) because of increased uptake of NEAAs (+156%, P < 0.005). Branched-chain AA uptake by the leg was, in absolute values, similar to that of control subjects; however, because of the increased uptake of total AAs, branched-chain AA uptake was only 30% of total AA extraction, compared with 46% in control subjects. Abnormalities in AA uptake by muscle paralleled those in arterial AAs. In fact the same AAs that increased abnormally in blood were taken up by the leg at higher rates than in control subjects. Variations in arterial concentrations and muscle uptake of AAs were inversely related to arterial bicarbonate concentration, suggesting a role for acid-base status in modifying both the arterial supply and muscle metabolism of AAs. Results indicate that in CRF patients the normal pattern of postprandial AA repletion is disrupted. Muscle tissue faces the increased and unbalanced postprandial supply of AAs with an augmented and unbalanced uptake. Data are consistent with an abnormal use of exogenous AAs in CRF patients, possibly induced by metabolic acidosis.

Supplemental alanylglutamine, organ growth, and nitrogen metabolism in neonatal pigs fed by total parenteral nutrition.

The objective of this study was to determine whether supplemental glutamine (alanylglutamine dipeptide) is effective in preventing small intestinal mucosal atrophy associated with total parenteral nutrition and whether it affects the growth of other organs in neonatal pigs. We compared organ growth, intestinal enzyme activity, and plasma nitrogen metabolites in 4-day-old pigs randomly selected to receive total parenteral nutrition supplemented with 0 g, 2.0 g, or 4.5 g of glutamine per deciliter for a total amino acid intake of either 11 or 25 g.kg-1.d-1 for 7 days. Glutamine supplementation increased (60% to 100%) plasma concentrations of glutamine, urea nitrogen, ammonia, and both jejunal villus height and surface area, but it did not significantly affect jejunal mucosal protein and DNA masses or the relative growth of liver, kidneys, and brain. No histologic evidence of tissue toxicity was found. Supplementing large amounts of glutamine (alanylglutamine dipeptide) did not completely prevent total parenteral nutrition-associated intestinal mucosal atrophy but did improve villus morphology without affecting vital organ growth or histology.

Independent and combined actions of interleukin-1β, tumor necrosis factor α, and glucagon on amino acid metabolism in the isolated perfused rat liver

Conflicting reports concerning the hepatic effects of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in the metabolic response to injury led us to investigate the influence of physiological concentrations of these cytokines on amino acid metabolism in the isolated perfused rat liver. IL-1β was ineffective at a concentration of 1 ng/mL, whereas TNFα (0.7 ng/mL) reduced the uptake of some of the main gluconeogenic amino acids (alanine, −55.3 ± 4.9 v −72.9 ± 13.7 nmol·min −1·g −1 in controls, P < .05) without affecting urea synthesis. TNFα also increased glucose uptake by 237% and inhibited that of free fatty acids (−1.6 ± 1.4 v −9.9 ± 6.7 nmol·min −1·g −1 in controls, P < .05). IL-1β and TNFα potentiated glucagon-induced total amino acid uptake by 56% and 87%, respectively. They also affected glucagon-activated gluconeogenesis, leading to an initial potentiation of glucose release. Thereafter, IL-1β inhibited glucagon action, leading to an hepatic uptake of glucose. These results indicate that (1) in the conditions of the study, IL-1β has no direct effect on hepatic amino acid exchanges and utilization; (2) TNFα, which exerted an inhibitory effect on these parameters, could be involved in the reduced amino acid exchanges during the end stage of sepsis; (3) the TNFα-induced increase in glucose uptake could be related to an inhibition of gluconeogenesis and/or to the activation of glucose utilization by Kupffer cells; (4) IL-1β and TNFα both potentiate the action of glucagon on hepatic amino acid uptake and utilization; and (5) complex interactions between Kupffer cells and hepatocytes on the one hand and between cytokines and hormones on the other hand could account for the differences in hepatic metabolism according to the stage of the response to injury.