Classic dengue fever affects levels of circulating antioxidants

OBJECTIVE: We studied alterations of circulating antioxidant nutrients in patients with classic dengue fever in the tropical lowlands of Guatemala. METHODS: In nine patients with dengue fever and 12 healthy Guatemalan control subjects, we assessed plasma concentrations of retinol, alpha-tocopherol, beta-carotene, glutathione, taurine, thiobarbituric acid-reactive species, and total antioxidant status. Control subjects were assessed twice within 48 h to account for day-to-day variations. Febrile patients with dengue fever were examined on the day of admission to the hospital, at discharge after defervescence (approximately 5 d after admission), and 7 d thereafter. RESULTS: In patients with dengue fever, increases in plasma concentrations of retinol and beta-carotene were seen, whereas decreases were observed for glutathione and total antioxidant status. As compared with the reference group, patients with dengue fever had lower retinol concentrations in the acute phase of the disease and lower glutathione concentrations 7 d after discharge. Further, thiobarbituric acid-reactive species levels were higher in the dengue fever patients as analyzed by unpaired t test. CONCLUSION: Using dengue fever as a model for the metabolic response to an acute, self-limited tropical viral infection, the present findings suggest slight turbulence of the antioxidant system that may be a response to or a consequence of the viral inflammatory process.     

Amino acid kinetics in patients with sepsis

BACKGROUND: In patients with sepsis and systemic inflammatory response syndrome, amino acid extraction by the liver is enhanced, resulting in decreased plasma amino acid concentrations. Systematic investigations of the elimination of intravenously infused amino acids have not been performed. OBJECTIVE: The objective of this study was to compare the elimination of 17 amino acids in patients with sepsis and in healthy control subjects. DESIGN: Elimination of amino acids was evaluated in 9 patients with sepsis and in 8 healthy control subjects by using a combined loading and maintenance infusion of 375 mg amino acids/kg body wt for 60 min. Pharmacokinetic variables were analyzed from plasma curves. RESULTS: With the exception of lysine, methionine, glutamate, ornithine, phenylalanine, and tyrosine, plasma concentrations of amino acids were lower in the patients with sepsis than in the control subjects; phenylalanine was the only amino acid whose plasma concentration increased (P < 0.001). In patients with sepsis, whole-body clearance (Cl(tot)) of total amino acids was 74% higher than in control subjects (x +/- SEM: 13,161 +/- 1659 and 7566 +/- 91 mL/min, respectively; P < 0.01), the Cl(tot) of essential amino acids was 64% higher (P < 0.02), that of nonessential amino acids was 82% higher (P < 0.01), and that of both branched-chain amino acids and glucogenic amino acids was 97% higher (P < 0.001). With the exception of phenylalanine, ornithine, proline, and glutamate, the Cl(tot) of all amino acids was elevated. The Cl(tot) of phenylalanine and ornithine decreased slightly (NS). CONCLUSIONS: In patients with sepsis, plasma concentrations of most amino acids are greatly decreased and the elimination of amino acids from the intravascular space during intravenous infusion is greatly enhanced.     

Appearance of individual amino acid concentrations in arterial blood during steady-state infusions of different amino acid formulations to ICU patients in support of whole-body protein metabolism

BACKGROUND: Previous work has demonstrated a relationship between arterial amino acid concentrations and uptake of amino acids across peripheral tissues in healthy volunteers, as well as in chronically and acutely ill patients. The aim of the present study was to evaluate whether different amino acid profiles in commercially available amino acid formulations are translated into significantly different arterial amino acid concentrations presumably high enough to promote protein metabolism in intensive care unit (ICU) patients. METHODS: Nonprotein calories (60% glucose: 40% lipid) were simultaneously and constantly infused over 72 hours. Different free amino acid solutions were infused at random to each patient for 24 hours in order to determine the appearance of steady-state arterial concentrations of individual amino acids. Basal metabolic and nutrition states were defined after a 12-hour infusion period with glucose in each patient. Healthy volunteers receiving a standardized oral meal served as reference subjects in measurements of venous amino acid concentrations after normal oral food intake. RESULTS: The sum of all amino acids in arterial plasma increased significantly during steady-state infusions of all the free amino acid solutions vs basal state in ICU patients. Only glutamine, taurine, and tyrosine did not increase at all vs basal state during steady-state infusions of the 3 formulations. Alanine, arginine, citrulline, glycine, histidine, serine, methionine, phenylalanine, valine, and ornithine showed different concentration among the amino acid solutions during infusions. Healthy volunteers had significantly higher overall concentrations of amino acids in both fasted and fed state compared with ICU patients, which indicates that free amino acid solutions remain a limiting component in artificial nutrition to patients to promote arterial amino acid concentrations in the artificially fed state. CONCLUSIONS: It appears important to continue further improvement of composition profile in solutions of free amino acids to promote adequate uptake across organ beds in promotion of protein balance in artificially nourished patients.     

Plasma amino acid concentrations and amino acid ratios in normal adults and adults heterozygous for phenylketonuria ingesting a hamburger and milk shake meal

Plasma amino acid concentrations were measured and selected amino acid ratios were calculated in 12 normal adults and 12 adults heterozygous for phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g protein/kg body wt. Plasma concentrations of all amino acids increased significantly over baseline after meal ingestion in both groups, reaching the highest mean values 3-5 h after meal ingestion. Plasma phenylalanine concentrations were significantly higher in heterozygous than in normal subjects both before and at all times after meal ingestion. The absolute increase in plasma phenylalanine concentration over baseline and the area under the plasma phenylalanine concentration-time curve were approximately twice as large in heterozygous as in normal subjects. However, the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids did not increase significantly over baseline, but rather decreased.     

Serum Amino Acid Concentrations in Patients Receiving Total Parenteral Nutrition with an Amino Acid Plus Dextrose Mixture

The results of monitoring the serum amino acid concentrations during three infusion regimens using a 5:4 mixture of 70% glucose and the synthetic L-amino acid solution, Synthamin 17 (Travasol) are reported. Twelve stabilized patients received continuous total parenteral nutrition (TPN), eight of whom were subsequently placed on a second regimen of cyclical feeding. A separate group of five patients was infused with amino acids, both with and without simultaneous glucose. The serum amino acid concentrations indicated that the supply of valine, leucine, isoleucine, lysine, and histidine, and the synthesis of taurine from the infused methionine was suboptimal, particularly if the period of TPN was prolonged. The synthesis of tyrosine from phenylalanine appeared to be inversely proportional to the infusion rate of the TPN mixture, in particular the glucose component, resulting in depressed tyrosine and increased phenylalanine concentrations in serum during continuous iv nutrition. Cyclical infusions, on the other hand, permitted the tyrosine and phenylalanine concentrations to return to normal during the noninfusion stage of the cycle. Amino acid measurements enabled us to design an amino acids additive mixture which normalized the serum concentrations in three long-term home parenteral nutrition patients. As a result of these investigations serum amino acid measurements are used routinely to monitor the efficacy of TPN and accommodate any specific amino acid requirements of individual patients. (Journal of Parenteral and Enteral Nutrition 8: 535–541, 1984)     

Amino acid metabolism in uremia

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A "New Formula" has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap     

Amino acid metabolism in uremia.

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A “New Formula” has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap     

Epinephrine transiently increases amino acid disappearance to lower amino acid levels in humans.

BACKGROUND: Infusion of epinephrine decreases plasma amino acid concentrations. However, the mechanism by which this decrement occurs is not well characterized. METHODS: Epinephrine was infused (40 ng/kg/min) for 2 hours into eight normal healthy adults. The essential amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]phenylalanine were infused before and during the epinephrine infusion and blood samples obtained to determine amino acid rates of appearance and disappearance from the time course of change in amino acid concentration and tracer enrichments. RESULTS: Epinephrine infusion decreased plasma leucine and phenylalanine concentrations over a period of 30 to 90 minutes after the start of the epinephrine infusion. Epinephrine infusion induced an immediate decrement in tracer enrichments. These changes defined sharp increases in both rate of appearance and rate of disappearance. By 30 minutes of epinephrine infusion, the rate of amino acid appearance from proteolysis had returned to baseline, but the rate of amino acid disappearance remained elevated for 90 minutes before returning to baseline. It was the protracted increase in amino acid disappearance that was responsible for the lowering of plasma amino acid concentrations. After this acute response, rates of amino acid appearance and disappearance returned to normal whereas plasma amino acid levels remained suppressed. CONCLUSIONS: Epinephrine transiently affects both rates of amino acid appearance and disappearance, with the net effect being increased in amino acid disappearance. However, epinephrine lowers amino acid concentrations beyond the period that it affects kinetics. These results suggest that the effect of epinephrine on amino acid metabolism is not detrimental and that epinephrine allows amino acid metabolism to proceed normally but at lower concentrations of amino acids.     

Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults (n = 60, 38.2 ± 1.8y) completed graded dosages of either phenylalanine or serine supplement (3, 6, 9 and 12 g/d) for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality and mental self-assessment. At low dosages, minor changes in serum electrolytes and plasma non-essential amino acids glutamine and aspartic acid concentrations were observed. Serine increased its plasma concentrations at high supplemental dosages (9 and 12 g/day), and phenylalanine increased plasma tyrosine concentrations at 12 g/day, but those changes were not considered toxicologically relevant. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of phenylalanine or serine without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of phenylalanine and serine supplementation in healthy adult males was determined to be 12 g/day.     

Plasma amino acid concentrations in healthy and cognitively impaired oldest-old individuals: associations with anthropometric parameters of body composition and functional disability

Only a few reports exist of plasma amino acid profiles in the oldest-old, and none exist of the oldest-old with cognitive problems. Therefore, we measured fasting plasma amino acid concentrations in twenty-three healthy community-dwellers aged 90-103 years (group A); eighteen community-dwellers with mild cognitive impairment without dementia aged 91-104 years (group B); thirty-three patients with dementia aged 96-100 years (group C); and sixty healthy young controls aged 20-50 years. Biochemical and anthropometric parameters, and the basic activities of daily living (ADL) were also measured. Independent of cognitive status, in all oldest-old groups, essential:non essential amino acids (EAA:NEAA) was lower than in young controls and positively associated with body muscle mass. Patients with dementia were further characterized by a negative association between EAA:NEAA and the number of dependent ADL. All oldest-old groups had higher values of tyrosine:other large neutral amino acids (LNAA) than young controls. Groups B and C also had a higher phenylalanine:other LNAA. These data show that abnormalities in plasma amino acid profile are common in oldest-old individuals independent of their cognitive status, but that, in oldest-old patients with dementia, they are associated with functional disability. The abnormalities in phenylalanine and tyrosine plasma availability could contribute to the cause or aggravation of concurrent cognitive problems because these amino acids are neurotransmitter precursors and compete with other LNAA for transport into the brain.     

Plasma Amino Acids in Children under Two Years of Age with Severe Undernutrition. Increase of Taurine in Kwashiorkor

There are many reports documenting modifications of different plasma components in undenutrition, including the protein-calorie (marasmus) or the protein deficiency (kwashiorkor) subtypes. However, there is no detailed study on the effect of undernutrition on plasma amino acid pattern during the first two years of life, a critical period of biological development in humans. The plasma concentrations of 19 amino acids were analysed in 32 children under two years of age presenting severe undernutrition: marasmus, kwashiorkor or mixed picture. The subjects were admitted to the hospital as inpatients and received a balanced diet as the only treatment. Samples of venous blood were taken from nine patients at discharge and plasma amino acid profile was compared with the preadmission profile. A healthy control group included 11 children visiting the hospital for regular pediatric examination. At the time of admission the amino acid levels of tyrosine, tryptophan and leucine were significantly lower in the undernourished group of children compared to controls. On the other hand, levels of aspartate were higher in the children with malnutrition. These changes in amino acids were not present at the time of discharge from hospital after diet therapy. Taurine concentration was higher in undernourished children and remained high at the time of discharge. Compared with the control group, marasmic children showed increases in plasma aspartic acid and serine, and decrease in trypthophan. Kwashiorkor children had lower levels of tyrosine, trypthophan and leucine, but higher levels of taurine. The elevation of taurine was not corrected by diet therapy.     

High levels of dietary amino and branched-chain alpha-keto acids alter plasma and brain amino acid concentrations in rats

Plasma and brain amino acid and plasma branched-chain alpha-keto acid (BCKA) concentrations were measured in rats fed diets containing high levels of individual amino and alpha-keto acids. Consumption of a low-protein (9% casein) diet high in leucine or alpha-ketoisocaproate depressed plasma concentrations of isoleucine and valine and their respective keto acids, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. High dietary levels of alpha-keto-beta-methylvalerate or alpha-ketoisovalerate (but not of isoleucine or valine) depressed plasma concentrations of the other BCKA and their respective branched-chain amino acids (BCAA). Consumption of a low protein, high phenylalanine diet depressed plasma concentrations of both BCAA and BCKA. Brain large neutral amino acid pools of rats fed all low-protein, high-amino acid diets were depleted. Consumption of diets high in individual BCKA increased brain concentrations of aromatic amino acids. In this study of rats allowed to feed for only 6 h/d, elevated brain phenylalanine concentration was associated with a significant depression of food intake, whereas elevated brain BCAA concentrations were not. Also, elevated plasma BCKA concentrations, comparable with those observed in maple syrup urine disease, were accompanied by elevations in concentrations of aromatic amino acids in brain but not in plasma.     

Influence of dietary protein concentration on the oxidation of phenylalanine by the young pig

1. Piglets were weaned at 3 d of age and reared to 2.5 kg on a liquid diet in which the protein was supplied by dried skim milk and a mixture of free amino acids. The oxidation of L-[1-14C]phenylalanine was measured as an indication of the partition of amino acids between retention and catabolism in pigs (2.5 kg) offered meals containing varied concentrations of crude protein (nitrogen x 6.25). 2. The dietary protein concentration was varied either by increasing the inclusion of a mixture of free amino acids in a series of diets containing 100 g protein/kg from skim milk, or by increasing the level of inclusion of the skim milk in a series of diets containing the equivalent of 100 g protein/kg from the free amino acid mixture. 3. The oxidation of phenylalanine was minimized by dietary protein concentrations of 240 and 258 g/kg for the diets containing increasing concentrations of free amino acids or skim milk respectively. 4. These results show that a mixture of free amino acids is used more effectively than intact protein for promoting retention of essential amino acids. 5. The recovery of radioactivity in expired carbon dioxide was inversely related to the recovery of radioactivity in liver tissue when the concentration of dietary crude protein was increased from deficient to adequate, demonstrating that the fractional oxidation of the indicator amino acid was inversely related to protein synthesis.     

CE-MS检测胃癌患者的尿液氨基酸代谢变化

目的检测胃癌患者尿液的游离氨基酸代谢轮廓,将癌症组和正常对照组进行比较,筛选出具有诊断意义的氨基酸,探讨胃癌患者尿液中氨基酸代谢的变化规律和临床意义。方法收集胃癌患者与健康成人晨尿。采用移动反应界面富集法的毛细管电泳质谱联用技术对尿样中游离氨基酸轮廓进行检测,结合氨基酸标准品的定性定量分析,并对所得数据运用SPSS17.0进行统计学处理,得到有意义的氨基酸。结果胃癌患者尿液代谢轮廓较正常组有明显变化。与正常组相比,胃癌组尿液中的异亮氨酸、缬氨酸、精氨酸水平升高(P﹤0.05),组氨酸、蛋氨酸、天冬氨酸含量降低(P﹤0.05)。主成分胃癌患者尿液代谢较正常组有明显变化;早期或进展期胃癌患者尿液代谢轮廓亦有明显变化。结论毛细管电泳质谱检测方法可以较好的揭示正常组与胃癌的尿液代谢信息,此方法具有可行性,简便,快速。结果表明,毛细管电泳质谱检测胃癌患者尿液中氨基酸代谢对胃癌诊断与筛查具有重要的临床意义。     

终末期肾病患者血清氨基酸水平的变化

目的用高效毛细管电泳法分析终末期肾病（ESRD）患者与正常人血清游离氨基酸水平的变化，并探讨氨基酸与患者血白蛋白、血红蛋白和转铁蛋白的相互关系。方法选择ESRD（内生肌酐清除率〈0．25ml／s）尚未开始透析的患者共40例，除外活动性肝脏疾病、急性感染、慢性特异性感染和肿瘤患者；健康对照者24例。常规检测血白蛋白、转铁蛋白、血红蛋白和肌酐的水平，用高效毛细管电泳仪检测血清氨基酸水平。结果与正常人相比，ESRD患者血清非必需氨基酸中酪氨酸浓度显著降低，而半胱氨酸、脯氨酸浓度显著升高（P〈0．05）；缬氨酸／甘氨酸、丝氨酸／甘氨酸比值显著降低（P〈0．05）；血清必需氨基酸中色氨酸、缬氨酸、苏氨酸浓度显著降低（P〈0．05）。甘氨酸与红细胞压积、丝氨酸／甘氨酸比值与红细胞压积和血红蛋白值呈显著正相关，半胱氨酸、缬氨酸和缬氨酸／甘氨酸比值与白蛋白（ALB）呈显著正相关。进一步将ALB按ALB〉30g／L、20g／L≤ALB≤30g／L、ALB〈20g／L分层分析，结果显示3组间缬氨酸浓度差异具有显著性（P=0．029）。酪氨酸、脯氨酸、甘氨酸、缬氨酸与转铁蛋白呈显著正相关（P=0．007，P=0．046，P=0．008，P=0．009）。结论ESRD患者血清游离氨基酸代谢与正常人相比，差异具有显著性；必需氨基酸普遍下降；非必需氨基酸高低不一。部分氨基酸的代谢可能影响患者白蛋白、血红蛋白和转铁蛋白的合成。     

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.     

Oxidation of an indicator amino acid by young pigs receiving diets with varying levels of lysine or threonine, and an assessment of amino acid requirements

The catabolism of [14C]phenylalanine was used to indicate the effects of varying the dietary level of lysine and threonine on the retention of dietary amino acids by 2-week-old pigs receiving diets containing skim milk and a mixture of free amino acids. Reducing the dietary level of lysine from 16 to 12 g/kg had no influence on phenylalanine oxidation, reducing the lysine level from 12 to 11 then to 10 g/kg caused an almost linear increase in phenylalanine oxidation whereas further reduction to 9 or 8 g/kg resulted in a less-marked increase in phenylalanine oxidation. This showed that 12 g lysine/kg was required to maximize amino acid retention and indicated that lysine was conserved more effectively at low dietary concentrations than at dietary concentrations approaching the requirement. Reducing the dietary level of threonine from 8 to 6 g/kg had no influence on phenylalanine oxidation, whereas further reduction to 4 g/kg caused a linear increase in phenylalanine catabolism showing that 6 g threonine/kg was required to maximize amino acid retention. Reduction of the levels of lysine, threonine and methionine from the generous levels characteristic of a diet containing 240 g protein from skim milk/kg, to the requirement levels determined separately in the presence of the generous levels of all the other amino acids, resulted in a twofold increase in phenylalanine catabolism. This shows that the pig seems able to conserve limiting intakes of a single amino acid, but not if the intakes of two or three amino acids are limiting.     

Proline as an essential amino acid for the young pig

1. The catabolism of L-[1-14C]phenylalanine was used to indicate the effects of single amino acid supplementation of an inadequate protein diet (200 g crude protein (nitrogen x 6.25)/kg) on the utilization of dietary amino acids in pigs of 2.5 kg body-weight reared on an adequate protein diet (240 g crude protein/kg) containing skim milk and a mixture of free amino acids. 2. The oxidation of phenylalanine was decreased by the addition of proline or arginine to the inadequate protein diet but not by the addition of threonine, methionine, lysine or a mixture of essential amino acids, indicating that proline and arginine were limiting the utilization of dietary amino acids in the inadequate protein diet. 3. Dietary proline concentrations of 13.9 and 14.2 g/kg minimized phenylalanine oxidation in diets containing 200 or 260 g protein/kg. This indicates a dietary proline requirement of 14 g/kg. 4. Increasing the dietary arginine concentration in a diet containing 240 g protein/kg showed that an arginine concentration of 5.1 g/kg minimized phenylalanine oxidation. However, increasing the arginine concentration in a diet containing 200 g protein/kg increased phenylalanine oxidation, suggesting an amino acid imbalance involving arginine at this lower level of protein.     

Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal amino acid pools in experimental maternal phenylketonuria

BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p-chlorophenylalanine, and L-phenylalanine in the diet. OBJECTIVE: We studied whether a dietary mixture of several large neutral amino acids (LNAAs) would improve fetal brain growth and normalize the fetal brain amino acid profile in a rat model of maternal PKU induced by DL-alpha-methylphenylalanine (AMPhe). DESIGN: Long-Evans rats were fed a basal diet or a similar diet containing 0.5% AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of gestation in experiments to test various mixtures of LNAAs. Maternal weight gains and food intakes to day 20, fetal body and brain weights at day 20, and fetal brain and fetal and maternal plasma amino acid concentrations at day 20 were measured. RESULTS: Concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were higher and fetal brain weights were lower in rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, fetal brain growth was higher and concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were lower in rats fed the AMPhe + Phe diet plus LNAAs than in rats fed the diet containing AMPhe + Phe alone. CONCLUSION: LNAA supplementation of the diet improved fetal amino acid profiles and alleviated most, but not all, of the depression in fetal brain growth observed in this model of maternal PKU.