Amino Acid Load Research Articles

No effect of acute tryptophan depletion on verbal declarative memory in young persons with ADHD

Animal experiments and studies in adults have shown that the neurotransmitter serotonin (5-HT) plays an important role in learning and memory processes. However, data on this relationship in young persons are scarce, and neurodietary research in this age group is limited compared with the extensive literature on adults. Here, we aimed to explore the effects of a diminished central nervous 5-HT synthesis, which is achieved by acute tryptophan depletion (ATD) Moja-De , on memory function in young males with attention deficit hyperactivity disorder (ADHD). Twenty-two male patients with ADHD (ages 9-15 years, mean 10.95 ± 1.17 years) received ATD, thus diminishing central nervous 5-HT synthesis, and a tryptophan-balanced amino acid load (BAL) in a randomized, double-blind, within-subject, crossover design study. Approximately 1.7 h after administration of ATD/BAL, verbal declarative memory was assessed using the 'Auditory Verbal-Learning-Test' (AVLT). There were no significant effects of ATD administration on verbal declarative memory function. In this study, changes in 5-HT neurotransmission were not associated with specific aspects of verbal declarative memory in young persons with ADHD. Future studies with healthy control groups that address effects of covarying attentional processes are warranted.

Acute tryptophan depletion does not improve endurance cycling capacity in a warm environment

Newsholme's theory of central fatigue suggests that acute tryptophan depletion should improve endurance exercise capacity in a warm environment by reducing serotonergic activity in the brain. Eight males cycled to volitional exhaustion at 55 % VO(2) peak in 30.1 ± 0.5 °C and 30 ± 7 % relative humidity on two separate occasions, after consuming either an amino acid load to deplete their circulating tryptophan concentration (TD), or a control amino acid load (CON). Blood samples were taken before ingesting the amino acids, before the start of exercise, every 15 min during exercise and at the point of exhaustion. Heart rate (HR), core (Tc) and skin (Tsk) temperatures and ratings of perceived exertion (RPE) and thermal comfort (TC) were also monitored every 10 min during exercise. Plasma tryptophan (P = 0.003) and free tryptophan (P < 0.001) concentrations, and the free tryptophan to branched-chain amino acid ratio (P = 0.004) were all lower on the TD trial than on the CON trial. There was no difference in endurance exercise capacity (TD 99.2 ± 24.4 min as compared to CON 108.4 ± 21.6 min; P = 0.088). There was a tendency for HR (P = 0.053) and Tc (P = 0.069) to be higher on the TD trials. There were no differences for any of the other parameters. Endurance cycling capacity in a warm environment is not improved by acute tryptophan depletion, suggesting tryptophan availability is not a significant factor in the development of fatigue in such situations.

Acute tryptophan depletion in accordance with body weight: influx of amino acids across the blood–brain barrier

Acute tryptophan depletion (ATD) is a method of reducing central nervous serotonin (5-HT) synthesis in humans by administering an amino acid (AA) beverage lacking in tryptophan (TRP), the physiological precursor of 5-HT. However, to date, the use of conventional ATD protocols in children and adolescents was limited due to frequently observed side effects (e.g., vomiting and nausea). This study investigated the effects of diminished central nervous system 5-HT synthesis on plasma concentrations of relevant AAs and TRP influx into the brain in 24 healthy young adults using the ATD procedure Moja-De, a test protocol that has been used in preliminary research in youths. Twenty-four healthy participants received ATD and a TRP-balanced amino acid load (BAL) using a randomized double-blind within-subject crossover design. Plasma concentrations of the relevant AAs that compete with TRP on the same transport system were assessed at baseline and 90, 180, and 240 min after ATD/BAL intake. TRP influx across the blood–brain barrier was calculated using Michaelis–Menten kinetics with a correction for multiple substrate competition, indicating a significant decrease in TRP influx into the central nervous system under Moja-De. ATD Moja-De decreased TRP influx into the brain and central nervous system 5-HT synthesis safely and effectively and was well tolerated, allowing it to be used in children and adolescents. Future research into other secondary, compensatory effects induced by ATD in patients with neuropsychiatric disorders and healthy populations is needed. ATD Moja-De allows this type of research with a focus on a developmental viewpoint.Electronic supplementary materialThe online version of this article (doi:10.1007/s00702-012-0793-z) contains supplementary material, which is available to authorized users.

Molecular Evolution of Plant AAP and LHT Amino Acid Transporters.

Nitrogen is an essential mineral nutrient and it is often transported within living organisms in its reduced form, as amino acids. Transport of amino acids across cellular membranes requires proteins, and here we report the phylogenetic analysis across taxa of two amino acid transporter families, the amino acid permeases (AAPs) and the lysine–histidine-like transporters (LHTs). We found that the two transporter families form two distinct groups in plants supporting the concept that both are essential. AAP transporters seem to be restricted to land plants. They were found in Selaginella moellendorffii and Physcomitrella patens but not in Chlorophyte, Charophyte, or Rhodophyte algae. AAPs were strongly represented in vascular plants, consistent with their major function in phloem (vascular tissue) loading of amino acids for sink nitrogen supply. LHTs on the other hand appeared prior to land plants. LHTs were not found in chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean alga Klebsormidium flaccidum encodes KfLHT13 and phylogenetic analysis indicates that it is basal to land plant LHTs. This is consistent with the hypothesis that characean algae are ancestral to land plants. LHTs were also found in both S. moellendorffii and P. patens as well as in monocots and eudicots. To date, AAPs and LHTs have mainly been characterized in Arabidopsis (eudicots) and these studies provide clues to the functions of the newly identified homologs.

Nutrition and chronic kidney disease

The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis

ObjectiveTo evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage.MethodsTwenty-eight normotensive...

Liver‐specific‐aquaporin 11 knockout mice show rough endoplasmic reticulum dilation and vacuole formation in periportal hepatocytes in response to fasting and re‐feeding with regular chow or protein, and following oral amino acid load

Aquaporin 11 (AQP11) is a channel protein with unknown physiological function expressed in multiple organs. It has previously been shown that global AQP11 KO mice die early due to malfunction of the kidney caused by vacuolization of proximal tubule (Morishita et al., 2005). Here we report generation of liver-specific-AQP11 KO mice to study AQP11 function in the liver of mice with undisturbed kidney function. Microscopic analyses revealed that the liver in unstressed liver-specific-AQP11 KO mice shows no vacuolization. Fasting of the mice for 24 hours leads to slight dilatation of rough endoplasmic reticulum (RER) in the periportal hepatocytes. Re-feeding of the mice with regular mouse chow induces rapid generation of large vacuoles in the periportal hepatocytes. The same effect is obtained by oral administration of a protein or larger doses of different amino acids (Glu, Gln, Gly, Ala), while administration of glucose or triglyceride does not induce vacuolization. Only a sub-population of hepatocytes isolated from liver-specific-AQP11 KO mice develops vacuoles in vitro when cultured in medium supplemented with 20 mM glutamine. We propose that vacuolization of RER is a result of accumulation of a product(s) of amino acid metabolism inside the RER lumen and osmotic swelling of this compartment. The study was supported by Lundbeck Foundation.

P03-130 - Effects of a diminished serotonin synthesis on memory and impulsive aggression in adult ADHD

IntroductionNumerous results from investigations including children with ADHD show associations between a diminished serotonin synthesis and memory impairments as well as higher aggression scores. The aim of the present study was the investigation of the association between a diminished serotonin synthesis, logical memory and impulsive aggression in male adult patients with ADHD.MethodTwenty male adult patients with ADHD and twenty healthy controls were recruited for this double-blind within subjects crossover study. Subjects completed the Rapid Tryptophan Depletion (RTD) Test or a placebo condition (balanced amino acid load) on either one of two examination days. Clinical variables and general intellectual functioning were assessed. The neuropsychological test battery included the subtest logical memory from the Wechsler Memory Scale (WMS-R), self-assessment of aggression as well as the Point Subtraction Aggression Game (PSAG).ResultsStatistical analysis revealed significant memory impairments of ADHD patients, which were associated with severity of symptoms in early childhood as well as subjective aggression scores. Effects of the tryptophan depletion were not found, neither for the logical memory subtest nor performance in the PSAG.ConclusionsIn contrast to previous studies, these findings suggest that the serotonergic system as reflected by the RTD Test has no effect on memory performance or impulsive aggression. However, these results may be due to possible interactions of other catecholamine systems with the serotonergic system that were not controlled in this study. Therefore an additional study is needed to further explore the catecholamine systems and their effects on memory and impulsive aggression.

Effect of an intrajugular load of glucose or amino acid or their mix on cow milk yield and composition

During the first stage of lactation of dairy cows the flux of nutrients is under an homeoretic control, which modifies the metabolism of body tissues and gives the priority of their utilisation to the mammary gland (Bauman and Currie, 1980). Nevertheless, while it is clear that the homeoretic control is not simply due to a lack of nutrients, it is not clear yet if this lack is the limit for mammary gland syntheses and which among nutrients is the more limiting, and if a larger nutrient availability could allows a higher yielding (Knight et al., 1994). Aim of our research was to study the milk yield and its composition changes as well as those of some blood metabolites and hormones, in dairy cows of low-average genetic merit,........

Early Nutrient Supply and the Preterm Infant

Early Nutrient Supply and the Preterm Infant

Increased phloem transport of S-methylmethionine positively affects sulfur and nitrogen metabolism and seed development in pea plants.

Seeds of grain legumes are important energy and food sources for humans and animals. However, the yield and quality of legume seeds are limited by the amount of sulfur (S) partitioned to the seeds. The amino acid S-methylmethionine (SMM), a methionine derivative, has been proposed to be an important long-distance transport form of reduced S, and we analyzed whether SMM phloem loading and source-sink translocation are important for the metabolism and growth of pea (Pisum sativum) plants. Transgenic plants were produced in which the expression of a yeast SMM transporter, S-Methylmethionine Permease1 (MMP1, YLL061W), was targeted to the phloem and seeds. Phloem exudate analysis showed that concentrations of SMM are elevated in MMP1 plants, suggesting increased phloem loading. Furthermore, expression studies of genes involved in S transport and metabolism in source organs, as well as xylem sap analyses, support that S uptake and assimilation are positively affected in MMP1 roots. Concomitantly, nitrogen (N) assimilation in root and leaf and xylem amino acid profiles were changed, resulting in increased phloem loading of amino acids. When investigating the effects of increased S and N phloem transport on seed metabolism, we found that protein levels were improved in MMP1 seeds. In addition, changes in SMM phloem loading affected plant growth and seed number, leading to an overall increase in seed S, N, and protein content in MMP1 plants. Together, these results suggest that phloem loading and source-sink partitioning of SMM are important for plant S and N metabolism and transport as well as seed set.

Postprandial Cysteine/Cystine Redox Potential in Human Plasma Varies with Meal Content of Sulfur Amino Acids1–

Few data are available on plasma redox responses to sulfur amino acid (SAA) loads. In this study, we had 2 aims: to determine whether the SAA content of a meal affected postprandial plasma cysteine (Cys), cystine (CySS), or redox potential (EhCySS) in humans and whether SAA intake level (adequate or inadequate) in the days preceding the meal challenge affected these postprandial levels. Eight healthy individuals aged 18–36 y were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (inadequate SAA) and then fed isoenergetic, isonitrogenous meals with adequate SAA for 5 d. On the first and last days with the chemically defined meals, a morning meal containing 60% of the daily food intake was given, and plasma Cys, CySS, and EhCySS were determined over an 8-h postprandial time course. Following equilibration to adequate intake, provision of the meal with SAA resulted in increased plasma Cys and CySS concentrations and more reduced plasma EhCySS compared with the postprandial values following the same meal without SAA. Equilibration to inadequate SAA intake for the days preceding the meal challenge did not affect this response. The magnitude of the difference in postprandial plasma EhCySS (10 mV) due to meal content of SAA was comparable to those which alter physiologic signaling and/or are associated with disease risk. Consequently, the SAA content of meals could affect physiologic signaling and associated disease mechanisms in the postprandial period by changes in Cys, CySS, or EhCySS.

Limitations of Owl Reproduction in the Wild: is there a Role for Food Quality Besides Quantity?

Avian studies have shown that food quality (amino acid load) can act as a limiting factor in reproduction and possibly breeding density. In owls, the role of food quality may have been largely overlooked due to the strong effect of food quantity. I examined evidence of food quality limitation in owl reproduction from four sets of data: (1) population data in Tawny Owls and diurnal birds of prey in a degenerate forest, (2) post-laying breast muscle conditions of Tawny Owls Strix aluco and Sparrowhawks Accipiter nisus which strongly relied on internal amino acid stores during egg formation, (3) amino acid deficiency-related embryo anomaly data in failed eggs of Barn Owls Tyto alba, Little Owls Athene noctua, and two reference species, and (4) growth of Tawny Owl chicks experimentally fed with day-old chickens or mice. The Tawny Owl population was found to be stable whereas sympatric bird of prey species greatly declined; breeding female Tawny Owls (n = 5) did not show a decline of breast muscle tissue as was found in Sparrowhawks. Embryo mortality from amino acid deficiency was estimated at 63% and 12% in Barn Owls and Little Owls, respectively. Growth rate of Tawny Owl chicks did not relate to food type. I conclude that egg amino acid investments can affect embryo viability in owls, but mainly in relation to reproductive strategy instead of environment. I hypothesize that owls can obtain additional amino acids from their caecal bacteria, which are lacking in birds of prey, and thereby are less dependent on amino acid availability in the food chain to acquire the amino acids needed for egg formation and chick growth.

An Amino Acid Model for Latent Fingerprints on Porous Surfaces*

Analytical standards are needed in latent fingerprint detection for research and development as well as for quality control in routine work because normal fingerprints are too varied for comparison studies and tests. One way is to create latent fingerprints. For the amino acid sensitive detection method this can be achieved by coating test items with an amino acid solution using a modified commercial office bubble jet printer. Besides low costs, fast and easy preparation, the main advantage of a bubble jet printer is that the amino acid loading per area on the test item can be calculated by weighing the cartridge on a balance. This opens the possibility to determine the deviation for every printing series. The reproducibility of prints in a printing series made by one cartridge has a deviation of 2-16% and of prints made by different cartridges 20-25%.

Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs

Background: Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven.Objective: We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient.Design: Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [14C]leucine infusion.Results: Net hepatic glucose uptake in the PoAA condition was ≤50% of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [14C]leucine utilization were ≈2-fold greater (P < 0.05) and albumin synthesis was 30% greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition.Conclusions: Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling.

Phenylalanine Requirement, Imbalance, and Dietary Excess in One-Week-Old Chicks: Growth and Phenylalanine Hydroxylase Activity

Two experiments were performed to study Phe imbalance and toxicity in 1-wk-old Babcock B380 chicks resulting from the addition of either a mixture of indispensable amino acids lacking Phe (IAA - Phe) or excess Phe to a diet that was nutritionally adequate in Phe. Chicks received a preexperimental semipurified diet for 1 wk and experimental diets from 7 to 14 d of age. In the first experiment, the chicks were given diets with Phe levels at 0.24, 0.29, 0.34, 0.39, 0.44, and 0.49% of the diet to determine the Phe requirement. The requirement of the chicks for Phe, based on weight gain and feed efficiency, was determined to be 0.39% of the diet. In experiment 2, the IAA - Phe (10% of the diet) or excess Phe (2% of the diet) was added to a diet containing 0.44% Phe. Chicks given the IAA - Phe or excess Phe had significantly slower growth rates than chicks given the basal diet (P > or = 0.05). The activities of the major hepatic enzyme of Phe catabolism, Phe hydroxylase (PAH), were significantly higher than that of chicks fed the basal diet when the chicks were fed the diets containing IAA - Phe plus 1.1% Phe (P > or = 0.05) but not when chicks were fed the diet containing IAA - Phe alone. The activity of PAH in chicks given the excess (2%) Phe was nearly 4 times the activity of PAH in chicks given the basal diet. Adding IAA - Phe to the diet containing excess Phe also resulted in higher PAH activity than was observed in chicks fed the basal diet, although the activity was significantly lower than observed for chicks receiving the diet containing excess Phe alone (P > or = 0.05). It is concluded that hepatic PAH activity in chicks increases primarily in response to its substrate, Phe. A dietary amino acid load without Phe reduces this response to excess Phe.

Could lipid infusion be a risk for parenteral nutrition-associated cholestasis in low birth weight neonates?

To assess whether lipid infusion could be a risk factor for parenteral nutrition-associated cholestasis (PNAC) in low birth weight neonates, 22 newborns with cholestasis (29.8 +/- 1.6 weeks, 1298 +/- 217 g) were compared with 22 without cholestasis (29.5 +/- 1.7 weeks, 1286 +/- 363 g). The mean level of peak direct bilirubin for the cholestasis group was 4.6 mg/dl compared to 1.2 mg/dl for the noncholestasis group. A univariate analysis revealed that PNAC was significantly related to duration of fasting (p = 0.008) and parenteral nutrition (p < 0.0001), days of antibiotics use (p = 0.025), positive C-reactive protein (p = 0.018) or gastric culture (p = 0.018), and feeding intolerance (p < 0.0001). Total amino acid amount (p < 0.0001), total lipid amount (p < 0.0001), and average daily lipid amount (p = 0.002) were significantly higher in the cholestasis group than in the noncholestasis group. Conversely, prenatal administration of dexamethasone was a significant protective factor of PNAC (p = 0.008). Logistic regression analysis revealed that the cumulative amount of lipid infusion was an independent risk factor for PNAC (p = 0.041; OR 1.174; CI 1.007-1.369). We suggest that decreasing the cumulative load of amino acids and intralipids with early trophic feeding, control of infection, and prenatal administration of dexamethasone could possibly attenuate the severity of PNAC.

Amino acid transporter expression and localisation studies in pea (Pisum sativum).

Expression of the amino acid permeases PsAAP1 and PsAAP2 was analysed in developing pea (Pisum sativum L.) plants. Both transporters were expressed in seed coats and cotyledon epidermal transfer cells and storage parenchyma cells. AAP expression is developmentally regulated and coincides with the onset of storage protein synthesis. Nitrogen was shown to induce AAP expression and AAP transcript levels were upregulated during the photoperiod. Analysis of Arabidopsis thaliana AAP1 promoter activity in pea, using promoter-β-glucuronidase (promotor-GUS) studies, revealed targeting of GUS to seed coats and cotyledon epidermal transfer cells. Expression was found in the nutritious endosperm during the early stages of seed development, whereas GUS staining in embryos was detected from the heart stage onward. In addition, AAP1 expression was observed in the phloem throughout the plant. This finding equally applied to PsAAP1 expression as shown by in situ mRNA hybridisation, which also demonstrated that PsAAP1 expression was localised to companion cells. Overall, PsAAP1 expression patterns and cellular localisation point to a function of the transporter in phloem loading of amino acids for translocation to sinks and in seed loading for development and storage protein accumulation.

PEPT1 Enhances the Uptake of Gabapentin via Trans-Stimulation of b0,+ Exchange

The aims of this study were (1) to determine whether amino acid and dipeptide loading can improve the effective permeability of gabapentin and (2) to characterize the underlying mechanism that is responsible for this interaction. An in situ single-pass rat intestinal perfusion model was used to assess the effective permeability of gabapentin in rat, in the absence and presence of cellular loading by amino acid and dipeptide mixtures. Compared to gabapentin alone, cellular loading with amino acid and dipeptide mixtures significantly improved the effective permeability of gabapentin by 46-79% in jejunum and by 67-72% in ileum (p < or = 0.01). However, coperfusion of glycylsarcosine (i.e., PEPT1 substrate), methionine sulfoximine (i.e., glutamine synthase inhibitor), or lysine and arginine (i.e., b(0,+) substrates) with the amino acid and dipeptide mixtures compromised the intestinal uptake of gabapentin. These findings demonstrate, for the first time, a direct relationship between the PEPT1-mediated uptake of a dipeptide and the trans-stimulated uptake of gabapentin (an amino acid-like drug) through the transport system b(0,+).

Advanced Glycation End Products and Nephrotoxicity of High-Protein Diets

The popularity of high-protein diets has surged recently as obesity has become more and more common in the United States and other developed nations. In view of the high prevalence of type 2 diabetes and chronic kidney disease among obese people, it is important to understand potential effects of high-protein diets on the kidney. The hypothesis that high-protein diets are nephrotoxic because of their excessive dietary advanced glycation end product (AGE) content and an increased amino acid load that enhances AGE formation in situ was explored. This review discusses the following evidence: (1) High-protein diets are deleterious to the kidney; (2) AGE are metabolic mediators of kidney damage; (3) dietary protein-derived AGE contribute to proinflammatory and pro-oxidative processes in diabetes and kidney disease; and (4) dietary protein-derived AGE produce functional and structural abnormalities that are involved in kidney damage. Future research should consider dietary AGE as a potential therapeutic target for kidney disease in obesity, diabetes, and perhaps other causes of chronic kidney disease.