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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.

Amino Acids, Branched-Chain↗

Protein synthesis in rat liver: influence of amino acids in diet on microsomes and polysomes.

Rats were killed 1 hour after having been fed by stomach tube with amino acid mixtures that were either nutritionally complete or lacked tryptophan. Microsomes isolated from the livers of animals fed the incomplete mixture showed a reduced capacity to incorporate (14)C-leucine in vitro, and polysomes prepared from the same livers showed an increased proportion of monosomes and disomes. Prior treatment with actinomycin D did not prevent these differences in response to the two amino acid mixtures, an indication that synthesis of messenger RNA may not be involved in the cell mechanism which recognizes differences in amino acid pattern.

Amino Acids↗

Effects of tryptophan depletion on Poggendorff illusion, corner Poggendorff illusion, and attention.

The effects of a tryptophan-free amino acid mixture on Poggendorff illusion, corner Poggendorff illusion, and attention were investigated with 12 male subjects who ingested either a balanced amino acid mixture or a tryptophan-free mixture, the latter known to cause a marked depletion of brain tryptophan and serotonin. No significant difference between the two mixtures on the perceptual illusions was found.

Adult↗

Augmented thermic effect of amino acids under general anaesthesia occurs predominantly in extra-splanchnic tissues.

1. Intravenous infusion of amino acid mixtures stimulates human oxidative heat production more effectively under general anaesthesia than in the unanaesthetized state. To analyse the splanchnic and extra-splanchnic regional distribution of this stimulation, whole body and splanchnic oxygen uptake, blood flow and blood temperatures were measured by a catheterization technique in 14 patients undergoing isoflurane anaesthesia for abdominal surgery. During the anaesthesia period, a mixture of 19 amino acids (240 kJ/h) was infused intravenously into seven of the patients while the others served as controls, receiving isovolumic infusions of a nutrient-free saline solution. 2. Whole body oxygen consumption fell by approximately 40% during anaesthesia and surgery in the controls. Approximately 80-95% of the reduction occurred in the extra-splanchnic tissues. The splanchnic oxygen uptake fell by 31 +/- 6% in the controls during the initial phase of anaesthesia, after which it returned to the pre-anaesthesia level. The initial reduction of the controls' splanchnic oxygen consumption accounted for only approximately 23% of the simultaneous anaesthesia-induced reduction in pulmonary oxygen uptake. No initial reduction of the splanchnic oxygen uptake was observed in the patients treated with amino acid. 3. The amino acid infusion stimulated the whole body oxidative heat production by approximately 18 W during anaesthesia and surgery and by approximately 70 W at the emergence from anaesthesia. Approximately 74% of the stimulation occurred in the extra-splanchnic tissues. At awakening, the splanchnic oxygen uptake rose to approximately 64% above the pre-anaesthesia level in the amino acid group. 4. During the entire period of anaesthesia, the whole body heat content fell by 282 +/- 68 kJ in the controls and by 57 +/- 25 kJ in the amino acid group. Amino acid treatment thus prevented approximately 80% of the anaesthesia-induced reduction in whole body heat content. 5. During anaesthesia and surgery, cardiac output was approximately 25% and approximately 16% below the baseline, preanaesthesia levels in the control and amino acid groups, respectively. At awakening, it rose to approximately 44% above baseline in the amino acid group while in the controls it remained unchanged. In both groups the splanchnic blood flow was unaffected by anaesthesia or by amino acid infusions.

Amino Acids↗

Intravenous mixed amino acids and fats do not stimulate exocrine pancreatic secretion.

We compared the responses of the canine exocrine pancreas to intraduodenal versus intravenous administration of mixed amino acids, fat emulsion, and glucose. Graded doses of amino acid mixture and of fat emulsion gave graded responses in volume, protein, and bicarbonate when administered intraduodenally. In contrast, the same doses of the amino acid mixture and fat emulsion administered by central intravenous infusion caused no significant pancreatic secretion of volume, protein, or bicarbonate. Graded doses of glucose caused no statistically significant pancreatic secretion whether they were given intraduodenally or intravenously. We conclude, contrary to a previously published observation, that amino acids and fats given parenterally do not stimulate pancreatic secretion. As a corollary, it is reasonable to assume that the pancreas is not stimulated during total parenteral nutrition with acute pancreatitis or a pancreatic fistula.

Amino Acids↗

Amino acid supplementation affects hematological and biochemical parameters in elite rugby players.

Individual amino acid supplementation affects various types of athletic performance. However, little information on combinations of amino acids is currently available. This study evaluated an amino acid mixture containing L-leucine, L-isoleucine, L-valine, L-arginine, and L-glutamine to 3.6 g of total amino acids per dose. Twenty-three rugby players were given 3.6 g, twice, daily of the amino acid mixture for 90 days (June-August 1994) and blood samples were collected for analyses in September 1993, March 1994, September 1994, and September 1995. After 90 days of supplementation, almost all of the athletes reported improvement in vigor and earlier recovery from fatigue. Significant increases (P<0.05) were observed in hemoglobin, RBC count, hematocrit, and serum iron by amino acid supplementation. Significant increases (P<0.05) were also noted in total cholesterol and low-density lipoprotein along with decreased (P<0.05) alkaline phosphatase. All values reverted to original levels when measured after one year of continued training without supplementation.

Adult↗

An increase in strength of tilt aftereffect associated with tryptophan depletion.

The effects of a tryptophan-free amino acid mixture on tilt aftereffect, movement aftereffect, and the Mueller-Lyer illusion were studied. 12 male subjects ingested either a balanced amino acid mixture or a tryptophan-free mixture which causes a marked depletion of brain tryptophan and serotonin. The tryptophan-free mixture significantly increased the strength of tilt aftereffect but had no effect on movement aftereffect or the Mueller-Lyer illusion. These results were discussed with reference to the pharmacological activity of serotonin and its influence on the strength of lateral inhibition in mammalian brains.

Adult↗

Identification and activity-dependent labeling of peripheral sensory structures on a spionid polychaete.

In marine sedimentary habitats, chemoreception is thought to coordinate feeding in many deposit-feeding invertebrates such as polychaetes, snails, and clams. Relatively little is known, however, about the chemosensory structures and mechanism of signal transduction in deposit feeders. Using electron microscopy, confocal laser scanning microscopy (CLSM), and immunohistochemistry, we investigated the structure and function of putative chemosensory cells on the feeding appendages of a deposit-feeding polychaete species, Dipolydora quadrilobata. Tufts of putative sensory cilia were distributed over the prostomium and feeding palps and typically occurred next to pores. Examination of these regions with transmission electron microscopy revealed multiciliated cells with adjacent glandular cells beneath the pores. The sensory cells of prostomium and palps were similar, displaying an abundance of apical mitochondria and relatively short ciliary rootlets. Staining with antiserum against acetylated alpha-tubulin was examined by CLSM, and revealed axonal processes from putative sensory tufts on the palp surface to palp nerves, as well as many free nerve endings. Activity-dependent cell labeling experiments were used to test the sensitivity of putative sensory cells on the palps to an amino acid mixture that elicited feeding in previous behavioral experiments. In static exposures, the number of lateral and abfrontal cells labeled in response to the amino acid mixture was significantly greater than in the controls. Ultrastructural, positional, and now physiological evidence strongly suggests that spionid feeding palps are equipped with sensory cells, at least some of which function as chemoreceptors.

Amino Acids↗

The effect of raising or lowering tryptophan levels on aggression in vervet monkeys.

Social groups of vervet monkeys (Cercopithecus aethiops) were given amino acid mixtures that were tryptophan-free (T-), nutritionally balanced (B), or contained excess tryptophan (T+). The T- mixture caused a marked decrease in plasma tryptophan and the T+ mixture a large increase. Behavioral observations were made on the animals after administration of the amino acid mixtures both during spontaneous activity and while the (fasted) animals were competing for food newly placed in the feeder. The only effect of the biochemical manipulations on spontaneous aggression was an increase in aggression of the male animals with the T- mixture. During competition for the food the T- mixture increased and the T+ mixture decreased aggression in the males, while the T+ mixture decreased aggression in females. These data indicate that brain 5-hydroxytryptamine can influence aggression in a primate and suggest that altered tryptophan levels can influence aggression more reliably at higher levels of arousal.

Aggression↗

Rapid suppression of protein degradation in skeletal muscle after oral feeding of leucine in rats.

A diet containing adequate amounts of protein rapidly suppresses myofibrillar protein degradation in rats and mice. This study determined whether dietary amino acids inhibit postprandial protein degradation in rat skeletal muscle. When rats fed on a 20% casein diet for 1 h after 18 h starvation, the rate of myofibrillar protein degradation measured by N(tau)-methylhistidine release from the isolated extensor digitorum longus muscle was significantly (p < 0.05) decreased at 4 h after refeeding. A diet containing an amino acid mixture which is the same composition as casein also reduced myofibrillar protein degradation at 4 h after refeeding (p < 0.05). An essential amino acid mixture (15.1%, corresponding to casein composition) and a leucine (2.9%) diets reduced the rate of myofibrillar protein degradation after refeeding (p < 0.05), whereas a protein free diet did not. Administration of leucine alone (0.135 g/100 g body weight) by a feeding tube induced a decrease in the rate of myofibrillar protein degradation at 2 h after administration (p < 0.05), whereas the serum insulin concentration was constant after leucine administration. These results suggested that leucine is one of regulating factors of myofibrillar protein degradation after refeeding of a protein diet.

Journal Article↗

Threonine requirement of the broiler chick as affected by protein level and source.

The threonine requirement of the young broiler chick was estimated in two experiments. In Experiment 1, a threonine-deficient corn-peanut meal-amino acid mixture was included in a basal diet at levels equivalent to 15 and 20% crude protein. In Experiment 2, a purified crystalline amino acid mixture, also limiting in threonine, was included in a basal diet at levels equivalent to 10.98 and 18.3% crude protein. When expressed as a percent of diet, the estimated threonine requirements increased as dietary protein content increased. However, when expressed as a percent of dietary protein, the estimated threonine requirements were not significantly affected by dietary protein content, and were similar for the two experiments. It was concluded that the threonine requirement is 3.7% of dietary crude protein, and is little affected by dietary protein content.

Animals↗

Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis.

We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients), or isocaloric glucose (33 patients) for a maximum of 16 days. The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose. The patients took part in the study for 5-6 days. In each group 17 patients woke up. In the amino acid group eleven died and four developed renal failure. In the glucose group ten died, three developed renal and two respiratory failure, and one remained encephalopathic. The coma score worsened in three of the patients who died in the amino acid group, but in all patients who died in the glucose group. The negative nitrogen balance on entry reversed in the amino acid group, but not in the glucose group. Thus, the branched chain enriched amino acid supplement did not change the prognosis for wake-up, but had other effects on the cerebral state and on nitrogen homeostasis.

Adult↗

Responses in milk constituents to intravascular administration of two mixtures of amino acids to dairy cows.

Four Holstein-Friesian cows were used to investigate the effects of intravascular infusions of AA mixtures on milk constituents. Cows were in wk 11 to 28 of lactation and were fed a basal concentrate (142 g of CP/kg of DM) and grass silage (149 g of CP/kg of DM) in a 60:40 ratio (percentage of DM). Cows were fed hourly, and feed intake was fixed at 95% of ad libitum intake for each experimental period. Each cow received a 4-d jugular saline infusion, followed by a 5-d jugular infusion of a mixture of AA. Two mixtures of AA were used in a crossover design. The first mixture contained both the essential AA and non-essential AA found in milk protein (total AA); this mixture was infused at 400 g of AA/d. The other mixture represented the essential AA fraction only and was infused at 208 g/d. Infusion of total AA increased milk protein concentration from 32.4 to 35.0 g/kg, and essential AA increased milk protein concentration from 32.5 to 36.9 g/kg; milk protein yield increased by 87 g/d (total AA) and 143 g/d (essential AA). Intravascular administration of AA specifically stimulated milk protein concentration, and the efficiency with which the AA were used was higher than had been previously reported when AA supply was increased either by dietary supplementation or by abomasal infusion.

Amino Acids↗

Effects of voluntary wheel running and amino acid supplementation on skeletal muscle of mice.

The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by endurance training in hindlimb (gastrocnemius, tibialis, soleus) and respiratory (diaphragm) muscles of mice. Male C57Bl6 mice were divided in four groups: control sedentary, sedentary supplemented with amino acid mixture (BigOne, 1.5 mg g day(-1) in drinking water for 8 weeks), running (free access to running wheels for 8 weeks), and running supplemented with amino acid mixture. Myosin heavy chain (MHC) isoform distribution was determined in all muscles considered. Fiber cross-sectional area (CSA) was measured in the soleus muscle. In all muscles except the tibialis, endurance training was associated with an overall shift towards the expression of slower MHC isoforms. Amino acid supplementation produced a shift towards the expression of faster MHC isoforms in the soleus and diaphragm muscles, and partially antagonized the effects of training. Immunohistochemical analysis of CSA of individual muscle fibers from the soleus muscle suggests that voluntary running produced a decrease in the size of type 1 fibers, and amino acid supplementation during training resulted in an increase in size in both type 1 and type 2A fibers. Collectively, these results suggest that the endurance adaptations induced by voluntary running depend on the muscle type, and that amino acid supplementation is able to modulate both fiber size and MHC isoform composition of skeletal muscles in sedentary and exercised mice.

Adaptation, Physiological↗

Intragastric bolus feeding of meals containing elementary, partially hydrolyzed or intact protein causes comparable changes in interorgan substrate flux in the pig.

Dietary protein given as pre-digested protein improves the nutritional value of the meal. However, studies measuring absorption kinetics of pre-digested protein or free amino acid mixtures are scarce and suffer from methodological problems. Therefore, the study was designed to study whether differences in absorption kinetics play a role. The kinetics of substrate production or consumption after a rapid gastrically-infused meal was studied across the portal drained viscera, liver and hindquarter in conscious, multicatheterized healthy pigs of 20-22 kg (n = 12). The meal contained carbohydrates and protein (1.44 g/kg body weight) as intact whey protein isolate, moderately-hydrolyzed protein digest or equivalent amino acid mixture (including glutamine and asparagine). For almost all amino acids and glucose, intestinal production, liver and hindquarter uptake were similar. The higher liver urea production (less than 15% of total alpha-amino intake) after the meals with pre-digested protein or free amino acids was related to the marginally higher intestinal glutamine breakdown (not significant) and ammonia production. Our results suggest that in the normal healthy pig, uptake and metabolism of moderately hydrolyzed,free amino acid or intact protein meals with identical composition is not different.

Journal Article↗

Effects of concentration on in vivo absorption of a peptide containing protein hydrolysate.

Amino acid absorption from a peptide-containing protein hydrolysate and an equivalent amino acid mixture over a range of concentrations of the two--such as is thought to be found in the normal intestine after a meal--has been studied using a jejunal perfusion technique in man. The relative rates of amino acid absorption from the protein hydrolysate and amino acid mixture varied markedly with concentration, demonstrating that the global hypothesis that peptides confer an advantage in amino acid absorption in vivo is too simple. There is a highly significant correlation between amino acid absorption and the concentrations of amino acid in the perfusate, whether this contained amino acid or protein hydrolysate, suggesting that, under these experimental conditions at least, the presence of distinct amino acid and peptide transport systems is relatively unimportant. Doubt is thus cast upon suggestions derived from previous intestinal perfusion experiments that intact peptide transport may be nutritionally significant in man.

Adult↗

Effects of amino acid balance and energy:protein ratio on energy and nitrogen metabolism in male broiler chickens.

1. An experiment was performed with growing broiler chickens (14 to 21 d old) to examine 3 diet characteristics which have been implicated in regulatory elevation of metabolic rate: an imbalanced amino acid mixture, high dietary energy concentration and low protein concentration. 2. Differences in energy expenditure could be explained almost entirely (93%) by differences in quantities, and therefore costs, of protein and fat accretion. There was no indication of regulatory diet-induced thermogenesis. Heat production was not significantly correlated with CP:TME ratio and was negatively correlated (P < 0.01) with dietary TME concentration. 3. Heat production was closely correlated (P < 0.001) with rate of protein accretion, which in turn was more strongly associated with intake of the first-limiting amino acid (lysine) than with total protein intake. Heat production on an imbalanced, lysine-limited, amino acid mixture was no greater than on a balanced amino acid source with the same lysine concentration. 4. There was no indication of a stimulation of heat production by excess amino acids. Heat production, adjusted for body weight by covariance analysis, was similar on paired diets which had identical lysine concentrations but a 1.5- or 2-fold difference in crude protein concentration. 5. There was a strong negative correlation (P < 0.001) between protein retention per g of lysine consumed and lysine: CP ratio, suggesting that, in this case, response to a limiting amino acid was improved by the presence of a super-abundance of other amino acids.

Adipose Tissue↗

Trigonelline, a naturally occurring constituent of green coffee beans behind the mutagenic activity of roasted coffee?

Trigonelline and amino acids are natural components in green coffee beans. Model systems mimicking coffee roasting were used to produce heated samples of trigonelline, amino acids and glucose. Trigonelline and amino acids were heated separately or in combinations for 20 min at 250 degrees C. The results of bacteria mutation assays (Salmonella typhimurium strains TA 98, YG 1024 and YG 1029) showed that trigonelline, alone or in combination with most of the single amino acids and mixtures of amino acids, yielded potent mutagenic activity. Of the singly heated compounds, the highest mutagenic activity was found for trigonelline. The mutagenic activity detected with metabolic activation of the heated trigonelline samples indicated that the mutagenic compounds might be amines; however, higher mutagenic activity was found for trigonelline and its combinations without metabolic activation, which suggests that other types of mutagens (direct-acting) were predominant. High-performance liquid chromatographic analysis of some of the heated samples did not reveal the presence of any known mutagenic heterocyclic amine.

Alkaloids↗