Diet and uptake of aldomet by the brain: competition with natural large neutral amino acids

Science ◽  
1977 ◽  
Vol 197 (4307) ◽  
pp. 1014-1015 ◽  
Author(s):  
D. Markovitz ◽  
J. Fernstrom
1975 ◽  
Vol 229 (1) ◽  
pp. 229-234 ◽  
Author(s):  
J Lutz ◽  
JK Tews ◽  
AE Harper

Histidine concentration in the brain decreases rapidly when rats are fed a low protein diet in which an amino acid imbalance is created by addition of an amino acid mixture devoid of histidine. Competition for histidine transport into the brain was suggested as an explanation for this effect. Therefore, animo acid mixtures simulating composition of plasma from rats fed basal or histidine-imbalanced diets were added to media to evaluate their effects on uptake of histidine by brain slices during a 60-min incubation period. At the concentrations actually found in plasma, the unbalanced mixture decreased histidine uptake significantly more than did the basal mixture. Two distinct inhibition patterns were observed with different groups of amino acids: a linear decrease in histidine uptake with a mixture of the small neutral, hydroxyl, basic, and acidic amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids. Inhibition of histidine transport by the complete mixtures reflected these two effects. Plasma patterns and concentrations of competitive amino acids as well as the concentration of histidine appear to be factors involved in decreasing histidine transport into the brain.


1988 ◽  
Vol 66 (5) ◽  
pp. 683-688 ◽  
Author(s):  
Karen L. Teff ◽  
Simon N. Young

We compared the acute effects of intragastric administration of protein and carbohydrate on tryptophan and 5-hydroxytryptamine (5HT) in rat brain, pineal, intestine, and pancreas. Protein decreased and carbohydrate increased brain indoles relative to water-infused controls. These effects were due to competition between the large neutral amino acids for entry into the brain. This competition does not exist in the pineal. The macronutrients had no effect on pineal tryptophan metabolism. In the intestine, protein resulted in higher tryptophan levels as compared to controls, owing to absorption of tryptophan in the protein. However intestinal 5HT levels were influenced by factors other than precursor availability. Pancreatic indoles were affected in a similar manner to the brain indoles. Competition between the large neutral amino acids for entry into the pancreas was also indicated by the finding that valine administration lowered brain and pancreatic tryptophan, but not the levels in the intestine and pineal. It remains to be seen whether the decrease in pancreatic 5HT after a protein meal and the increase after carbohydrate modulate the release of insulin and glucagon.


1976 ◽  
Vol 160 (3) ◽  
pp. 589-595 ◽  
Author(s):  
J D Fernstrom ◽  
M J Hirsch ◽  
D V Faller

Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation. Sera from animals fed carbohydrate plus fat contained 2.5 times as much free tryptophan concentrations did not differ. Similarly, sera from rats fed on carbohydrate, large neutral amino acids, and 40% fat contained 5 times as much free tryptophan as those from rats given this meal without fat, but brain tryptophan concentrations increased by only 26%. Correlations were made between brain tryptophan and (1) free serum tryptophan, (2) the ratio of free serum tryptophan to the sum of the other large neutral amino acids in serum that compete with it for uptake into the brain, (3) total serum tryptophan or (4) the ratio of total serum tryptophan to the sum of its circulating competitors. The r values for correlations (3) and (4) (i.e. those involving total serum tryptophan) were appreciably higher than those for correlations (1) and (2). Brain tyrosine concentrations also were found to correlate well with the ratio of serum tyrosine to the sum of its competitors. Competition for uptake into the brain among large neutral amino acids (represented here by serum ratios) thus appears to determine the changes in the brain concentrations of these amino acids under physiological conditions(i.e. after food consumption). Total, not free, serum tryptophan is the relevant index for predicting brain tryptophan concentrations.


1983 ◽  
Vol 245 (4) ◽  
pp. R556-R563 ◽  
Author(s):  
J. K. Tews ◽  
A. E. Harper

Transport of histidine, valine, or lysine into rat brain slices and across the blood-brain barrier (BBB) was determined in the presence of atypical nonprotein amino acids. Competitors of histidine and valine transport in slices were large neutral amino acids including norleucine, norvaline, alpha-aminooctanoate, beta-methylphenylalanine, and alpha-aminophenylacetate. Less effective were aromatic amino acids with ring substituents; ineffective were basic amino acids and omega-amino isomers of norleucine and aminooctanoate. Lysine transport was moderately depressed by homoarginine or ornithine plus arginine; large neutral amino acids were also similarly inhibitory. Histidine or valine transport across the BBB was also strongly inhibited by large neutral amino acids that were the most effective competitors in the slices (norvaline, norleucine, alpha-aminooctanoate, and alpha-aminophenylacetate); homoarginine and 8-aminooctanoate were ineffective. Homoarginine, ornithine, and arginine almost completely blocked lysine transport, but the large neutral amino acids were barely inhibitory. When rats were fed a single meal containing individual atypical large neutral amino acids or homoarginine, brain pools of certain large neutral amino acids or of arginine and lysine, respectively, were depleted.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1092 ◽  
Author(s):  
Iris Scala ◽  
Maria Pia Riccio ◽  
Maria Marino ◽  
Carmela Bravaccio ◽  
Giancarlo Parenti ◽  
...  

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults. Few studies show that LNAAs may help in improving metabolic control as well as cognitive functions. In this study, 10 adult PKU patients with poor metabolic control were treated for 12 months with LNAAs (MovisCom, 0.8–1 g/kg/day) and underwent Phe and Tyrosine (Tyr) monitoring monthly. Neuropsychological assessment was performed at T0, T+3, and T+12 months by using the American Psychological General Well-Being Index, the Wisconsin Card Sorting Test, the Test of Attentional Performance, and the 9-Hole Peg Test. No change in plasma Phe levels was observed during LNAAs supplementation, while Tyr levels significantly improved during LNAAs supplementation (p = 0.03). Psychometric tests showed an improvement of distress and well-being rates, of executive functions, attention, and vigilance, whereas no difference was noted regarding hand dexterity. This study adds evidence of the advantage of LNAAs supplementation in improving cognitive functions and well-being in patients with PKU with poor metabolic control.


1998 ◽  
Vol 43 ◽  
pp. 53-53
Author(s):  
S Rastogi ◽  
K Abildskov ◽  
S S Daniel ◽  
M Garland ◽  
K Schulze ◽  
...  

Life Sciences ◽  
1983 ◽  
Vol 32 (14) ◽  
pp. 1651-1658 ◽  
Author(s):  
John D. Fernstrom ◽  
Madelyn H. Fernstrom ◽  
Marcia A. Gillis

2006 ◽  
Vol 29 (6) ◽  
pp. 732-738 ◽  
Author(s):  
R. Matalon ◽  
K. Michals-Matalon ◽  
G. Bhatia ◽  
E. Grechanina ◽  
P. Novikov ◽  
...  

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