Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat.

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.     

Plasma amino acids in rheumatoid arthritis

Plasma amino acid concentrations have been investigated in 12 female patients with rheumatoid arthritis (RA), who were hospitalized for two 14-day periods, one of which included 7 days of total fasting, whereas the other served as control period with normal food intake. All medical treatment was stopped on admission to the hospital. Plasma amino acid levels were repeatedly determined during both periods. Another group, consisting of 8 healthy volunteers, also underwent total fasting, for 6 days. The response to food deprivation with regard to plasma amino acid levels was compared with that in the RA patients. The results obtained from the control period were compared with those derived from age and sex matched healthy controls. RA disease was not characterized by a typical amino acid pattern. Major increases were seen in the concentrations of taurine, aspartate, glutamate, glycine, 1-methyl histidine, isoleucine and arginine. Rather smaller yet significant elevations could be observed in the levels of cystein, threonine, serine, citrulline, methionine and leucine. The only amino acid to show a lowered concentration was alpha-aminobutyrate. Most of the alterations induced by fasting were similar to those in healthy volunteers. An exception was the levels of taurine, which evidenced in RA patients a further increase during starvation, not observed in healthy volunteers, and valine which exhibited, a smaller increment than that apparent in healthy controls. The increase in sulphur-containing amino acids might be interpreted as a sign of an enhanced glutathione (GSH) catabolism, whereas the differing metabolic behaviour of branched chain amino acids (BCAA) suggests a specific reaction of valine in RA disease, similar to that in other catabolic diseases.     

Plasma concentration of amino acids in obese men consuming very-low-calorie diets composed of soy or collagen protein

The effects of soy or collagen protein, 1.3 g/kg desirable body weight per day, on fasting and postprandial plasma free amino acid concentrations were evaluated in eight obese men during a 40-day very-low-calorie reducing regimen. The interrelationships among individual plasma amino acids were also examined. In both protein-fed groups, fasting plasma histidine, phenylalanine, tyrosine, threonine and alanine levels decreased by day 40 whereas glycine increased. The decrease in plasma threonine and increase in plasma glycine were more pronounced in the collagen-fed group (n = 4) than in the soy-fed group (n = 4). Serine increased only in the collagen-fed group. The postprandial increases of all essential amino acids, with the exception of valine and phenylalanine, were less on day 26 than on day zero. Except for threonine levels, plasma amino acid profiles were similar during very-low-calorie dieting and during prolonged fasting. However, essential amino acid levels were better maintained by soy than by collagen protein diets.     

Partial substitution of amino acids of a parenteral solution with tripeptides: Effects on parameters of protein nutrition in baboons

We previously showed that triglycine and trileucine are efficiently utilized when infused intravenously (IV) in baboons who are fed a complete diet orally. In the present experiments we investigated the utilization of these tripeptides in the context of total parenteral nutrition. A group of subhuman primates (baboon) was subjected sequentially to two forms of total parenteral nutrition, each for a period of six days. The only difference between the two periods was that in one, all amino acids were given in free form, and in the other, the glycine and leucine components of the amino acid mixture were replaced with triglycine and trileucine, respectively. During both experimental periods the infusion solution provided daily 100 calories/kg body weight and 2.5 g amino acids/kg body weight. There were no significant differences between nitrogen balance, plasma amino acid concentrations, or urinary excretion of amino acids for the two forms of parenteral nutrition. The only exceptions were a greater plasma concentration of isoleucine and a greater urinary excretion of leucine during infusion of the partial peptide solution. Assimilation of triglycine and trileucine under the conditions of total parenteral nutrition was assessed by determining concentrations of these peptides in plasma and urine. Trileucine was not found in plasma, and only 1.8% of the amount of trileucine infused appeared as trileucine and dileucine in urine. Triglycine was detected in plasma and 17.1% of the amount of triglycine infused was excreted in urine as triglycine and diglycine. These data suggest that assimilation of trileucine and triglycine under the conditions of our experiment was sufficiently efficient to meet the daily need for an essential amino acid (leucine) and for nitrogen (glycine).     

Alanine-induced amino acid interrelationships.

Six normal subjects received 10 g of alanine both orally and as a 60-min intravenous infusion. In both studies blood samples for hormones and substrates were obtained every thirty minutes for 2 1/2 hour. Significant increases in whole blood levels of threonine, serine, glutamine, proline, glycine, and alpha-amino-n-butyric acid were found, which were mainly due to increases of these amino acids in the plasma compartment. In contrast, whole blood levels of leucine, valine, and isoleucine declined, mainly due to increases in the cell compartment. Plasma glucagon levels increased in both studies while insulin levels rose significantly only during the oral study. Plasma free fatty acids and blood glycerol levels declined while lactate and pyruvate increased. Glucose concentration did not change during both tests. These data suggest that the administration of large quantities of alanine is capable of inducing significant alterations in levels of other amino acids and substrates as well as changing hormone levels.     

A study of plasma free amino acid levels. II. Normal values for children and adults

Mean values for the fasting plasma levels of the individual amino acids are given for 136 children (aged 6–18 yr) and 194 adults. There are statistically significant differences between the mean values of boys and girls for only a few amino acids, but there are highly significant differences between the values for men and women for most of the amino acids. Men have higher levels than women for all the amino acids except glycine, serine, and threonine. Charts showing the mean values and variances of the amino acid levels of children and of men and women have been prepared. These allow a convenient medium on which to plot plasma amino acid analyses for easy detection of abnormal blood levels.     

荷肝癌小鼠血浆和肿瘤组织游离氨基酸代谢变化及其与肿瘤体积相关性研究

目的探讨荷肝癌小鼠游离氨基酸代谢变化,为肝癌患者氨基酸失衡疗法提供理论依据。方法采用HITACHIL8800型氨基酸分析仪,检测10例荷肝癌小鼠血浆和肿瘤组织游离氨基酸,并以10例正常小鼠做为对照组,研究氨基酸代谢变化与肿瘤体积的关系。结果荷瘤组血浆游离精氨酸、缬氨酸、丝氨酸、谷氨酸明显降低;肿瘤组织游离蛋氨酸、精氨酸、缬氨酸、亮氨酸与对应血浆游离氨基酸呈负相关;肿瘤组织游离异亮氨酸、缬氨酸、蛋氨酸、酪氨酸、亮氨酸、谷氨酸、丝氨酸与肿瘤体积呈正相关。结论肝癌在其生长过程中与某些特定氨基酸关系密切,这将为针对肝癌的氨基酸失衡处理提供实验和理论依据。     

Free serum amino acids for monitoring the therapy of female patients with breast cancer

A continuous monitoring by chromatographic determination of 10 free serum amino acids was carried out in 21 breast cancer patients. The results show, that the pretherapeutic levels of asparagine, glutamine, alanine, isoleucine, leucine, tyrosine and phenylalanine are significantly elevated if the disease progressed within the next two years. Asparagine, glutamine, glycine, alanine, tyrosine and phenylalanine are significantly elevated if no progression could be observed. In patients without progression the level of free serum amino acid went back to normal during one year. The determination of free serum amino acid is qualified for monitoring the treatment results in breast cancer patients.     

A study of plasma free amino acid levels. VIII. The relationship between plasma amino acid levels and I.Q. test performance

Fasting plasma free amino acid levels and standardized I.Q. scores for children participating in the Fels Longitudinal Study of growth and development were examined for possible relationships. Two partial replication samples were formed. One sample was composed of the first amino acid analysis made for a subject and the I.Q. score obtained nearest to it in time; the second sample consisted of the last analysis and the I.Q. test nearest to it. After age was linearly regressed from the amino acid levels, there were nontrivial correlations between amino acid level and I.Q. in both samples only in the case of tryptophan for boys and glycine for girls.     

The effect of amino acids and dipeptides on sodium and water absorption in man

A perfusion technique has been used to quantitate the effect of the amino acids glycine and alanine and the dipeptides glycyl-glycine and glycyl-L-alanine on sodium and water absorption from the human jejunum. Although no net absorption of sodium and water was seen in the absence of non-electrolytes, a significant stimulation occurred in the presence of both free amino acids and dipeptides. In the case of glycine and alanine, sodium and water absorption increased linearly with increasing concentration of the amino acid and saturation was not demonstrated over the range of concentrations studied. Molar ratios for net absorption of free amino acid and sodium were approximately 1:1 for all but the highest concentration of alanine. In contrast, the corresponding molar ratios for the two dipeptide solutions and sodium were approximately 1:2. Possible explanations for these observations are discussed.     

Insulin resistance in aged man: relationship between impaired glucose tolerance and decreased insulin activity on branched-chain amino acids

The effects of glucose-induced hyperinsulinemia on plasma amino acid levels were measured in 50 subjects divided into five age groups. Following an oral glucose load the plasma levels of most amino acids decreased, the decline being more pronounced for the three branched-chain amino acids (valine, isoleucine, and leucine). A progressive insulin resistance was proved on the basis of an age-related impaired glucose tolerance and a normal or increased insulin response. The plasma disappearance of branched-chain amino acids significantly correlated with age (r = -.514). The effects of the prevailing plasma insulin on branched-chain amino acids, measured by the ratio of amino acid changes per total insulin response, progressively declined in older subjects (P = .0005), and strictly correlated with age (r = .652). Insulin resistance in the elderly similarly affects glucose and branched-chain amino acid metabolism, with possible relevant effects on whole-body protein turnover.     

Serum amino acids in hepatic encephalopathy--effects of branched chain amino acid infusion on serum aminogram

Encephalopathic patients with cirrhosis of the liver consistently showed elevated levels of the aromatic amino acids, phenylalanine, tyrosine and free tryptophan as well as methionine in serum, whereas levels of the branched chain amino acids, valine, leucine and isoleucine, were depressed. Comatose patients with fulminant hepatitis had markedly elevated levels of all amino acids, the results being greatly different from those of cirrhotic patients. Molar ratios of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) decreased both in cirrhotics with and without encephalopathy and in cases with fulminant hepatitis. Infusion of a commercially available L-amino acid solution in a cirrhotic patient induced a strikingly abnormal aminogram documented in hepatic encephalopathy. Therefore, effects of branched chain amino acid infusion on the deranged amino acid pattern were primarily studied for the purpose of improvement in hepatic encephalopathy by normalization of serum amino acid patterns. Elevated levels of the aromatic amino acids and methionine could be apparently depressed in a cirrhotic patient by this type of infusion but not in a case of fulminant hepatitis probably because of the poor utilization of these amino acids in severely impaired liver.     

维持性血液透析患者血浆游离氨基酸检测的临床意义

目的　对维持血液透析患者的血浆游离氨基酸进行测定和分析。方法　用氨基酸自动分析仪测定 15例血透患者在一次透析前后的血浆氨基酸谱。结果　血透患者在透析前的必需氨基酸除苯丙氨酸外均较正常对照组降低 ,其中以缬氨酸、亮氨酸和组氨酸下降为显著 ;非必需氨基酸中精氨酸、甘氨酸和鸟氨酸明显升高 ;酪氨酸/苯丙氨酸和丝氨酸 /甘氨酸的比值较对照组明显降低。患者在一次透析后的必需和非必需氨基酸均低于透析前水平。结论　血透患者氨基酸异常的原因可能与蛋白质摄入不足、尿毒症毒性物质和酸中毒等有关     

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.     

Effects of pharmacologic hyperglucagonemia on plasma amino acid concentrations in normal and diabetic man

Four normal and five insulin dependent diabetic men received a 2 h pharmacologic glucagon infusion (50 ng/kg/min) resulting in plasma glucagon levels (4400 pg/ml) similar to those seen in glucagonoma patients. In normal subjects in whom plasma insulin concentrations rose significantly (239 uU/ml) and the blood level of 15 of the 18 amino acids measured fell significantly. In contrast, in the diabetic men who secreted no insulin in response to glucagon (no rise in C-peptide levels), only 10 of 18 amino acid levels fell significantly. The branched chain amino acids valine, leucine and isoleucine, as well as tyrosine and phenylalanine were among the 8 amino acids which showed no change in response to glucagon in the diabetics. Thus, glucagon appears to have no acute affect on branched chain amino acid levels in man.     

Plasma amino acids imbalance in patients with liver disease

The venous plasma amino acid patterns have been determined in 12 normal individuals and in 71 shunted and nonshunted cirrhotics in various grades of hepatic encephalopathy. The free amino acids have been determined by an amino autoanalyzer; the total and free tryptophan have been measured by a spoctrophotofluorimetric method. In 14 instances arterial plasma amino acid patterns have been measured simultaneously. High levels of aromatic and sulfurated amino acids and low levels of branched-chain amino acids have been constantly found in all cirrhotics. Methionine, phenylalanine, valine, leucine, tyrosine, and free tryptophan showed a statistical difference between controls and all other groups. These altered patterns did not correlate either with the grade or the evolution of the coma or with the presence of the surgical anastomosis. No statistical differences were lated with the grade and evolution of the hepatic encephalopathy was free tryptophan. The molar ratios between the amino acids sharing the same transport system across the blood-brain-barrier have been considered. A very good correlation with the grade of the mental disorder was found with the ratios free tryptophan/phenylalanine-tyrosine-methionine-valine-leucine-isoleucine and free tryptophan/branched-chain amino acids.This work was supported by Grant 30.3.1971, no. 118, 500.6/Contract 72, from Ministero della Sanita. Dir. Gen. Sery. Med. Soc., Div. VI.     

Rapid changes in urinary serine and branched-chain amino acid excretion among diabetic patients during insulin treatment

In a preliminary experiment, we found a good correlation between 24-h urinary amino acid excretion and the 24-h average plasma levels of the same amino acids. Examining diabetics who were just beginning insulin therapy, we found that insulin normalized the abnormally high levels of excretion of branched-chain amino acids and serine. Interestingly, when expressed in terms of mol/g of creatinine, the normalization of serine excretion brought about by insulin was roughly equal to the normalization of glycine excretion brought about by insulin (-0.39 mM/g of creatinine vs. + 0.33 mM/g of creatinine over 24 h). Since plasma serine is primarily produced in the kidneys from glycine, this suggests that insulin affects the regulation of the serine-glycine metabolic pathway. In turn, measurement of urinary serine and glycine may provide a useful gauge of insulin activity in the tissues, including the kidneys.     

Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.     

Reduction of large neutral amino acid concentrations in plasma and CSF of patients with maple syrup urine disease during crises

Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of this disorder are poorly understood. We determined the concentrations of all amino acids in plasma of patients with MSUD during crises (with severe CNS symptoms) and after recovery in the hope of detecting possible alterations of these levels during metabolic decompensation. Blood samples obtained from 11 children with MSUD aged 1 month to 7 years and from 10 age-matched controls (5 months to 6 years) with no evidence of metabolic disease were examined for their amino acid content by high-performance liquid chromatography. We observed that leucine, isoleucine and valine concentrations were respectively 30, 9 and 3 times higher than normal values, whereas the concentrations of the large neutral amino acids (LNAA) phenylalanine, tyrosine, tryptophan and methionine were significantly lower during metabolic decompensation as compared to the controls. In addition, concentrations of leucine, but not of valine or isoleucine, were inversely related to the LNAA concentrations in plasma. The concentrations of these amino acids in plasma returned to normal values when patients were clinically well. CSF amino acid concentrations also showed decreased amounts of LNAA and increased concentrations of branched-chain amino acids. It is possible that the decrease in plasma concentrations of LNAA may lead to a deficit of these essential amino acids in the brain as well as of their products such as proteins and neurotransmitters, a fact that might be related to the neurological dysfunction of MSUD.     

A study of plasma free amino acid levels. IV. Characteristic individual levels of the amino acids

Fasting plasma amino acid analyses made on blood from the same subjects on four occasions at yearly intervals were available for 35 boys and 26 girls. These subjects tended to maintain the same relative plasma level of most of the amino acids over the $\text{3–3}\text{1}\text{2}\text{-}\text{yr}$ period during which blood samples were taken. This demonstrated the existence of characteristic individual patterns of plasma amino acid levels. Correlations between individual amino acid levels and some physical growth characteristics were examined. These included body build and age of peak height velocity for boys and girls and age of menarche for girls. There were only a few statistically significant correlations, which showed little consistency.