Intravenous Infusion of α-Oxoisocaproate: Influence on Amino Acid and Nitrogen Metabolism in Patients with Liver Cirrhosis

1982 ◽  
Vol 62 (3) ◽  
pp. 285-293 ◽  
Author(s):  
L. S. Eriksson ◽  
L. Hagenfeldt ◽  
J. Wahren
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Intravenous Infusion ◽  
Aromatic Amino Acids ◽  
Control Subjects ◽  
Catheter Technique ◽  
Healthy Control ◽  
And Control ◽  
The Brain ◽  
Amino Acid Concentrations

1. The metabolic effect of α-oxoisocaproate (4-methyl-2-oxovalerate) infusion was examined in six patients with cirrhosis and in nine healthy control subjects. The arterial concentrations of amino acids, urea, ammonia, insulin and catecholamines were determined in the basal state and during intravenous infusion of α-oxoisocaproate (300 μmol/min) for 150 min. The exchanges of amino acids and substrates across the splanchnic region, the brain and the leg were examined in the healthy subjects by a catheter technique. 2. Basal α-oxoisocaproate levels were similar in patients and control subjects. During infusion the concentrations of α-oxoisocaproate rose to 90–130 μmol/l; they were 20–35% lower in the patients. Arterial leucine concentration increased in both groups to 250–300 μmol/l. Valine and isoleucine concentrations decreased (50–60%) as did to a lesser extent the concentrations of aromatic amino acids and methionine. 3. Regional exchange of amino acids was not significantly influenced by α-oxoisocaproate infusion. Arterial urea concentration decreased (12%, P < 0.05) and ammonia levels rose (15–25%, P < 0.05) in both groups. In the patients both adrenaline (100%, P < 0.001) and noradrenaline concentrations were elevated (350%, P < 0.001) in the basal state; insulin levels were similar to those in control subjects. 4. It is concluded that α-oxoisocaproate is rapidly transaminated to leucine in patients with cirrhosis and in healthy control subjects. α-Oxoisocaproate infusion resembles leucine infusion in its influence on aromatic amino acid concentrations, but in addition it elicits increased ammonia levels and decreased urea formation.

Influence of hyperinsulinaemia on intracellular amino acid levels and amino acid exchange across splanchnic and leg tissues in uraemia

1988 ◽  
Vol 74 (2) ◽  
pp. 155-163 ◽  
Author(s):  
Anders Alvestrand ◽  
Ralph A. Defronzo ◽  
Douglas Smith ◽  
John Wahren
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Concentrations ◽  
Amino Acid Exchange ◽  
Control Subjects ◽  
Intracellular Amino Acid ◽  
Resistance To Insulin ◽  
And Control ◽  
Amino Acid Concentrations ◽  
Acid Exchange

1. To examine whether insulin resistance in uraemia extends to amino acid metabolism, the effect of physiological hyperinsulinaemia on plasma amino acid concentrations was studied in 17 chronically uraemic and 28 healthy subjects by using the euglycaemic insulin clamp technique. 2. In six uraemic and seven control subjects, splanchnic and leg exchange of amino acids was quantified with hepatic and femoral venous catheterization, and in five uraemic and eight control subjects intracellular free amino acid concentrations were determined in muscle tissue obtained by needle biopsy. 3. In response to hyperinsulinaemia the plasma concentrations of all amino acids except alanine decreased by 10–50% in both uraemic and control subjects. Splanchnic alanine uptake declined by 20% and leg amino acid release tended to decrease in both groups. 4. The intracellular levels of all measured amino acids except alanine fell significantly and to a similar extent in uraemic and control subjects. 5. These results indicate that insulin-mediated alterations in regional amino acid exchange and in plasma and intracellular amino acid concentrations are similar in uraemic and control subjects. 6. It is concluded that tissue insensitivity to insulin in uraemia does not extend to uptake or release of amino acids and that resistance to insulin can be selective in its effect on different metabolic functions.

A Comparison of the Effects of Intravenous Infusion of Individual Branched-Chain Amino Acids on Blood Amino Acid Levels in Man

1981 ◽  
Vol 60 (1) ◽  
pp. 95-100 ◽  
Author(s):  
S. Eriksson ◽  
L. Hagenfeldt ◽  
J. Wahren
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Intravenous Infusion ◽  
Serum Insulin ◽  
Aromatic Amino Acids ◽  
Branched Chain Amino Acids ◽  
Blood Concentrations ◽  
Branched Chain Amino Acid ◽  
Amino Acid Levels ◽  
Branched Chain

1., Intravenous infusions of l-valine (600 μmol/min), l-isoleucine (150 μmol/min), l-leucine (300 μmol/min) and a mixture of the three branched-chain amino acids (70% l-leucine, 20% l-valine, 10% l-isoleucine; 270 μmol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P < 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.

Influence of Leucine on Arterial Concentrations and Regional Exchange of Amino Acids in Healthy Subjects

1980 ◽  
Vol 59 (3) ◽  
pp. 173-181 ◽  
Author(s):  
L. Hagenfeldt ◽  
S. Eriksson ◽  
J. Wahren
Keyword(s):  
Amino Acids ◽  
Renal Clearance ◽  
Healthy Subjects ◽  
Aromatic Amino Acids ◽  
Initial Value ◽  
Blood Concentrations ◽  
Arterial Blood ◽  
Catheter Technique ◽  
Methionine Uptake ◽  
The Brain

1. l-Leucine was given to healthy, post-absorptive subjects as a continuous intravenous infusion (300 μmol/min) during 2 1/2 h. Arterial blood concentrations and regional exchange of amino acids were measured across the splanchnic region, the brain and a leg, by the catheter technique. Renal clearance of amino acids was also determined. 2. During the infusion of leucine its concentration rose four- to six-fold, while the concentrations of several other amino acids declined continually, the effect being most pronounced for isoleucine (−55% of initial value), methionine (−55%), valine (−40%), tyrosine (−35%) and phenylalanine (−35%). 3. The infused leucine was taken up by muscle tissue (55%), by the splanchnic region (25%) and by the brain (10%). Neither leg-muscle release nor splanchnic uptake of aromatic amino acids was affected. Renal clearance and tubular reabsorption of amino acids were uninfluenced by leucine infusion. The uptake of isoleucine and methionine by the brain, seen in the basal state, was inhibited during leucine infusion. 4. The marked reduction in the concentrations of the aromatic amino acids, the uptake of leucine by the brain and the inhibition of brain methionine uptake, which accompany leucine infusion in healthy subjects,-5-be of relevance for the treatment of patients with portal-systemic encephalopathy.

scholarly journals Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

2007 ◽  
Vol 293 (1) ◽  
pp. E165-E171 ◽  
Author(s):  
Christopher D. Morrison ◽  
Xiaochun Xi ◽  
Christy L. White ◽  
Jianping Ye ◽  
Roy J. Martin
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Food Intake ◽  
Mtor Signaling ◽  
Acid Mixture ◽  
Mrna Levels ◽  
Amino Acid Availability ◽  
The Brain ◽  
Amino Acid Concentrations

Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake ( P < 0.05) and hypothalamic Agouti-related protein ( Agrp) gene expression ( P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 μg) suppressed 24-h food intake ( P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1–7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1–7 cells ( P < 0.01), and this effect was attenuated by replacement of the amino acid leucine ( P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1–7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids ( P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.

Changes in plasma amino acid concentrations in response to HIV-1 infection

1994 ◽  
Vol 40 (5) ◽  
pp. 785-789 ◽  
Author(s):  
G L Hortin ◽  
M Landt ◽  
W G Powderly
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Concentrations ◽  
Infected Group ◽  
Control Subjects ◽  
Immunodeficiency Virus ◽  
Amino Acid Profiles ◽  
Amino Acid Concentrations ◽  
Hiv 1

Abstract Plasma concentrations of 21 amino acids were determined for 20 control subjects and 20 subjects infected with human immunodeficiency virus type 1 (HIV). Compared with the control subjects, the HIV-infected group had lower cystine, tryptophan, and methionine (decreased 67%, 52%, and 32%, respectively, P &lt; 0.001 for each) and increased taurine (230%, P &lt; 0.001) and lysine concentrations (30%, P &lt; 0.001). Other amino acid concentrations changed modestly. Amounts of cystine, tryptophan, methionine, taurine, and lysine did not differ significantly between subgroups of HIV-infected subjects with &gt; 200 (n = 6) or &lt; 200 (n = 14) CD4+ lymphocytes per microliter, suggesting that the concentrations decrease soon after infection and change little thereafter. Activation of metabolism of cystine to taurine may explain reciprocal changes in these amino acids and known depletion of cystine and glutathione. The selective changes in amino acid profiles observed during HIV infection differ from those recognized for malnutrition or other pathological processes.

scholarly journals Regional Brain Analysis of Modified Amino Acids and Dipeptides during the Sleep/Wake Cycle

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 21
Author(s):  
Theodosia Vallianatou ◽  
Nicholas B. Bèchet ◽  
Mario S. P. Correia ◽  
Iben Lundgaard ◽  
Daniel Globisch
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Acid Metabolism ◽  
Aromatic Amino Acids ◽  
Brain Regions ◽  
Detection And Identification ◽  
The Central Nervous System ◽  
Neurophysiological Mechanisms ◽  
Amino Acid Analogues ◽  
The Brain

Sleep is a state in which important restorative and anabolic processes occur. Understanding changes of these metabolic processes during the circadian rhythm in the brain is crucial to elucidate neurophysiological mechanisms important for sleep function. Investigation of amino acid modifications and dipeptides has recently emerged as a valuable approach in the metabolic profiling of the central nervous system. Nonetheless, very little is known about the effects of sleep on the brain levels of amino acid analogues. In the present study, we examined brain regional sleep-induced alterations selective for modified amino acids and dipeptides using UPLC-MS/MS based metabolomics. Our approach enabled the detection and identification of numerous amino acid-containing metabolites in the cortex, the hippocampus, the midbrain, and the cerebellum. In particular, analogues of the aromatic amino acids phenylalanine, tyrosine and tryptophan were significantly altered during sleep in the investigated brain regions. Cortical levels of medium and long chain N-acyl glycines were higher during sleep. Regional specific changes were also detected, especially related to tyrosine analogues in the hippocampus and the cerebellum. Our findings demonstrate a strong correlation between circadian rhythms and amino acid metabolism specific for different brain regions that provide previously unknown insights in brain metabolism.

Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain

1976 ◽  
Vol 6 (2) ◽  
pp. 277-286 ◽  
Author(s):  
P. M. Daniel ◽  
S. R. Moorhouse ◽  
O. E. Pratt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Mental States ◽  
Monoamine Neurotransmitters ◽  
Motor Disability ◽  
Neuropsychiatric Diseases ◽  
Amino Acid Precursors ◽  
The Brain

SynopsisThere is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of control of movement and with certain neuropsychiatric diseases. These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood. In this study some factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain have been studied and the findings considered in relation to conditions in which the quantities of one or more of the monoamine neurotransmitters formed within the cerebral cells may be either too large or too small. Thus too little neurotransmitter will be formed if competition between amino acids for the carriers transporting them into the cerebral cells causes the exclusion of a large proportion of any of the aromatic amino acid precursors from the brain. For example, L-tryptophan is partially excluded from the brain if a raised level of any one of several other amino acids is maintained in the circulation. Of these, L-phenylalanine inhibits the transport of L-tryptophan into the brain most effectively, while aromatic amino acids in general exclude L-tryptophan more effectively than do other neutral amino acids.Over-production of one or more of the monoamine neurotransmitters is likely to occur when there is too much of one of the aromatic amino acid precursors in the brain cells as a result of abnormally high uptake from the blood, or as a result of their release by an excessive breakdown of the protein within these cells. Underproduction of neurotransmitters may occur in certain disease states, such as some aminoacidurias or Parkinsonism. We have listed some conditions associated with altered mental states or motor disability in which over- or under-production of monoamine neurotransmitters may occur and have tried to relate the findings in human disease with our experimental results.

Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity

1996 ◽  
Vol 270 (2) ◽  
pp. E273-E281 ◽  
Author(s):  
L. Luzi ◽  
P. Castellino ◽  
R. A. DeFronzo
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Amino Acid ◽  
Protein Metabolism ◽  
Plasma Amino Acid ◽  
Total Plasma ◽  
Control Subjects ◽  
Insulin Clamp ◽  
High Amino Acid ◽  
And Control

Seven normal glucose-tolerant obese subjects [ideal body weight (IBW) = 161%] and 18 controls (IBW = 102%) were studied with the euglycemic insulin clamp (10 and 40 mU.m-2.min-1) technique, [14C]leucine infusion, and indirect calorimetry to examine if the insulin resistance with respect to glucose metabolism extends to amino acid/protein metabolism. In the basal state, total plasma amino acid and leucine concentrations, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) were similar in obese and control subjects. During both low (10 mU.m-2.min-1)- and higher (40 mU.m-2.min-1)-dose insulin clamp studies, insulin-mediated glucose uptake was reduced in obese vs. control subjects (P < 0.01). During the last hour of the higher-dose insulin clamp step, the decrease in total plasma amino acids, branched-chain amino acids, and leucine concentration was impaired in obese vs. control subjects (P < 0.01). However, suppression of ELF and NOLD was similar in both groups. During the low-dose insulin clamp, the decrease in plasma leucine concentration, LO, and ELF all were impaired (P < 0.01). A second study was performed in which the total plasma amino acid concentration was increased two- to threefold in both groups. Under these conditions of low plasma insulin/high amino acid levels, LO and NOLD increased similarly in obese and control subjects. In conclusion, insulin resistance is a common feature of both glucose and protein metabolism in obesity. The defect in protein metabolism is characterized by an impairment of the ability of insulin to inhibit proteolysis; the stimulatory effect of hyperaminoacidemia on protein synthesis is intact in obesity.

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