Leg Metabolism of Amino Acids and Ammonia in Patients with Chronic Renal Failure

1985 ◽  
Vol 69 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Giacomo Deferrari ◽  
Giacomo Garibotto ◽  
Cristina Robaudo ◽  
Alberto Canepa ◽  
Serena Bagnasco ◽  
...  

1. Leg metabolism of amino acids and ammonia in the postabsorptive state was evaluated in 10 patients with chronic renal failure (CRF) and in 10 patients with normal renal function (controls) by measuring the arterial-femoral venous (A-FV) differences for free amino acids and ammonia. 2. Total amino acid release from the leg and alanine and glutamine release, which accounts for the greatest amount of the total amino acid release, are similar in patients and controls. Total amino acid uptake from the arterial blood and glutamate uptake, which is the amino acid extracted at the highest rate, are comparable in both groups. Taken together these data, in addition to the similarity of A-FV differences for proteolytic markers, namely tyrosine, phenylalanine and histidine, suggest that protein breakdown in peripheral tissues is not increased in patients with CRF. 3. In CRF selective metabolic abnormalities for some amino acids are evident. Whilst only the A-FV differences for valine, leucine and isoleucine are decreased, additional alterations are observed by relating the A-FV difference for each amino acid to that of proteolytic markers. Such a procedure demonstrates that in CRF histidine release relative to that of proteolytic markers is reduced, whereas proline and arginine release is increased. 4. In CRF the reduced release of some amino acids, mainly branched-chain amino acids, by the leg probably affects the pattern of circulating amino acids. 5. Finally, both in patients and in controls a significant uptake of ammonia is observed; the ammonia uptake is related to arterial levels of this metabolite, confirming the role of peripheral tissues in removing ammonia from circulation.

1980 ◽  
Vol 238 (1) ◽  
pp. E32-E37
Author(s):  
C. Karakash ◽  
F. Rohner-Jeanrenaud ◽  
B. E. Hustvedt ◽  
B. Jeanrenaud

Several aspects of nitrogen metabolism have been studied in adult nonhyperphagic, hyperinsulinemic, ventromedial hypothalamus (VMH)-lesioned rats. Ten days postoperatively, VMH-lesioned rats had high plasma levels of urea and low plasma tyrosine, while plasma alanine, glutamine, total amino acid, and protein levels were unaltered. Urea production and excretion were increased in VMH-lesioned rats. Increased urea synthesis could not be attributed to enhanced peripheral release of amino acids. In vitro, measurements of hepatic amino acid uptake and liver protein synthesis did not reveal any disturbances of these processes in VMH-lesioned rats. However, hepatic transamination and lipogenesis from amino acids were increased following VMH-lesions. In addition to the hyperinsulinemia previously reported to occur in nonhyperphagic VMH-lesioned rats, this study showed an increased glucagon secretion from perfused pancreases of these animals. These data together suggest that the excess of the two hormones at the portal vein of VMH-lesioned rats would favor uptake and deamination of amino acids, their diversion to lipid synthesis and possibly other pathways, with consequent increase in urea production and reduced supply of amino acids to peripheral tissues available for nitrogen retention.


1995 ◽  
Vol 268 (3) ◽  
pp. R759-R770
Author(s):  
D. A. MacLean ◽  
J. K. Barclay ◽  
T. E. Graham

This study examined the effects of electrical stimulation on amino acid and ammonia (NH3) metabolism in the isolated in situ canine gastrocnemius muscle preparation. Cut sciatic nerves of 10 mongrel dogs were stimulated at either 3 or 5 twitches/s (10 V, 0.2-ms duration) for 60 min. Muscle NH3 release dramatically increased on stimulation, and over 60 min the 3- and 5-Hz groups released 86.7 +/- 24.2 vs. 160.8 +/- 17.4 mumol.min-1.100 g-1 (P < 0.05) of NH3, respectively. Similarly, the intramuscular NH3 concentration was elevated (P < 0.05) above rest for both groups throughout stimulation, and it was higher (P < 0.05) at 5 min for the 5-Hz (82.7 +/- 2.4 mumol/100 g wet wt) than for the 3-Hz (67.4 +/- 7.4 mumol/100 g wet wt) group. Stimulation was also characterized by a large release of amino acids by both groups. The total amino acid release for 60 min was 415.4 +/- 64.9 vs. 193.3 +/- 56.2 (P < 0.05) mumol/100 g for the 3- and 5-Hz groups, respectively. However, there were no shifts or differences between groups in the intramuscular total amino acid pools. Glutamine (Gln) and alanine (Ala) dominated the amino acids released by muscle and together represented 35 and 46% of the total amino acids released over 60 min for the 3- and 5-Hz groups, respectively. The total release of Gln was higher (P < 0.05) for the 3-Hz (81.1 +/- 5.6 mumol/100 g) than for the 5-Hz (49.4 +/- 10.7 mumol/100 g) group, but there were no differences between groups in total Ala release. In contrast, both groups demonstrated an uptake of branched-chain amino acids (valine, isoleucine, and leucine) after 45 min of stimulation. These data show a stimulation-dependent production of NH3 and release of amino acid by the canine gastrocnemius muscle. These data further show that the degree of net muscle NH3 production is proportional to the frequency, whereas the degree of amino acid release is an inverse function of frequency.


1981 ◽  
Vol 38 (2) ◽  
pp. 157-162 ◽  
Author(s):  
Wayne S. Gardner ◽  
Warren H. Miller III

Excretion of free amino acids and ammonia by Daphnia magna was measured by examining in vitro changes in concentration of the two forms of nitrogen over 4–6 h. Mean weight-specific amino acid release rate (± SE) for 32 healthy daphnids was 0.13 ± 0.03 nmol (mg dry wt)−1∙h−1 as compared with a mean ammonia excretion rate of 21 ± 2 nmol (mg dry wt)−1∙h−1. Net removal from solution was observed when low levels of amino acids (2 nmol/8 mL) were added to the water before incubation, indicating that measured net release rates could be reduced by amino acid uptake. Toxic levels (0.5 mg∙L−1) of lead, arsenic, Kepone, toxaphene, malathion, or pentachlorophenol, added to stress the animals, did not significantly affect release rates of amino acids or ammonia, but the addition of copper (as CuSO4) increased amino acid release by daphnids and hindered microbial removal of amino acids from incubation waters. Amino acids released from copper-exposed animals were similar in composition to those in intracellular amino acid pools of D. magna, suggesting that diffusion across cell membranes may have been the mechanism for amino acid release.Key words: amino acids, ammonia, cladocera, contaminants, copper, Daphnia, excretion, free amino acids, stress, zooplankton


1982 ◽  
Vol 52 (5) ◽  
pp. 1250-1256 ◽  
Author(s):  
O. L. Smith ◽  
G. Huszar ◽  
S. B. Davidson ◽  
E. Davis

To test the effects of acute cold on muscle amino acid and protein 1) rats were exposed to 4 degrees C for 24 h, functionally hepatectomized (eviscerated) and accumulation in the blood used to indicate changes in amino acid release from the tissues; 2) other rats were left intact, and urinary excretion of 3-methylhistidine (proportional to muscle protein breakdown) determined during cold exposure. In the eviscerated group, cold enhanced loss of total amino acids from the tissues (as alpha-amino nitrogen), but the loss (213 +/- 14.8% of basal in 2 h) was not due to excess alanine (180 +/- 8.5%). By comparison, in fasted rats total amino acid was 182 +/- 12.3, alanine 309 +/- 17.2%. Also, the cold-induced loss resembled the effects of streptozotocin diabetes and depended on a depression by cold of serum insulin (to 35.7 +/- 2.3 muU/ml). Therefore it was prevented when insulin was restored by infusion (40 mU . 100 g-1 . h-1) or by adrenodemedullation before cold exposure. Epinephrine (10 micrograms/100 g sc) depressed insulin in the latter and permitted amino acid release to recur. In intact rats, 3-methylhistidine excretion was unaffected by cold. The results suggest that although cold fails to stimulate alanine synthesis or protein breakdown, it inhibits insulin release sympathetically, thereby diminishing the amount of amino acid incorporated into muscle protein.


2003 ◽  
Vol 98 (3) ◽  
pp. 729-733 ◽  
Author(s):  
Yi Feng ◽  
Minglei Cui ◽  
William D. Willis

Background Gabapentin has recently been used clinically as an antihyperalgesic agent to treat certain neuropathic pain states. The aim of this study is to test whether gabapentin is able to inhibit responses to peritoneal irritation-induced visceral pain and to examine the effect of gabapentin on spinal cord amino acid release. Methods The acetic acid-induced writhing assay was used in rats to determine the degree of antinociception. The rats received an intraperitoneal injection of acetic acid 40 min after intraperitoneal administration of vehicle or gabapentin (50, 100, or 200 mg/kg). Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space in anesthetized rats. Acetic acid-induced release of amino acids into the dialysate, including glutamate, aspartate, serine, glutamine, and glycine, following intraperitoneal injection of acetic acid was evaluated by measurements of changes in the concentrations of these amino acids. The effects of pretreatment with saline or gabapentin (100 mg/kg intraperitoneal) on amino acid release were compared. Results Gabapentin reduced writhing responses in a dose-related fashion. Dialysate concentrations of glutamate, aspartate, and serine increased significantly following intraperitoneal injection of acetic acid, while glutamine and glycine concentrations were not increased significantly. When compared to saline-treated rats, animals pretreated with 100 mg/kg gabapentin showed suppression of the acetic acid-induced increases in glutamate, aspartate, and serine concentrations. Conclusions These data demonstrate that gabapentin effectively inhibits acetic acid-induced nociception, and the antinociceptive effect of gabapentin correlates with the suppression of noxious-evoked release of excitatory amino acids in the spinal cord.


1977 ◽  
Vol 166 (1) ◽  
pp. 49-55 ◽  
Author(s):  
A Palou ◽  
L Arola ◽  
M Alemany

Plasma amino acid concentrations were determined in virgin female rats, in pregnant rats (12 and 21 days after impregnation) and in 21-day foetuses. The total amino acid concentration in plasma decreases significantly with pregnancy, being lower at 12 than at 21 days. Alanine, glutamine+glutamate and other ‘gluconeogenic’ amino acids decrease dramatically by mid-term, but regain their original concentrations at the end of the pregnancy. With most other amino acids, mainly the essential ones, the trend is towards lower concentrations which are maintained throughout pregnancy. These data agree with known nitrogen-conservation schemes in pregnancy and with the important demands on amino acids provoked by foetal growth. In the 21-day foetuses, concentrations of individual amino acids are considerably higher than in their mothers, with high plasma foetal/maternal concentration ratios, especially for lysine, phenylalanine and hydroxy-proline, suggesting active protein biosynthesis and turnover. All other amino acids also have high concentration ratios, presumably owing to their requirement by the foetuses for growth. Alanine, glutamine+glutamate, asparagine+aspartate, glycine, serine and threonine form a lower proportion of the total amino acids in foetuses than in the virgin controls or pregnant rats, probably owing to their role primarily in energy metabolism in the adults. The results indicate that at this phase of foetal growth, the placental amino acid uptake is considerable and seems to be higher than immediately before birth.


1999 ◽  
Vol 50 (3) ◽  
pp. 413 ◽  
Author(s):  
J. Lee ◽  
R. J. Knutson ◽  
S. R. Davis ◽  
K. Louie ◽  
D. D. S. Mackenzie ◽  
...  

Five multiparous Saanen goats in late lactation were infused with 35S-cysteine into the mammary gland via the external pudic artery. A further 2 goats were infused with 35S-methionine via the same artery and later with 35S-methionine into the jugular vein. Total uptake of cysteine from the arterial blood supply by the mammary gland was approximately 6% of the 35S-cysteine flux past the gland, whereas uptake of methionine was 30–40%. Total mammary uptake of cysteine was also lower than that of methionine when expressed as a percentage of whole body utilisation (6.5 and 14%, respectively). The uptake from the blood did not account for output in the milk for either cysteine or methionine. Both amino acids were highly conserved by the gland as shown by little release of any degraded constitutive protein amino acids and no evidence of oxidation products of either cysteine or methionine being released into the blood. Comparison of 35S activity in the milk from the infused and non-infused sides of the gland showed up to 10% trans-sulfuration of methionine to cysteine within the gland, none of which was exported in the venous drainage. Total ATP production by one side of the gland was 12.1 mol/day or 13 mmol/min.kg mammary tissue, of which 15% was required for gland protein synthesis. The experimental measurements from both the cysteine and methionine infusions were used to solve a model of gland amino acid uptake and partitioning. Modelling radioactivity of both amino acids in the blood, intracellular free pool, and milk protein suggested that a single intracellular pool cannot be the only source of amino acid for protein synthesis. The model also provides support for the hypothesis that a significant proportion of the uptake of at least some amino acids by the mammary gland is from intracellular hydrolysis of extracellularly derived peptides.


1982 ◽  
Vol 242 (5) ◽  
pp. R570-R576
Author(s):  
J. A. O'Connor ◽  
R. L. Scott ◽  
P. W. Mellick ◽  
M. D. Caldwell

We established an isolated perfused rat hindlimb wound model using intramuscular injections of lambda-carrageenan. Wound and control hindlimbs of 24-h fasting anesthetized (phenobarbital sodium, 5 mg/100 g body wt) rats were perfused for 60 min (10 ml/min) with media containing 10 mM glucose and physiological levels of amino acids. Analysis of perfusate showed a significant increase in glucose clearance and lactate production from the wounded hindlimb but no significant difference in tissue adenine nucleotide levels. Alterations in net amino acid release were measured over a 60-min period; all amino acids were released in greater concentration from wounded hindlimbs. Comparison of amino acid release, normalized for phenylalanine concentration, suggested the following alterations in amino acid metabolism by the wounded tissue: depressed threonine, glycine serine and alanine release, and increased release of the branched chain amino acids (BCAA), leucine, isoleucine, and valine. The increased release and intracellular concentration of BCAA was supported by decreased BCAA transaminase activity in the wounded muscle tissue. This result may explain the decreased alanine release from the wounded hindlimbs.


2006 ◽  
Vol 100 (6) ◽  
pp. 1822-1830 ◽  
Author(s):  
Marina Mourtzakis ◽  
Bengt Saltin ◽  
Terry Graham ◽  
Henriette Pilegaard

During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline in pyruvate production could affect tricarboxycylic acid cycle flux as well as gluconeogenesis. To enhance our understanding of these interactions, we studied the time course of changes in substrate utilization in six men who cycled at 44 ± 1% peak oxygen consumption (mean ± SE) until exhaustion (exhaustion at 3 h 23 min ± 11 min). Femoral arterial and venous blood, blood flow measurements, and muscle samples were obtained hourly during exercise and recovery (3 h). Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased for the remainder of the exercise bout ( P < 0.05). PDH activity peaked at 2 h of exercise, whereas pyruvate production peaked at 1 h of exercise and was reduced (∼30%) thereafter, suggesting that pyruvate availability primarily accounted for reduced carbohydrate oxidation. Increased free fatty acid uptake ( P < 0.05) was also associated with decreasing PDH activity ( P < 0.05) and increased PDH kinase 4 mRNA ( P < 0.05) during exercise and recovery. At 1 h of exercise, pyruvate production was greatest and was closely linked to glutamate, which was the predominant amino acid taken up during exercise and recovery. Alanine and glutamine were also associated with pyruvate metabolism, and they comprised ∼68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism in early exercise.


Sign in / Sign up

Export Citation Format

Share Document