Arterial Concentrations Of Alanine Research Articles

Effects of adrenalectomy on urea synthesis in rats.

The effect of depletion of glucocorticoids on the dynamics of hepatic amino-N conversion was examined 2 and 7 days after adrenalectomy in a total of 22 rats substituted by adrenaline. The capacity of urea synthesis was studied by infusion of alanine under steady state conditions with arterial concentrations of alanine between 7.3 and 11.6 mmol/l. The animals were nephrectomized and the capacity was calculated as accumulation of urea in total body water corrected for intestinal hydrolysis. Adrenalectomy reduced the capacity of urea synthesis to 55% of the capacity for control rats and reduced the alanine metabolic rate to 60%. In control rats the urea synthesis exceeded the alanine infusion by indicating an extrahepatic tissue release of amino acids. This difference disappeared after adrenalectomy. The body weight and food intake did not change during the study period. Thus lack of glucocorticoids influences the in vivo nitrogen economy both by decreasing the liver function as to conversion of amino-nitrogen and by decreasing release of tissue amino-nitrogen.

Alanylglutamine reduces muscle loss of alanine and glutamine in post-operative anaesthetized dogs.

1. The present study examined the effect of an infusion of the dipeptide alanylglutamine or of the corresponding amino acids alanine and glutamine in equimolar amounts (10 mumol min-1 kg-1) on the canine hindlimb exchange of alanine and glutamine in the post-operative anaesthetized dog. In contrast to glutamine, the dipeptide alanylglutamine is stable in aqueous solution and therefore would be a suitable substrate for parenteral nutrition. 2. The infusion of alanylglutamine increased (a) the arterial concentration of alanylglutamine to a plateau level (120 +/- 9.5 mumol/l, mean +/- SEM) 20 min after start of the infusion, (b) the mean arterial alanine concentration from 761 +/- 42 to a plateau of 1500-1700 mumol/l (P greater than 0.01) and (c) the arterial glutamine concentration from 407 +/- 51 to a plateau of 1050-1500 mumol/l (P greater than 0.01). Alanine and glutamine levels were slightly higher (14% and 26%, respectively, NS) in the group receiving the equimolar amount of alanine and glutamine. 3. Infusion of alanylglutamine for 1 h abolished the net efflux of glutamine (from -0.80 +/- 0.1 to -0.03 +/- 0.2 mumol min-1 kg-1; P greater than 0.05) and invoked a net influx of alanine (from -0.50 +/- 0.19 to +0.27 +/- 0.14 mumol min-1 kg-1; P greater than 0.01). These changes were similar to those achieved when the two amino acids were infused. 4. This study demonstrates that during short-term administration of alanylglutamine or of the corresponding amino acids the nitrogen release from the hindlimb of the anaesthetized post-operative dog via alanine and glutamine is reduced.

Effect of alanine concentration independent of changes in insulin and glucagon on alanine and glucose homeostasis in the conscious dog

The effect of an alanine load per se on hepatic alanine balance and hepatic glucose production is unclear. To examine this question, alanine was infused into six postabsorptive dogs at a rate of 6 μmol/kg-min, while maintaining insulin and glucagon levels using the pancreatic clamp technique. The arterial alanine concentration rose from a basal level of 227 ± 16 μmol/L to 497 ± 40 μmol/L during alanine infusion ( P < .01). The net hepatic fractional extraction of alanine remained unchanged, while hepatic alanine uptake increased from 3.0 ± 0.3 to 6.0 ± 0.4 μmol/kg-min ( P < .01). Conversion of alanine into glucose increased 87% to 2.7 ± 0.3 μmol/kg-min during alanine infusion ( P < .01) while gluconeogenic efficiency remained essentially unchanged. Despite the increased gluconeogenic rate, the total rate of glucose production was unchanged. These data suggest that an increase in the alanine load to the liver causes a proportional increase in net hepatic alanine uptake and the gluconeogenic rate, but that in an overnight fasted animal this increase is insufficient to significantly increase glucose production.

Alterations in Myocardial Uptake of Glutamate and Release of Alanine After Propranolol, Nifedipine, and Glyceryl Trinitrate in Coronary Artery Disease

We examined the effects of antianginal drugs on myocardial uptake of glutamate and release of alanine in patients with chronic effort angina. Thirty-three patients underwent two periods of atrial pacing, the second preceded either by no medication (controls) (n = 8), 0.1 mg/kg i.v. propranolol (n = 8), 30 mg nifedipine sublingually (n = 9) or 0.75 mg glyceryl trinitrate sublingually (n = 8). Before, during, and after each pacing period, coronary sinus blood flow (CSBF), oxygen uptake, and arteriocoronary sinus differences (ACs) of plasma glutamate and alanine were determined. In all groups of patients, arterial alanine concentration fell during the second test. Except for this fall, no metabolic change was seen in controls. Propranolol increased circulating arterial concentration and ACs values of glutamate throughout the test. Nifedipine did not change arterial glutamate concentration but decreased ACs glutamate before and after pacing. Glyceryl trinitrate decreased CSBF, oxygen uptake, and net myocardial uptake of glutamate before pacing despite unchanged arterial level and ACs values. Alterations of myocardial glutamate uptake after drugs may reflect metabolic effects of propranolol primarily exerted on extracardial sites and of nifedipine exerted on the myocardium itself, whereas changes after glyceryl trinitrate seem to be secondary to its cardiac unloading effect. Alterations in myocardial release of alanine were too small and inconsistent to be taken as drug effects.

Alanine production by the human fetus at term gestation.

In a previous study, we demonstrated the complete dependence of the human fetus on the mother for its glucose needs. As alanine is considered the major glucogenic amino acid synthesized endogenously and an important source of urea nitrogen, in the present study we examined whether the human fetus at term gestation can produce alanine. 5 normal pregnant women, undergoing elective cesarean section, were given a constant infusion of [2,3-13C2]alanine in trace quantities for a period of 4 h prior to and during surgery. Isotopic steady state was achieved in the maternal blood by 1.5 h and maintained through anesthesia and surgery. The 13C enrichment (mol% excess) of alanine was measured in the peripheral blood of the mother and in the simultaneously obtained umbilical arterial and venous blood at delivery. Even though the umbilical venous and arterial concentrations of alanine were similar, a 42% decrease in 13C enrichment of alanine occurred between umbilical vein and artery, 1.00 +/- 0.23 and 0.58 +/- 0.15%, respectively (mean +/- SD). These data suggest that the human fetus at term gestation following an overnight maternal fast produces alanine endogenously. This may serve to transfer nitrogen from fetal muscle to the liver for urea synthesis.

The effects of acute acidosis on alanine and glucose metabolism across the liver, gut, kidney, and muscle in the dog

Acute metabolic acidosis (AMA) in the dog results in a 48% increase in arterial alanine concentration and an 11% fall in blood glucose. Extraction/production of glucose and alanine were studied by A/V sampling and electromagnetic blood flow probe measurements. Alanine and total amino-N release by muscle increased in acidosis Hepatic glucose release was reduced. More marked changes in metabolism occur in AMA in the dog than previously considered.

Amino acid release from the hindquarter and urea appearance in acute uremia.

Hepatic urea production is increased in acutely uremic rats, but it is not known whether this is related to release of nitrogen from nonhepatic tissues. Rats with acute uremia had lower arterial concentrations of alanine, glutamine, and alpha-amino nitrogen when compared to sham-operated rats and released significantly more alpha-amino nitrogen from the hindquarter in situ. Release of alpha-amino nitrogen, alanine, and glutamine from the perfused hindquarter of acutely uremic rats was greater than that of sham-operated rats. These changes in situ and in the perfused hindquarter were more pronounced in rats deprived of food and water compared to fed animals and were not due to depletion of intracellular amino acids. In addition to increased amino acid nitrogen release, there was a higher urea appearance rate (excretion plus accumulation) in starved, uremic rats compared to sham-operated controls (244.7 +/- 11.2 vs. 182.0 +/- 12.4 mg. 100 g-1 .48 h-1); urea appearance also was suppressed partially by feeding. Both peripheral release of amino acids and diet influence waste nitrogen production in acute uremia.

Transport of amino acids in whole blood and plasma of sheep.

Comparisons of amino acid transport in both whole blood and plasma were made across the portal-drained viscera, liver, kidneys, and hindquarters in sheep. Lyophilized samples could be stored at -20 degrees C for up to 17 wk with little or no changes observed on reanalysis. Only glutamine, taurine, and serine showed any loss (18, 23, and 16%) over a 3.5-yr period. However, there was no concomitant rise in glutamate over the same period, suggesting that glutamate does not simply deamidate. There were no differences in arterial concentrations of alanine, citrulline, isoleucine, and valine between whole blood and plasma. However, glutamate, asparagine, glycine, serine, threonine, taurine, ornithine, leucine, lysine, phenylalanine, and tyrosine were higher in whole blood compared to plasma, and glutamine and arginine were lower. Whole blood and plasma fluxes for all amino acids were positively correlated, and there were no differences in their regression lines among tissues. Plasma, however, underestimated amino acid transport glutamine, glutamate, and taurine at greater rates than plasma. It is concluded that blood cellular transport, per unit volume, was always concomitant to and usually at the same rate as plasma transport over all tissues measured. Plasma therefore reflects amino acid transport but underestimates total transport to about the extent of the packed cell volume and in cases of glutamine, glutamate, and taurine, perhaps even more.

Amino Acid Metabolism in Patients with a Hereditary Myopathy and Paroxysmal Myoglobinuria

ABSTRACT Amino acid metabolism of skeletal muscle was examined in two patients with a hereditary myopathy associated with elevated blood levels of lactate and pyruvate and paroxysmal myoglobinuria. Arterial concentrations as well as arm and leg exchange, respectively, of amino acids, lactate, pyruvate and oxygen were studied at rest and during exercise (16 and 33 W) using a bicycle ergometer. The patients' arterial concentrations of amino acids, lactate and pyruvate in the resting state were similar to those of healthy controls. During exercise a marked increase in lactate and pyruvate concentrations was seen in the patients, exceeding the small rise in healthy controls. The arterial alanine concentration rose during exercise in both patients (+120%, +125%), while no change was observed in the controls working at the same work load. No other amino acid showed a consistent rise during exercise. Instead, the arterial levels of the branched chain amino acids (valine, leucine, isoleucine) fell during exercise in the patients but not in the controls. Net release of alanine from the legs in patient 1 rose 2.5‐ and five‐fold during exercise, while no change was seen in the controls. Alanine output from the working arms in patient 2 exceeded that of controls by 50%. In addition, the release of lactate and pyruvate during exercise was much augmented in both patients in comparison to controls. It is concluded that the rate of alanine formation by skeletal muscle during exercise is much increased in patients with this type of myopathy, associated with elevated levels of lactate and pyruvate. These findings lend support to the theory that the carbon skeletons for alanine synthesis by skeletal muscle are derived from muscle glycolysis.

Ethanol effects of substrate utilization by the human brain

Arterial concentrations and arterio-jugular vein differences of ethanol, acetate, glucose, lactate, pyruvate, glycerol, free fatty acids and ketone bodies were determined in seven healthy male volunteers before and during an infusion of ethanol, which gave a blood alcohol concentration of about 12 mmol/l. Arterial-jugular vein (A-JV) oxygen differences were unchanged throughout the study. Ethanol caused a small reduction in blood glucose concentration, from a mean of 5.1 to 4.7 mmol/l, and the A-JV difference fell significantly. When alcohol was given, arterial acetate concentration rose quickly to about 1 mmol/l and was unchanged thereafter. All subjects had a positive arterio-venous difference for acetate. Arterial lactate concentration was doubled by ethanol and the normal release from the brain was abolished. Arterial alanine concentration decreased significantly, from 0.19 to 0.16 mmol, when alcohol was given but no net exchange by the brain could be observed. It is concluded that: (a) acetate can be taken up by the brain and if totally oxidized, could account for 6% of the oxygen consumption; (b) glucose arterial-jugular vein difference is decreased by ethanol, suggesting an attenuation in glucose uptake; and (c) lactate net release is abolished by alcohol, probably due to the increased arterial concentration.

Ethanol effects of substrate utilization by the human brain

Arterial concentrations and arterio-jugular vein differences of ethanol, acetate, glucose, lactate, pyruvate, glycerol, free fatty acids and ketone bodies were determined in seven healthy male volunteers before and during an infusion of ethanol, which gave a blood alcohol concentration of about 12 mmol/l. Arterial-jugular vein (A-JV) oxygen differences were unchanged throughout the study. Ethanol caused a small reduction in blood glucose concentration, from a mean of 5.1 to 4.7 mmol/l, and the A-JV difference fell significantly. When alcohol was given, arterial acetate concentration rose quickly to about 1 mmol/l and was unchanged thereafter. All subjects had a positive arterio-venous difference for acetate. Arterial lactate concentration was doubled by ethanol and the normal release from the brain was abolished. Arterial alanine concentration decreased significantly, from 0.19 to 0.16 mmol, when alcohol was given but no net exchange by the brain could be observed. It is concluded that: (a) acetate can be taken up by the brain and if totally oxidized, could account for 6% of the oxygen consumption; (b) glucose arterial-jugular vein difference is decreased by ethanol, suggesting an attenuation in glucose uptake; and (c) lactate net release is abolished by alcohol, probably due to the increased arterial concentration.

Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man.

To evaluate the role of splanchnic and peripheral tissues in the disposal of an oral glucose load, splanchnic exchange of glucose, lactate, pyruvate, glycerol and amino acids was determined in ten healthy subjects in the basal state and for three hours following the oral ingestion of 100 gm. of glucose. Following glucose ingestion, splanchnic glucose output rose rapidly, reaching values two to three times the basal rate at fifteen minutes and returning to baseline by ninety minutes. A secondary rise in splanchnic glucose output occurred at 150 minutes and coincided with a secondary increment in arterial glucose. Total splanchnic glucose output over three hours was 40 plus or minus 3 gm., representing a total increase of only 15 plus or minus 3 gm. above basal splanchnic glucose output. The peak rise in blood glucose was directly proportional to the increase in splanchnic glucose output. Arterial concentrations of alanine, lactate and pyruvate rose by 15, 65 and 80 per cent, respectively, following oral glucose. These arterial elevations were preceded by a 75-100 per cent inhibition of splanchnic uptake of alanine and lactate; in the case of pyruvate there was a reversal from a net uptake in the basal state to a significant net splanchnic output after glucose ingestion. Arterial glycerol fell by 50 per cent and was accompanied by a comparable fall in splanchnic uptake. It is concluded that in normal, postabsorptive man, (a) the major portion of a 100 gm. oral glucose load is retained within the splanchnic bed; (b) only 15 per cent of the ingested glucose is available for disposal by peripheral tissues as increased (above-basal) glucose utilization; (c) the height and shape or the oral glucose tolerance curve are largely determined by the rate and pattern of splanchnic glucose escape; (d) glucose-induced hyperlactatemia, hyperpyruvicemia and hyperalaninemia are due at least in part, to altered splanchnic exchange of these substrates.