The Renal Tubular Response to Amino Acid Loading 1

Abstract

In previous studies from this laboratory (1) it was shown that renal tubular reabsorption of filtered amino acids was virtually complete in the fasting state. However, when a solution of amino acids was administered intravenously and the load filtered by the kidney thus increased, both the amounts of amino acids reabsorbed and those excreted were increased. In quantitative terms the more noteworthy event was the increase in amount reabsorbed. Considerable selectivity was exhibited in the reabsorption of individual amino acids and evidence was obtained which was interpreted as indicating a "competition" for reabsorption between cystine and one or more other amino acids.In the present studies the solution of amino acids used for loading was administered at a faster rate than in the previously reported experiments and it was supplemented with additional glycine to test the effects of a further increase in the filtered load of amino acids. In separate studies glycine was administered alone and, in terms of amounts reabsorbed and excreted, the results were compared with those obtained when glycine was given as part of the amino acid mixture and comparable filtered loads were achieved. METHODSThree normal subjects-DNW (age 21, ht. 184.2 cm., wt. 85.5 kg.), WRR (age 28, ht. 175.3 cm., wt. 95.0 kg.), and WS (age 29, ht. 168.9 cm., wt. 60.5 kg.)-were given Merck's 10 per cent solution of free amino acids. The experimental protocol is outlined in Table I-A, the rate of infusion being calculated on a basis of its glycine content. The glomerular filtration rate (GFR) was meas-

Renal Tubular Transport of Proline, Hydroxyproline, and Glycine in Health and in Familial Hyperprolinemia *

“…4) In our experiments there were increases in clearance rates produced by the infusion of imino acids and glycine affecting amino acids beyond the limits of the hypothetical "common" transport system. Whereas glycine infusion had little effect on imino acid excretion, it increased clearance rates of serine and threonine, in addition to raising the plasma concentration of serine; this phenomenon has also been noted by others (40). Infusion of either imino acid increased clearance rates of serine, threonine, a-amino-n-butyric acid, and the aromatic amino acids in later postinfusion periods.…”

Toxicity and Blood Ammonia Rise Resulting from Intravenous Amino Acid Administration in Man: The Protective Effect of l-Arginine

“…Although the authors attributed the marked blood ammonia rise to deamination of the D-amino acids, it is now appreciated that ammonia may also be an intermediate in L-amino acid metabolism. Ammonia formation in man was postulated by Doolan to explain the toxic effects he observed with rapid glycine infusion (10). His normal fasting subject experienced malaise, nausea, vomiting and a pyrogenic-type reaction with marked weakness, shaking chills, headaches and temperature to 100.80 F. Blood ammonia levels were not measured in Doolan's patient nor in our patient who developed coma without marked nausea or vomiting, although narcotic administration may have suppressed these manifestations in the latter instance.…”

“…Intravenous amino acid administration has been utilized as a liver function test (20)(21)(22) and in renal tubular function studies (10), and intravenous glycine has been proposed as a means of combating hypothermia (23 given, the ammonia-forming characteristics of the amino acid(s) infused, and the state of nutrition of the host, particularly in relation to recent arginine intake. 3.…”

Apparent Free Amino Acids in Deproteinized Plasma of Normal and Uremic Persons1

“…Intravenously administered arginine is not very toxic (13) (15) have reported similar findings in two patients. Glycine is known to cause potassium extrusion when added to media containing suspended cells (16), and to cause severe toxic effects when administered intravenously to dogs (17) and humans (18). An investigation of the role of the glycine molecule in uremia appears indicated.-It is not believed that a toxic effect of elevated plasma glycine levels in uremia is due to the increase in free plasma ammonia which has been observed following glycine infusions in dogs and patients (17).…”