A B S T R A C T The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal functioin and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normial subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted.In patients with chronic renal insufficiency (a) the renal uptake ofphenylalanine and the release oftaurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80-90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60-70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.
Muscle protein turnover and amino acid (AA) exchange across the forearm were studied in nine postabsorptive patients with chronic renal failure (CRF) under unrestricted calorie-protein diets and eight controls by using the arterio-venous difference technique associated with the 3H-phenylalanine kinetics. In patients with CRF: (1) the rate of appearance (Ra) of phenylalanine (Phe) from the forearm, reflecting proteolysis, was 27% increased in comparison with controls (P < 0.01). Also the rate of disposal (Rd) of Phe, reflecting protein synthesis, was increased in patients (P < 0.01). As a consequence of these counterbalanced alterations, net balance of Phe across the forearm, that is, net proteolysis, was not changed. (2) The release of total AA from the forearm was not different from controls. Valine and ketoisocaproate release was reduced (P < 0.05). Serine uptake was not detectable. (3) Net proteolysis and the Rd/Ra ratio were inversely and directly, respectively, related to arterial [HCO3-] (P < 0.02 and P < 0.03, respectively). (4) Moreover, net proteolysis and Phe Rd/Ra ratio were directly and inversely, respectively, correlated with plasma cortisol (P < 0.01 and < 0.005, respectively). Plasma cortisol was in the normal range and inversely related to arterial [HCO3-] (P < 0.02). (5) While in controls phenylalanine appearance from the forearm was inversely related to insulin levels, no correlation was found in patients. In conclusion, in patient with CRF, forearm Phe kinetics indicate the existence of an increased muscle protein turnover. Changes in protein synthesis and degradation are well balanced and net proteolysis is not augmented.(ABSTRACT TRUNCATED AT 250 WORDS)
The rate of kidney protein turnover in humans is not known. To this aim, we have measured kidney protein synthesis and degradation in postabsorptive humans using the arterio-venous catheterization technique combined with 14 C-leucine, 15 N-leucine, and 3 H-phenylalanine tracer infusions. These measurements were compared with those obtained across the splanchnic bed, the legs ( Ϸ muscle) and in the whole body. In the kidneys, protein balance was negative, as the rate of leucine release from protein degradation (16.8 Ϯ 5.1 mol/min и 1.73 m 2 ) was greater ( P Ͻ 0.02) than its uptake into protein synthesis (11.6 Ϯ 5.1 mol/min и 1.73 m 2 ). Splanchnic net protein balance was Ϸ 0 since leucine from protein degradation (32.1 Ϯ 9.9 mol/min и 1.73 m 2 ) and leucine into protein synthesis (30.8 Ϯ 11.5 mol/min и 1.73 m 2 ) were not different. In the legs, degradation exceeded synthesis (27.4 Ϯ 6.6 vs. 20.3 Ϯ 6.5 mol/min и 1.73 m 2 , P Ͻ 0.02). The kidneys extracted ␣ -ketoisocaproic acid, accounting for Ϸ 70% of net splanchnic ␣ -ketoisocaproic acid release. The contributions by the kidneys to whole-body leucine rate of appearance, utilization for protein synthesis, and oxidation were Ϸ 11%, Ϸ 10%, and Ϸ 26%, respectively; those by the splanchnic area Ϸ 22%, Ϸ 27%, and Ϸ 18%; those from estimated total skeletal muscle Ϸ 37%, Ϸ 34%, and Ϸ 48%. Estimated fractional protein synthetic rates were Ϸ 42%/d in the kidneys, Ϸ 12% in the splanchnic area, and Ϸ 1.5% in muscle. This study reports the first estimates of kidney protein synthesis and degradation in humans, also in comparison with those measured in the splanchnic area, the legs, and the whole-body.
Renal metabolism of C-peptide was studied in nine nondiabetic nonobese patients with normal renal function by the arterial-venous difference technique before and after the oral administration of an amino acid mixture simulating an animal protein meal. In the basal state, the kidney removed 25.7 +/- 7.5% (+/- SD) of the arterial plasma C-peptide. Renal uptake was approximately 7-fold greater than urinary excretion, and thus, more than 85% of the amount extracted was metabolized by the kidney. Renal C-peptide clearance was very high and approximated the glomerular filtration rate, whereas urinary C-peptide clearance was only 14% of its renal clearance. Shortly after amino acid ingestion, arterial C-peptide levels increased by 107%, and C-peptide renal fractional extraction, uptake, and net metabolism also increased markedly (67%, 278%, and 328%, respectively); urinary clearance and excretion did not change. Renal clearance became 2-fold greater than the glomerular filtration rate, indicating that in this phase the kidney removed substantial amounts of C-peptide from peritubular blood as well as by filtration. Both renal uptake and urinary excretion of C-peptide were related to its arterial levels (P less than 0.001 and P less than 0.05, respectively), but renal uptake increased much more than urinary excretion for each increment in arterial C-peptide levels. These results indicate that renal C-peptide metabolism is considerable in the postabsorptive state and is even more marked during the postprandial period. The kidney, therefore, plays a key role in both the regulation of circulating plasma levels and the metabolic clearance of C-peptide.
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