Hormone-fuel concentrations in anephric subjects. Effect of hemodialysis (with special reference to amino acids).

331

147

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.

Section: Discussionsupporting

confidence: 81%

Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.

Tizianello¹,

Ferrari²,

Garibotto³

et al. 1980

331

147

“…Amino acids such as glutamate, serine, and the branched-chain amino acids appeared to be increased 30-50% in anephric patients, compared to normal volunteers (12)(13)(14)(15), whereas other amino acids such as glutamine, citrulline, glycine, and the methyl histidines were substantially increased in uremic subjects (12)(13)(14)(15)(16). Although blood levels of other amino acids such as aspartate, threonine, histidine, and particularly alanine were found to be unchanged, plasma levels of alanine, aspartate, and threonine were increased in anephric subjects (12)(13)(14)(15)(16). Recently we observed a patient with chronic uremia and episodes of spontaneous hypoglycemia in whom hypoalaninemia and decreased rates of gluconeogenesis from alanine were found to account, at least in part, for the pathogenesis of the hypoglycemia (17).…”

Section: Introductionmentioning

confidence: 87%

“…Diverse alterations of blood amino acid levels have been described in uremic patients maintained on hemodialysis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Amino acids such as glutamate, serine, and the branched-chain amino acids appeared to be increased 30-50% in anephric patients, compared to normal volunteers (12)(13)(14)(15), whereas other amino acids such as glutamine, citrulline, glycine, and the methyl histidines were substantially increased in uremic subjects (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Skeletal Muscle Protein and Amino Acid Metabolism in Experimental Chronic Uremia in the Rat

Garber¹

1978

“…Blood alanine levels have been observed to be unaltered, increased, or decreased (5,6). These disparate observations prompted an investigation of alanine and glutamine metabolism and release from skeletal muscle of experimentally uremic rats.…”

Section: Introductionmentioning

confidence: 99%

“…Cyclic AMP was determined in trichloroacetic acid extracts of muscle by double-antibody radioimmunoassay (21). Adenylate cyclase activities were determined in a 50-1,u final volume containing (unless otherwise specified) 3.0 mM [a-32P]ATP (2)(3)(4) IuM), 5.0 mM MgCl2, 1 mM EDTA, 1 mM [3H]cAMP ("10,000 cpm), 24 mM bis-tris-propane-HCI buffer (pH 7.5), and an ATP-regenerating system consisting of 20 mM creatine phosphate, 0.2 mg/ml creatine phosphokinase, and 0.02 mg/ml myokinase and up to 20 ,ul of homogenate of 10,000 g particles 50-75 ,ug protein). When present, epinephrine was 10 ,uM and NaF was 10 mM.…”

Section: Introductionmentioning

confidence: 99%

The Regulation of Skeletal Muscle Alanine and Glutamine Formation and Release in Experimental Chronic Uremia in the Rat

Garber¹

1978

A B S T R A C T The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 ,uM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 ,uM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO2 was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two-to fourfold or more in control than in uremic muscle. Basaland fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10lM epinephrinestimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 usM), the stimulation of membrane adenylate cyclase activity was one-to twofold greater with control membranes than with uremic muscle Dr. Garber is an investigator ofthe Howard Hughes Medical Institute.