Kidney, splanchnic, and leg protein turnover in humans. Insight from leucine and phenylalanine kinetics.

Abstract

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 amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

“…In addition, our data demonstrated that the kidney participates in leucine transamination; in all three groups studied reamination and deamination rates consistently ranged from 6 to 12 μmol/min, corresponding to between 10 and 20% of whole-body transamination under conditions of wellcontrolled insulin. These findings are in contrast to the previous study [13], which reported renal transamination rates below zero. The discrepancy could relate to the different patient categories studied, because it cannot be excluded that patients with hypertension and cardiac disease may have subtly compromised renal function.…”

“…The finding that 5-10% of wholebody phenylalanine and leucine fluxes occur across the renal bed is in line with a previous study [13], which reported a renal component of 10% in patients with hypertension and cardiac disease. In addition, our data demonstrated that the kidney participates in leucine transamination; in all three groups studied reamination and deamination rates consistently ranged from 6 to 12 μmol/min, corresponding to between 10 and 20% of whole-body transamination under conditions of wellcontrolled insulin.…”

“…Glucose concentrations were monitored throughout the night. Between 07.30 and 08.30 h the following morning cannulas were placed in the femoral vein, one renal vein and the femoral artery, as described previously [6,13,16,17]. Renal vein catheters were inserted under fluoroscopic guidance; the femoral artery line was used for infusion of indocyanine green (0.6 mg/min) to measure blood flow in the leg and for blood sampling.…”

“…It was additionally found that deamination of leucine to ketoisocaproate (KIC) and reamination of KIC to leucine was increased five-fold during insulin deprivation, but the tissues responsible for this phenomenon were not identified. A recent report used renal vein catheterisation and radioactive amino acid tracers and demonstrated that in non-diabetic postabsorptive humans 25% of leucine oxidation and around 10% of leucine appearance and leucine protein synthesis took place in the kidney [13]. The kidney has also been shown to be a major site of phenylalanine conversion to tyrosine and a contributor of tyrosine to the circulation [14].…”

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

“…We previously evaluated protein turnover across the human kidney in studies on the basis of the organ mass balance associated with leucine isotope kinetics (14,15). Kidney protein turnover, as compared with muscle and splanchnic turnover, is characterized by the highest rates of protein synthesis and amino acid oxidation.…”