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1 Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
2 Department of Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
3 Albuquerque Academy, Albuquerque, NM, USA
4 Division of Epidemiology and Preventive Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
5 Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA
* To whom correspondence should be addressed. E-mail: draj{at}salud.unm.edu.
Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls using stable isotopes of phenylalanine, alanine and glutamine. The amino acid transport kinetics and protein turnover were calculated with a 3-pool model from the amino acid concentrations and enrichment in the artery, vein and muscle compartments. Muscle protein breakdown was more than synthesis (nmol/min-1.100 ml leg-1) during hemodialysis (HD) (169.8±20.0 vs. 125.9±21.8, p<0.05) and in controls (126.9±6.9 vs. 98.4±7.5, p<0.05), but synthesis and catabolism were comparable pre-HD (100.7±15.7 vs. 103.4±14.8). The whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0±47.1 vs. 243.0±34.689) and glutamine (369.7±40.6 vs. 235.6±27.5) from muscle protein breakdown increased during dialysis (nmol/min-1.100 ml leg-1,p<0.01). However, the de novo synthesis of alanine (3468.9 ±572.2 vs. 3140.5±467.7) and glutamine (1751.4±82.6 vs. 1782.2±86.4) did not change significantly intra-dialysis (nmol/min-1.100 ml leg-1). Branched chain amino acid catabolism (191.8±63.4 vs. -59.1±42.9) and non-protein glutamate disposal (347.0±46.3 vs. 222.3±43.6) increased intra-dialysis compared to pre-HD (nmol/min-1.100 ml leg-1, p<0.01). The mRNA levels of glutamine synthase (1.45±0.14 vs. 0.33±0.08, p<0.001) and branched chain keto acid dehydrogenase-E2 (3.86±0.48 vs. 2.14±0.27, p<0.05) in the muscle increased during HD. Thus, intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. While muscle protein breakdown increased intra-dialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.
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