Quantifying rates of protein synthesis in humans by use of 2H2O:: application to patients with end-stage renal disease

A method is introduced for quantitating protein synthetic rates in humans by use of (H2O)-H-2. Its validity was tested in subjects with end-stage renal disease. Six clinically stable subjects, hemodialyzed three times weekly, ingested (H2O)-H-2 to a body water H-2 enrichment of similar to0.4%. On dialysis, body water enrichment declined to similar to 0.1%. Enrichment of the alpha-hydrogen of plasma free alanine was also similar to0.4% before and similar to 0.1% after dialysis. beta-Hydrogen enrichment was similar to80-100% of alpha-hydrogen enrichment. (H2O)-H-2 was ingested to replace (H2O)-H-2 removed after each dialysis for 15 - 51 days, returning enrichment to similar to0.4%. Enrichment of alanine from plasma albumin gradually increased, with again similar to 80 - 100% as much H-2 in beta- as in alpha-hydrogens. With continued dialyses, without (H2O)-H-2 replacement, alanine from albumin enrichment gradually declined, whereas free alanine and water enrichments were negligible. The fractional albumin synthesis rate, calculated from the increase in enrichment in alanine from albumin, was 4.0 +/- 0.5%/day, and from the decrease, 4.6 +/- 0.2%/day. Thus body water enrichment in a subject given (H2O)-H-2 can be maintained constant long term. A rapid exchange, essentially complete, occurs between the hydrogens of alanine and body water. An integrated measure over a long period of albumin's synthetic rate can be estimated from both the rise in enrichment of alanine from the protein during (H2O)-H-2 ingestion and fall on (H2O)-H-2 withdrawal, while the subject's living routine is uninterrupted. Estimates are in subjects with renal disease, but the method should be applicable to estimates of protein synthetic rates in normal subjects and in other pathological states.