Quantifying rates of protein synthesis in humans by use of2H2O: application to patients with end-stage renal disease

Abstract

A method is introduced for quantitating protein synthetic rates in humans by use of2H2O. Its validity was tested in subjects with end-stage renal disease. Six clinically stable subjects, hemodialyzed three times weekly, ingested2H2O to a body water2H enrichment of ∼0.4%. On dialysis, body water enrichment declined to ∼0.1%. Enrichment of the α-hydrogen of plasma free alanine was also ∼0.4% before and ∼0.1% after dialysis. β-Hydrogen enrichment was ∼80-100% of α-hydrogen enrichment.2H2O was ingested to replace2H2O removed after each dialysis for 15-51 days, returning enrichment to ∼0.4%. Enrichment of alanine from plasma albumin gradually increased, with again ∼80-100% as much2H in β- as in α-hydrogens. With continued dialyses, without2H2O 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 given2H2O 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 during2H2O ingestion and fall on2H2O 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.