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1 Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA
2 Department of Nephrology, Cleveland Clinic Foundation, Cleveland, OH, USA
3 Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
4 Department of Mathematics, Case Western Reserve University, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: brl{at}cwru.edu.
A method is introduced for quantitating protein synthetic rates in humans using 2H2O. Its
validity was tested in subjects with end stage renal disease. Six clinically stable subjects,
hemodialyzed three times weekly, ingested 2H2O to a body water 2H enrichment of ~0.4%. On
dialysis body water enrichment declined to ~0.1%. Enrichment of the
hydrogen of plasma free
alanine was also ~0.4% before and ~0.1% after dialysis.
hydrogen enrichment was ~80 to
100% of
hydrogen enrichment. 2H2O was ingested to replace 2H2O removed after each dialysis
for 15 to 51 days, returning enrichment to ~0.4%. Enrichment of alanine from plasma albumin
gradually increased, with again ~80 to 100% as much 2H in
as
hydrogens. With continued
dialyses, without 2H2O replacement, alanine from albumin enrichment gradually declined, while
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 2H2O 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 2H2O ingestion and fall on 2H2O 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.
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