Copyriglil O 1995 International Pediatric Research Foundation, Inc.
Vol. 37, No. 4, 1995
l'nnied in U.S.A.
Whole-Body Protein Turnover in Preterm
Appropriate for Gestational Age and Small for
Gestational Age Infants: Comparison of
[ ' * ~ ] ~ l ~ c i n e and [ ~ - ' ~ ~ ] ~ e u c i n e
J. B. VAN GOUDOEVER, E. J. SULKERS, D. HALLIDAY, H. J. DEGENHART, V. P. CARNIELLI,
J. L. D. WATTIMENA, AND P. J. J. SAUER
Department of Paediatrics [J.B. V. G., E. J.S., H.J.D., V. P. C., J.L.D. W.,
Rotterdam/Sophia Children's Hospital, Erasmus University Rotterdam, The Netherlands, and
Clinical Research Centre [D.H.], Harrow, London, United Kingdom
P. J. J.S.], Academic Hospital
Measurements of whole-body protein turnover in preterm
infants have been made using different stable isotope methods.
Large variation in results has been found, which could be due to
different clinical conditions and/or the use of different tracers.
We studied 14 appropriate for gestational age and nine small for
gestational age orally fed preterm infants using ['"]glycine
[l-"C]leucine simultaneously, which allowed us to make a
comparison of commonly used methods to calculate whole-body
protein turnover. Whole-body protein turnover was calculated
from '% enrichment in urinary ammonia and urea after [I5N]-
glycine administration and from the "C enrichment in expired
CO, after administration of [l-'"]leucine.
toisocaproic acid after [l -l"]leucine
sured as a direct parameter of whole-body protein turnover.
Group means for whole-body protein turnover using ['5N]gly-
cine or [l-13C]leucine ranged from 10 to 14 g.kgP'.dP1, except
when using the end product method that assumes a correlation
Enrichment of a-ke-
constant infusion was mea-
The use of stable isotopes for measuring metabolic processes
in vivo has a clear ethical advantage over radioactive isotopes.
The nonradioactive character allows their use in pregnancy and
in infants. Schoenheimer et al. (1) used stable isotopes to study
protein turnover as early as 1939, but more extensive research
has been done since the 1970s, when analytical techniques
improved remarkably (2). From then onward, numerous pro-
tein turnover studies have been performed using stable iso-
topes, in adults as well as in children. 15~-labeled amino acids
have been favored for many years in preterm infants because of
the noninvasive character of the studies. The method allows
Received Junc 25, 1994; accepted Dccc~nhcr 8, 1994.
Corrcspondence: J. B. Van Goudoever, M.D., Ph.D., Sophia Childrens Hospital, Dr.
Molewlitcrplcin 60, 3015 GJ Rotterdam, The Netherlands.
Supported by the Netlicrlands Organization for Scientific Research (NWO) (J.B.V.G.).
I Manuscriut dedicated to Professor M. K. A. Visser in honor of his rctlrement.
between leucine oxidation and total nitrogen excretion. We found
very low '% enrichment of urinary urea in the majority of small
for gestational age infants. These infants also had a lower
nitrogen excretion in urine and oxidized less leucine. Nitrogen
balance was higher in small for gestational age infants (41 6 ? 25
mg.kgP1.dP') compared with appropriate for gestational age
infants (374 ? 41 mg.kgP'.dP', p = 0.003). [I5~]Glycine does
not seem to exchange its label with the body nitrogen pool to a
significant degree and is therefore not always suitable as a carrier
for 15N in protein turnover studies in premature infants. (Pediatr
Res 37: 381-388, 1995)
AGA, appropriate for gestational age
SGA, small for gestational age
KICA, ketoisocaproic acid
IRMS, isotopic ratio mass spectrometer
quantification of protein metabolism by measurement of iso-
tope enrichment in an end product of protein catabolism in
urine (3-10). [1 -l"]~eucine, another stable isotopic labeled
tracer, has been used for protein studies in preterm neonates
more recently, with either the measurement of isotopic enrich-
ment of [l-13~]leucine or ['
plasma (13-17). The different tracers give different results, i.e.
for whole-body protein synthesis, rates ranging from 5
g.kg-l.d-' to 26 g.kg-'.d-' have been reported, depending
on clinical and experimental conditions (3, 14). Studies were
performed comparing different tracers and amino acids in
adults (18) and in term infants (19) or comparing different
amino acids with a similar label (8, 9, 20). However, to date
there are no studies comparing the two most commonly used
labeled amino acids, [I5~lglycine and [l-'%]leucine, in pre-
3~]~-~~~~ in urine (11, 12) or
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