AJP - Endocrinology and Metabolism, Vol 258, Issue 4 E654-E660, Copyright © 1990 by American Physiological Society
Protein and leucine metabolism in maple syrup urine disease
G. N. Thompson, J. L. Bresson, P. J. Pacy, J. P. Bonnefont, J. H. Walter, J. V. Leonard, J. M. Saudubray and D. Halliday
Nutrition Research Group, Clinical Research Centre, Harrow, United Kingdom.
Constant infusions of [13C]leucine and [2H5]phenylalanine were used to
trace leucine and protein kinetics, respectively, in seven children with
maple syrup urine disease (MSUD) and eleven controls matched for age and
dietary protein intake. Despite significant elevations of plasma leucine
(mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein
synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/-
0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50,
respectively). The relationship between phenylalanine and leucine fluxes
was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio
0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02).
Leucine oxidation was undetectable in four of the MSUD subjects and very
low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These
results show that persistent elevation in leucine concentration has no
effect on protein synthesis. The marked disturbance in leucine metabolism
in MSUD did not alter the relationship between rates of catabolism of
protein to phenylalanine and leucine, which provides further support for
the validity of the use of a single amino acid to trace whole body protein
metabolism. The minimal leucine oxidation in MSUD differs from findings in
other inborn metabolic errors and indicates that in patients with classical
MSUD there is no significant route of leucine disposal other than through
protein synthesis.
