Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation

J Inherit Metab Dis. 2000 Dec;23(8):805-18. doi: 10.1023/a:1026708618507.

Abstract

We characterized the effect of orthotopic liver transplantation on the catabolism of branched-chain L-amino acids in a female patient with classical form of maple syrup urine disease. Transplantation was performed at the age of 7.4 years due to a terminal liver failure triggered by a hepatitis A infection. Since then, the patient is on an unrestricted diet and plasma concentrations of branched-chain L-amino and 2-oxo acids are stable, yet at moderately increased levels (2- to 3-fold of control). L-Alloisoleucine concentrations, however, remained remarkably elevated (> 5-fold of control). In vivo catabolism was investigated by measuring the metabolic L-alloisoleucine clearance and whole-body leucine oxidation in the postabsorptive state. In an oral loading test with 580 micromol alloisoleucine per kg body wt, the L-alloisoleucine elimination rate constant (0.067 h(-1)) was in the normal range (0.069+/-0.012 h(-1), n = 4). In an oral L-[1-13C]leucine load (38 micromol/kg body wt), 19.5% of the tracer dose applied was recovered in exhaled 13CO2 versus 18.9+/-3.6% in healthy subjects (n = 10). Thus, the patient exhibited obviously normal whole-body catabolic rates although branched-chain L-amino acid oxidation was confined to the liver transplant. Most likely, the enhanced substrate supply from extrahepatic sources led to an elevation of the plasma concentrations and thus induced a compensatory enhancement of the metabolic flux through the branched-chain 2-oxo acid dehydrogenase complex in the intact liver tissue.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Female
  • Humans
  • Isoleucine / metabolism*
  • Leucine / metabolism*
  • Liver Transplantation*
  • Maple Syrup Urine Disease / blood
  • Maple Syrup Urine Disease / metabolism*
  • Oxidation-Reduction

Substances

  • Isoleucine
  • Leucine