Branched chain amino acid metabolism: Requirements in healthy adult men and patients with maple syrup urine disease

Based on evidence from a series of stable isotope studies, the dietary recommendations for branched chain amino acids (BCAA), from nitrogen balance studies, are too low. As such the dietary requirement for BCAA has been increased in the new dietary reference intake (DRI) report. To date, stable isotope studies determined the requirement of leucine and valine individually, but not isoleucine.; The requirement for total BCAA was determined by the indicator amino acid oxidation (IAAO) technique in adult men (n = 7) with an oral isotope dosing protocol in which L-[1-₁₃C]phenylalanine was used as an indicator amino acid (IAA). To reduce the possibility of interactions among the branched chain amino acids and imbalances in the mixture affecting the estimate of requirement, we adopted the proportion of BCAA in egg protein. The rate of release of 13CO₂ from the oxidation of L-[1-13C]phenylalanine (F13CO₂) was measured and a two-phase linear regression crossover model applied to determine the requirement for total BCAA. The mean requirement and population safe level (upper limit of 95% Cl) of total BCAA were 144 mg·kg −1·d−1 and 210 mg·kg −1·d−1, respectively.; Once the total BCAA requirement had been determined, it was necessary to define whether any one of the BCAA was limiting. Five subjects, with known total BCAA requirement were restudied. We held constant one of the BCAA at the individual's requirement level, while the other two were reduced by 10% and 20%, in random order. Based on increases in label appearance (F 13CO₂) in response to decreased intake of each of the branched chain amino acids, we concluded that valine is the first limiting branched chain amino acid in egg protein.; Maple syrup urine disease is an inherited disorder results from defects in the mitochondrial multienzyme complex branched chain ketoacid dehydrogenase (BCKD; EC 1.2.4.4). Five classical MSUD patients were assigned to different intakes of total BCAA, using the indicator amino acid oxidation (IAAO) technique. Total BCAA requirement was determined by measuring the oxidation of L-[1- 13C]phenylalanine to 13CO₂ (F13CO ₂). The mean requirement for total BCAA was 45 mg·kg−1 ·d−1 and the safe level of intake (upper 95% confidence interval) was 62 mg·kg−1·d −1.