DEVELOPMENT OF AN ANIMAL-MODEL FOR MAPLE SYRUP URINE DISEASE BY DIETARY BRANCHED-CHAIN AMINO-ACIDS AND TREATMENT WITH BETA-CHLOROALANINE, AN ALPHA-KETO ACID DEHYDROGENASE INHIBITOR

Feeding the rats with an additional 5% valine for a week increased the serum level of valine, leucine, and iso-leucine by 27, 8, and 10 fold respectively. Beta-chloroalanine (an alpha-keto acid decarboxylase inhibitor) treatment further enhanced the serum levels of valine, leucine and iso-leucine 4, 2, and 2 fold respectively. Feeding 5% additional leucine for a week enhanced the serum levels of valine, leucine, and iso-leucine by 7, 19, and 7 fold respectively. Beta-chloroalanine treatment did not further change the serum levels of these amino acids in this group. An additional 5% dietary iso-leucine raised the serum levels of valine leucine, and iso-leucine by 9, 9, and 54 fold respectively. Beta-chloroalanine treatment further enhanced the serum level of valine and iso-leucine by 2 and 1.6 fold respectively. Treating control animals with beta-Chloroalanine raised the serum levels of valine, leucine, and iso-leucine by 2, 3, and 3 fold respectively. The rats treated with beta-Chloroalanine lost weight and about 20% of the animals died. An animal model of Maple Syrup Urine Disease may be developed by feeding the animals branched-chain amino acids along with a treatment with beta-Chloroalanine.