We plan to explore the molecular basis of the seeming exception to the one gene-one enzyme concept presented by the human hereditary disease, branched-chain Ketoaciduria (Maple Syrup Urine Disease). These patients show a gross deficiency in the ability to decarboxylate all of three of the branched-chain-alpha-ketoacids, alpha-ketoisovaleric, alpha-ketoisocaproic, and alpha-keto-beta-methylvaleric. We plan also to purify the enzyme(s) and study their kinetics, specificities, structure, etc., in detail. The effects of relatively large amounts of the various cofactors involved will also be studied in vitro and in vivo in an attempt to find a treatment to complement or replace the extensive and difficult dietary regimen now in use for the control of clinical manifestations of branched - chain ketoaciduria. A study will be made of the possibility of producing an experimental model of the hereditary metabolic disorder, branched-chain ketoaciduria (or Maple Syrup Urine Disease) in rats by administration of antagonists of the corresponding amino or ketoacids.