ABSTRACT
The kinase enzyme is responsible for phosphorylating the enzyme branched chain keto acid dehydrogenase. This phosphorylation downregulates the activity of the enzyme; so, its deficiency leads to very robust dehydrogenase activity. This increased oxidation of the branched chain amino acids leads to very low concentrations of the branched chain amino acid leucine isoleucine and valine, in the blood and cerebrospinal fluid. Levels of threonine, phenylalanine, tyrosine, histidine, and methionine were high. In the mouse model, animals raised on diets enriched in branched chain amino acids were phenotypically normal, and animals without the enrichment had seizures and neurologic abnormalities that could be abolished by enrichment of the diet. Branched chain amino acids are transported across the blood–brain barrier by the amino acid L-type transporter pathway shared by other large neutral amino acids. In the mice, levels of the branched chain amino acids were low in brain.
