Found in all organisms, the alpha-keto acid dehydrogenase complexes have central roles in cellular metabolism and are major sites of regulation. The understanding of the organization, function and regulation of these quintessential multienzyme complexes has been greatly advanced by studies employing molecular biology and biophysical techniques. Although these enzyme systems have some features in common, their diversity in fulfilling unique organism - or tissue - specific roles is truly amazing. These systems have medical importance in areas ranging from defects in regulation (linked to...

HISTORICAL BACKGROUND The use of genetic animal models in neuroscience and biomedical research is showing dramatic growth. The earliest application of these models to research on drug mechanisms was in the area of alcohol research. Mardones (1951) reported successful selective breeding of rats preferring and not preferring to drink alcohol under various conditions of dietary deficiency, suggesting genetic control of alcohol drinking. McClearn and Rodgers (1959, 1961) described differences among inbred mouse strains in preference for 10Ofo ethanol solutions versus tap water. Active exploration...