Much information has come to light in recent years which bears on the problem of why ketone bodies accumulate in the mammalian body under certain conditions. I propose to discuss in this lecture observations which lead to the concept that ketosis is a disorder of the regulation of metabolic processes rather than an insufficiency of certain enzymes or of key metabolites.
Let me first recall the main biochemical facts concerning the accumulation of ketone bodies. It is now firmly established that the bulk of the ketone bodies arises by condensation of acetate which reacts in the form of acetyl coenzyme A (Scheme 1). It is also firmly established that all foodstuffs—not only fats but also carbohydrates and proteins—yield acetyl coenzyme A when they are burned in the body, and are therefore potential sources of ketone bodies. Acetyl coenzyme A can enter many metabolic reactions, but quantitatively the most important one