Acetone Bodies

ACETONE BODIES, a name that combines acetone, acetoacetic acid, and beta-hydroxybutyric acid into one group, due to the commonality of their formation in the body, the mutual chemical relationship of these three substances, and the ease with which they transform into one another. Acetone (see) is cleaved from acetoacetic acid and is excreted through the lungs and kidneys in any case of ketonuria. The amount of acetone in urine is always small, and if analyses frequently mention significant quantities of this substance, it is only because all reactions for acetone are also given by acetoacetic acid. When quantitative determinations give the amount of acetone in urine, this also includes the acetone that was cleaved from acetoacetic acid during the analysis. As for beta-hydroxybutyric and acetoacetic acids, which differ chemically from each other only by 2 hydrogen atoms [CH₃.CO.CH₂.COOH and CH₃CH(OH).CH₂.COOH], these two bodies undoubtedly transform into one another within the organism, and in the urine of animals, beta-hydroxybutyric and acetoacetic acids appear equally when either beta-hydroxybutyric or acetoacetic acid is introduced into the blood. From this it follows that the chemical pathway from acetoacetic acid to beta-hydroxybutyric acid can be traversed in both directions within the organism. This circumstance greatly complicates the question of which of these acetone bodies is formed earlier in metabolism. By quantity, beta-hydroxybutyric acid is always excreted in urine in greater amounts than acetoacetic acid. The material for the formation of acetone bodies is provided, mainly, by fatty acids originating from fat deposits. These acids are broken down sequentially by oxidation at the beta-carbon atom, and those with an even number of carbon atoms in the straight chain yield beta-hydroxybutyric acid: for example, CH₃.CH₂.CH₂.CH₂...CH₂.COOH → CH₃.CH₂.CH₂.COOH → CH₃.CH(OH).CH₂.COOH. But amino acids, particularly those containing an odd number of carbon atoms in the straight chain, can also yield acetone bodies, with cleavage occurring at the alpha-carbon atom, resulting in fatty acids with an even number of carbon atoms in the straight chain; for example, CH₃.CH₂.CH₂.CH(NH₂).COOH → CH₃.CH₂.COOH → CH₃.CH(OH).CH₂.COOH. Minkowski and some other authors consider acetone bodies as intermediate products in the formation of carbohydrates from fats in the body. There are indications of the possibility of acetone body formation in the body by synthesis from acetaldehyde through aldol (see) or crotonic acid CH₃CH::CH.COOH. The liver undoubtedly plays a major role in the process of ketone body formation: an enzyme has been described that causes the transformation of acetoacetic acid into beta-hydroxybutyric acid and the reverse reaction; acetone bodies formed in metabolism can be detected in the blood and organs. Normal blood contains 3-5 mg% of acetone. In acidosis, its content increases 10 or more times. Acetone bodies are excreted in urine in various cases: in severe diabetes, during fasting, with protein-fat nutrition, during fever, during pregnancy, after surgical operations and anesthesia, etc. Since both substances—acetoacetic and beta-hydroxybutyric acids—are acidic in nature, their accumulation in the body leads to acidosis (see). There are many severe conditions in which ketonuria occurs. But how great the participation of acetone bodies in poisoning is in these cases is far from clear, even in relation to diabetic coma. On the other hand, ketonuria often lasts for years without any harmful consequences. It is not always possible to successfully combat ketonuria. It is recommended to remember that ketonuria develops easily in the absence of carbohydrates and excessive abundance of proteins and fats in food. The best way to inhibit the formation of ketone bodies is to give the patient more carbohydrates without simultaneously introducing proteins. In cases of diabetic ketonuria, excellent results are often noted from the simultaneous use of insulin (see), up to 100 or more units per day. Many authors believe that in other cases of ketonuria, the use of insulin is also successful. However, it remains controversial how necessary combating ketonuria as such is. In many cases, attention should rather be directed to the causes that produce it, after the elimination of which ketonuria also disappears.