The Metabolism of Acetate-1- 14 C in the Day-Old Chicken

It has been repeatedly demonstrated that a large variety of animals develop ketosis when their diet contains a high proportion of lipid relative to carbohydrate (1). However, the chick embryo (2) as well as growing chicks (3, 4) can utilize diets essentially devoid of carbohydrates without developing ketosis. Since the enzymes necessary for acetoacetate biosynthesis are demonstrable in chick liver (5) and ketosis can be produced if fatty acids furnish all nonprotein calories (4), the lack of ketosis in the chicken can not be attributed to an inability to synthesize ketone bodies.

Ketosis could be avoided, however, if the chick could perform a net synthesis of carbohydrate from acetate via some pathway which is not physiologically important in other animals (6) but may become important in the developing chick where lipid is the only available energy source. Three possible pathways which could account for a net synthesis of carbohydrate from acetate are: (a) initial synthesis of acetoacetate, which then is converted to a glycolytic intermediate via either acetone (7) or pyruvaldehyde (8), (b) synthesis of butyrate which is converted to succinate by ω-oxidation (9), or (c) synthesis of malate via the glyoxalate bypass (10, 11). The first of these would not only decrease ketone body synthesis by making carbohydrate available, but would also reduce circulating ketone bodies by utilization.

Utilization of acetate by any of these pathways can be distinguished from its oxidation by the classical citric acid cycle by injecting acetate-1-¹⁴C and measuring incorporation of radioactivity into amino acids (12). Using this technique, it was found that acetate is metabolized primarily via the citric acid cycle and that, if any of these special pathways are present in the chick, they are of limited importance.