BETA-HYDROXYBUTYRATE DECREASES ADENOSINE-TRIPHOSPHATE DEGRADATION PRODUCTS IN HUMAN-SUBJECTS

Many disease states decrease intracellular adenosine triphosphate (ATP ) levels and elevate body fluid purine levels. The use of specific met abolic substrates may reverse this process. This study was designed to test the hypothesis that beta-hydroxybutyrate, a substrate for ATP sy nthesis, decreases body fluid purine levels during interventions that induce ATP degradation. Decreases in these purine levels are metabolic markers for diminished ATP degradation. Two human models for stimulat ing ATP degradation were used to test the hypothesis. Rapid fructose i nfusion causes acute degradation of hepatic ATP, and ischemic exercise stimulates ATP consumption in skeletal muscle. The activity of beta-h ydroxybutyrate was used in combination with phosphate, another importa nt substrate for ATP synthesis. The studies were performed during a lo w-phosphate state in 10 normal subjects and during a high-phosphate st ate in 7 normal subjects. Metabolic variables, such as serum or urinar y phosphate level, blood beta-hydroxybutyrate level, blood acetoacetat e level, plasma or urinary purine level, blood lactate level, and bloo d ammonia level, were monitored during the study. After ischemic exerc ise of the forearm muscle, beta-hydroxybutyrate decreased the level of plasma total purines, blood lactate, and blood ammonia during the low -phosphate state but not during the high-phosphate state. During fruct ose-induced hepatic ATP breakdown, beta-hydroxybutyrate decreased late phase plasma purine increases under low-phosphate conditions only and decreased urinary total and radiolabeled purine elevations under both phosphate conditions. These data indicate that the infusion of beta-h ydroxybutyrate may alter the balance from ATP degradation toward ATP r esynthesis in muscle and liver by providing an immediate source of fue l and reducing equivalents under under specific metabolic conditions. This activity in combination with other metabolic interventions may ha ve therapeutic value by restoring ATP pools in ATP-depleted tissues.