title: beta-Hydroxybutyrate decreases adenosine triphosphate degradation products in human subjects.
abstract: Many disease states decrease intracellular adenosine triphosphate (ATP) levels and elevate body fluid purine levels. The use of specific metabolic substrates may reverse this process. This study was designed to test the hypothesis that beta-hydroxybutyrate, a substrate for ATP synthesis, 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 stimulating ATP degradation were used to test the hypothesis. Rapid fructose infusion causes acute degradation of hepatic ATP, and ischemic exercise stimulates ATP consumption in skeletal muscle. The activity of beta-hydroxybutyrate was used in combination with phosphate, another important substrate for ATP synthesis. The studies were performed during a low-phosphate state in 10 normal subjects and during a high-phosphate state in 7 normal subjects. Metabolic variables, such as serum or urinary phosphate level, blood beta-hydroxybutyrate level, blood acetoacetate level, plasma or urinary purine level, blood lactate level, and blood ammonia level, were monitored during the study. After ischemic exercise 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 fructose-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-hydroxybutyrate may alter the balance from ATP degradation toward ATP resynthesis in muscle and liver by providing an immediate source of fuel and reducing equivalents under under specific metabolic conditions. This activity in combination with other metabolic interventions may have therapeutic value by restoring ATP pools in ATP-depleted tissues.
authors.affiliation: Department of Internal Medicine, University Hospital, Ann Arbor, Michigan.
authors.forename: B
authors.initials: B
authors.lastname: Lestan
authors.forename: K
authors.initials: K
authors.lastname: Walden
authors.forename: S
authors.initials: S
authors.lastname: Schmaltz
authors.forename: J
authors.initials: J
authors.lastname: Spychala
authors.forename: I H
authors.initials: IH
authors.lastname: Fox
mesh_terms: D020155:3-Hydroxybutyric Acid; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood; D015444:Exercise / Q000502:physiology; D005632:Fructose / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology; D007773:Lactates / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000652:urine; D011687:Purines / Q000097:blood / Q000652:urine
chemical_list: D006885:Hydroxybutyrates; D007773:Lactates; D010710:Phosphates; D011687:Purines; D005632:Fructose; D000641:Ammonia; D000255:Adenosine Triphosphate; D020155:3-Hydroxybutyric Acid