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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 β-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 ischemie exercise stimulates ATP consumption in skeletal muscle. The activity
of β-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 β-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, β-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, β-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 β-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.
Abbreviations:
AMP (adenosine monophosphate), ATP (adenosine triphosphate), CoA (coenzyme A), CRC (University of Michigan Clinical Research Center), NADH (reduced nicotinamide adenine dinucleotide), Pi (inorganic phosphate)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
February 18,
1994
Received in revised form:
February 15,
1994
Received:
January 22,
1993
Footnotes
☆Supported by Public Health Service Grants 2R01 DK 19674, 5 MO1 RR 42, and 2P60 DKS 20572.
Identification
Copyright
© 1994 Published by Elsevier Inc.
