Effects of ketone bodies on amino acid metabolism in isolated rat diaphragm.
Level 5 - mechanism / opinion, no new human data
Ex vivo animal tissue experiment
PubMed 942392 · doi:10.1042/bj1540709
What was done
Diaphragms isolated from 48-hour-starved rats were incubated in Krebs-Ringer bicarbonate medium at 37°C for 30 minutes, then transferred into new medium and incubated for 1, 2, and 3 hours. Investigators evaluated free amino acid tissue content and release rates following the addition of sodium DL-3-hydroxybutyrate (4 or 6 mM) or sodium acetoacetate (1–3 mM) in the presence of glucose (10 mM) and branched-chain amino acids (0.5 mM), as well as when pyruvate (1.0 mM) replaced glucose.
What was found
Tissue proteolysis prevailed in the isolated diaphragm, primarily releasing alanine and glutamine. Sodium DL-3-hydroxybutyrate decreased tissue content of tyrosine and phenylalanine. In the presence of glucose and branched-chain amino acids, 4 or 6 mM sodium DL-3-hydroxybutyrate caused a 30% decrease in tissue alanine and a 20% decline in alanine release; 6 mM decreased taurine and glutamine release by 19% and 16%, respectively. Sodium acetoacetate (1–3 mM) decreased tissue content of alanine, glutamine, and taurine by 20–35% and decreased alanine and glutamine release by 15–24%, with smaller decreases (<15%) for glycine, threonine, proline, serine, and aspartate. Substituting pyruvate for glucose restored alanine and glutamine release, increased tissue aspartate by 77%, and decreased tissue glutamate by 30%.
Why it matters
This study provides evidence that ketone bodies can directly suppress muscle proteolysis and reduce alanine and glutamine production in starved skeletal muscle, likely mediated by inhibition of glycolysis.
Limits
The experiment is an ex vivo rodent tissue preparation. The abstract reports no sample sizes, variance measures, or statistical significance tests.
Cited by
- supports Ketone bodies are anti-catabolic, reducing the breakdown of skeletal muscle for glucogenic amino acids.