title: D-Lactate altered mitochondrial energy production in rat brain and heart but not liver.
abstract: BACKGROUND
  Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart.
  
  
  METHODS
  Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination.
  
  
  RESULTS
  In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates.
  
  
  CONCLUSIONS
  DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada. Gordon.Zello@usask.ca.
authors.forename: Binbing
authors.initials: B
authors.lastname: Ling
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Jane
authors.initials: J
authors.lastname: Alcorn
authors.forename: Katharina
authors.initials: K
authors.lastname: Lohmann
authors.forename: Brian
authors.initials: B
authors.lastname: Bandy
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Zello