The blood lactate/pyruvate equilibrium affair

Abstract

The Lactate Shuttle hypothesis is supported by a variety of techniques including mass spectrometry analytics following infusion of carbon labeled isotopic tracers. However, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover. Here we review the analytical errors, use of inappropriate tissue and animal models, failure to consider L and P pool sizes in modeling results, inappropriate tracer and blood sampling sites, and failure to anticipate roles of heart and lung parenchyma on L:P interactions. With support from magnetic resonance spectroscopy (MRS) and immunocytochemistry we conclude that carbon-labeled lactate tracers can be used to quantitate lactate fluxes.

Mitochondrial Transport in Glycolysis and Gluconeogenesis: Achievements and Perspectives

“…Interestingly, in distinction with that reported by Brooks et al [ 137 ] after 2014 when “The mitochondrial L-lactate dehydrogenase affair” was published [ 22 ], to the best of our knowledge, with the exception of Fulghum et al [ 134 ], there was no denier of the existence of the mitochondrial L-LDH.…”

Tracing the lactate shuttle to the mitochondrial reticulum

“… 2021: Brooks and graduate students review the role of the heart in lactate shuttling 102 . 2021: Brooks and graduate students explain, and review false claims about use of lactate tracers to study metabolism 60 . *Updated from ref.…”

“…The lactate:pyruvate affair Regrettably and inexplicably, thus far, as the use of isotope tracers to study lactate metabolism is concerned, the literature has been muddled, creating a "Lactate:Pyruvate Affair" that needed to be corrected 60 . Specifically, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover.…”

“…Acknowledging that lactate, not pyruvate, is the main gluconeogenic precursor and carbohydrate energy source shared at the organismal and tissue levels upsets archaic concepts of the organization of intermediary metabolism. Nevertheless, despite the evidence, in the manner of Polyphemus, some 58 , 59 have ignored the literature and databases on mLDH and mMCT and their roles in mitochondrial lactate oxidation 60 .…”

“…In the shuttling of carbohydrate carbon energy substrates, lactate concentrations are orders of magnitude greater than those of pyruvate and alanine. Hence, corporal energy substrate distribution is accomplished with lactate, not pyruvate, as the vehicle of mass-energy transfer 60 .…”