What question did this study set out to answer?

To understand the role of intracellular lactate in myoglobin's interactions with fatty acids under ischemic conditions.

February 21, 2026

BPS2026 – Role of intracellular lactate on muscle tissue’s myoglobin-fatty acid/acylcarnitine interaction in cardiac ischemic conditions

Key Points

To understand the role of intracellular lactate in myoglobin's interactions with fatty acids under ischemic conditions.
Utilized isothermal titration calorimetry to analyze binding interactions.
Employed UV-Vis spectroscopy to observe structural changes in myoglobin.
Conducted oxytherm respirometry to evaluate oxygen kinetics.
Intracellular lactate significantly affects myoglobin's binding and oxygen release capabilities.
Binding affinities of myoglobin for lactate and fatty acids like palmitate and palmitoylcarnitine were quantified.
Lactate facilitates rapid oxygen release from myoglobin when bound to fatty acids.

Abstract

Cardiac ischemia, triggered by coronary artery occlusion, induces a metabolic shift from aerobic to anaerobic respiration, elevating intracellular lactate (LAC) levels and lowering pH, positioning LAC as a critical biomarker. This study investigates molecular interactions between LAC, myoglobin (Mb) (essential for oxygen (O 2 ) storage and transport), and energy metabolism-related metabolites, free fatty acids (FA) and acylcarnitines (AC), which are pivotal for elucidating energy dynamics and cell survival under ischemic conditions. We employed isothermal titration calorimetry (ITC), UV-Vis spectroscopy, and oxytherm respirometry to analyze LAC, FA, and AC interactions with Mb and affect O 2 kinetics. The research aims to determine how these molecular interactions influence Mb’s O 2 release capacity and maintain structural integrity, potentially uncovering novel therapeutic targets for ischemia. ITC experiments demonstrated that oxy-Mb avidly binds to LAC ( Kd = 2.1 ± 0.5 μ M), palmitate PLM ( Kd = 19 ± 1.6 μ M), and palmitoylcarnitine PLC ( Kd = 1.9 ± 0.7 μ M) in one-ligand binding studies, with a 1:1 protein-ligand stoichiometry. Surprisingly, in two-ligand binding assays, no detectable interaction was recorded when second ligand (LAC or PLM or PLC) was added to the pre-bound oxy-Mb. Time resolved UV-vis spectroscopy has shown rapid structural changes to oxy-Mb characterized by a blue shift of Soret peak (435 to 422 nm) with reduced intensity and concomitant conversion of oxy-Mb to met-Mb. These changes occurred in both one- and two-ligand interactions. O 2 kinetic studies have revealed that addition of either PLM or PLC to oxy-Mb did not release O 2 . However, addition of LAC to PLM- or PLC-bound oxy-Mb rapidly releases O 2 . Collectively, these findings suggest that under elevated LAC levels, oxy-Mb undergo auto-oxidation (ferrous, Fe 2+ to ferric, Fe 3+ form), abolishing both O 2 and lipid binding, which might influence the dynamics and effectiveness of fuel transfer to mitochondria.

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BPS2026 – Role of intracellular lactate on muscle tissue’s myoglobin-fatty acid/acylcarnitine interaction in cardiac ischemic conditions

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