UC Davis

Myoglobin (Mb) is a monomeric protein commonly thought to mediate facilitated diffusion of O2 in muscle tissue and serve as a store for O2. Provocative experiments have revealed reason to doubt this orthodox view of Mb function. In-vivo NMR experiments suggest the diffusion rate of Mb in the cell is too slow to significantly contribute to mitochondrial oxygen flux at physiological pO2, cardiac performance and respiration are not impaired in perfused murine heart in the presence of CO, and the Mb pool in terrestrial mammals can only sustain respiration for a few seconds. Most intriguingly of all, experiments with Mb-knockout (MbKO) mice have measured a shift in metabolic substrate preference from fatty acids (FA) to glucose (Glc), but no deficits in exercise ability compared to wild-type mice. These findings have inspired further research into Mb function. Studies have observed that the lipid oxidation product, 4-hydroxy-2-nonenal (HNE), increases MbO2 auto-oxidation, and several NMR studies have observed binding between Mb and several common fatty acids (FA).

The present study attempts to explore unanswered questions about the significance of these interactions by measuring the effect of HNE and common FA on Mb auto-oxidation and electron transfer (ET) between Mb and cytochrome C (Cyt C). No interactions between HNE and Mb were detected by NMR, and no significant enhancement of Mb auto-oxidation or electron transfer by HNE were measured. By contrast, there was a significant increase in Mb autooxidation in the presence of Oleic Acid, and a significant decrease in electron transfer to Cyt C in the presence of Lauric Acid. Palmitic Acid did not significantly alter either reaction rate. Though unanswered questions remain, Mb’s centrality as a model for the relationship between protein structure and function presents a rationale for further study of Mb – FA interactions.