Effect of fatty acid interaction on myoglobin oxygen affinity and triglyceride metabolism
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ORIGINAL ARTICLE
Effect of fatty acid interaction on myoglobin oxygen affinity and triglyceride metabolism Thomas Jue 1 & Gregory Simond 1 & Traver J. Wright 2 & Lifan Shih 1 & Youngran Chung 1 & Renuka Sriram 1 & Ulrike Kreutzer 1 & Randall W. Davis 2
Received: 9 November 2016 / Accepted: 8 March 2017 # University of Navarra 2017
Abstract Recent studies have suggested myoglobin (Mb) may have other cellular functions in addition to storing and transporting O2. Indeed, NMR experiments have shown that the saturated fatty acid (FA) palmitate (PA) can interact with myoglobin (Mb) in its ligated state (MbCO and MbCN) but does not interact with Mb in its deoxygenated state. The observation has led to the hypothesis that Mb can also serve as a fatty acid transporter. The present study further investigates fatty acid interaction with the physiological states of Mb using the more soluble but unsaturated fatty acid, oleic acid (OA). OA binds to MbCO but does not bind to deoxy Mb. OA binding to Mb, however, does not alter its O 2 affinity. Without any Mb, muscle has a significantly lower level of triglyceride (TG). In Mb knock-out (MbKO) mice, both heart and skeletal muscles have lower level of TG relative to the control mice. Training further decreases the relative TG in the MbKO skeletal muscle. Nevertheless, the absence of Mb and lower TG level in muscle does not impair the MbKO mouse performance as evidenced by voluntary wheel running measurements. The results support the hypothesis of a complex physiological role for Mb, especially with respect to fatty acid metabolism.
Keywords Lipid . Fatty acid . NMR . Metabolism . Bioenergetics
* Thomas Jue [email protected]
1
Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA 95616-8635, USA
2
Department of Wildlife and Fisheries Sciences, Texas A&M University, College Station, TX 77843, USA
Abbreviations OA oleic acid PA palmitic acid TG triglyceride KO knock-out FABP fatty acid binding protein Mb myoglobin MbCO carbonmonoxy myoglobin
Introduction Conventional physiology usually asserts an O2 storage and a facilitated O2 transport role for Mb, even though many questions still abound about its cellular function [7, 23, 39, 53, 54]. The total O2 store of Mb in mammalian heart can only sustain normal respiration for seconds [6]. CO inactivation of Mb function does not impair cardiac respiration, metabolism, or contraction [8, 16]. A mouse without Mb, a myoglobin knockout (MbKO) mouse, exhibits no deficits in its oxygen consumption rate, contractile function, and bioenergetics [15, 20]. Moreover, several studies have now shown that Mb in situ or in a muscle fiber model appears to diffuse too slowly to compete effectively with free O2 under normoxic conditions [32, 33, 37, 38]. Nevertheless, researchers continue to interpret the switch toward glycolysis in MbKO myocardium as evidence supporting a singular Mb role in facilitated O2 transport. Other researchers have proposed an alternative explanation for the switch toward glycolysis in
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