Abstract
Histidine containing dipeptides (HCDs) have numerous ergogenic and therapeutic properties, but their primary role in skeletal muscle remains unclear. Potential functions include pH regulation, protection against reactive oxygen/nitrogen species, or Ca2+ regulation. In recognition of the challenge of isolating physiological processes in-vivo, we employed a comparative physiology approach to investigate the primary mechanism of HCD action in skeletal muscle. We selected two avian species (i.e., hummingbirds and chickens), who represented the extremes of the physiological processes in which HCDs are likely to function. Our findings indicate that HCDs are non-essential to the development of highly oxidative and contractile muscle, given their very low content in hummingbird skeletal tissue. In contrast, their abundance in the glycolytic chicken muscle, indicate that they are important in anaerobic bioenergetics as pH regulators. This evidence provides new insights on the HCD role in skeletal muscle, which could inform widespread interventions, from health to elite performance.
Highlights
Remarkable skeletal muscle characteristics, which gives rise to its unique locomotive ability
The phosphofructokinase:lactate dehydrogenase enzyme activity ratio in hummingbirds is far higher than in other vertebrates[19], indicating that the glycolytic conversion of glucose to pyruvate is designed for complete oxidation through the krebs cycle and electron transport chain, and not for conversion of pyruvate to lactate, as occurs when insufficient oxygen is available for complete oxidative metabolism in the mitochondria
Hummingbird m. pectoralis had substantially lower lactate dehydrogenase (LDH) content than either chicken muscle type (p < 0.01 for all between species comparisons), while chicken m. vastus lateralis had more LDH than m. pectoralis (p < 0.01). βm of the chicken m. pectoralis was higher than m. vastus lateralis (p < 0.001), while both chicken samples had a higher βm than the hummingbird m. pectoralis
Summary
Remarkable skeletal muscle characteristics, which gives rise to its unique locomotive ability. If the main role of HCDs in skeletal muscle metabolism is to act either in the primary protection against reactive species or in the regulation of calcium transients and sensitivity, they would be abundantly expressed in the hummingbird flight musculature. In contrast to their outstanding oxidative and contractile properties, hummingbirds have limited capacity for anaerobic metabolism[18,19], most likely because their aerobic capacity renders anaerobic bioenergetics largely unnecessary. Cytochrome C oxidase, subunit IV (COX IV) and lactate dehydrogenase (LDH) content, superoxide dismutase (SOD) activity and in vitro muscle buffering capacity (βm), were measured, and used to provide an indication of the aerobic and anaerobic capacities of the muscle types under investigation, offering further mechanistic insight into the role of HCDs in skeletal muscle metabolism
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