5′-Adenosine monophosphate deaminase regulation in ground squirrels during hibernation

Hibernation is an important winter survival strategy for many small mammals. By sinking into a deep torpor where metabolic rate can be as low as 1-5% of the resting rate in euthermia, animals accrue huge energy savings that allow survival, typically without eating, for many months. Hibernating ground squirrels show a net reduction in the total adenylate pool of skeletal muscle during torpor, but the ATP/ADP ratio and adenylate energy charge remain stable. A key enzyme involved in managing adenylate pool size is 5'-adenosine monophosphate deaminase (AMPD). Assessing skeletal muscle AMPD from both Richardson's ground squirrels (Urocitellus richardsonii) (RGS) and 13-lined ground squirrels (Ictidomys tridecemlineatus) (TLGS), the present study shows that muscle AMPD of euthermic versus hibernating animals displays markedly different kinetic properties, differential responses to temperature and to effectors, and is regulated by reversible protein phosphorylation. AMPD activity decreased during hibernation in both TLGS and RGS skeletal muscle, by 70 and 84%, respectively. Stimulation of total protein phosphatases, total serine/threonine protein phosphatases, PP1, PP2B or PP2C, all reduced AMPD activity between 54 and 92% in extracts of euthermic RGS muscle. The same incubation did not change the activity of AMPD from muscle of hibernating animals. Oppositely, both euthermic and hibernating AMPD showed a strong increase in activity when incubated under conditions that promoted the enzyme phosphorylation by PKA, PKC or PKG. Overall, the data indicate that both low activity of AMPD and low affinity of the enzyme for AMP during torpor reduce the rate of adenylate degradation, the primary driver of these changes being covalent phosphorylation of AMPD.

Automated summary

Hibernation is a crucial winter survival strategy for small mammals, allowing them to conserve energy for extended periods without eating. AMPD plays a key role in managing adenylate pool size during torpor, with hibernating animals showing different AMPD activity and properties compared to euthermic animals. The primary driver of these differences seems to be covalent phosphorylation of AMPD.