Whether you’re entering the home stretch of a marathon or trying to lug your groceries up that last flight of stairs, you push and push, and just when you think you can’t push any more, your body summons a bit of extra energy to get you through. Where does it come from? An enzyme in our mitochondria that helps tap energy reserves from these cellular powerhouses, according to a new study. Certain dietary supplements could, in theory, help some people access this extra power, but researchers caution the new work doesn’t prove that.
The enzyme in question, carnitine acetyltransferase (CrAT), dwells inside mitochondria. Its job is to convert a key metabolic molecule into a different compound called acetylcarnitine. But CrAT is ambivalent, and it can also orchestrate the opposite reaction, breaking up acetylcarnitine.
To delve deeper into CrAT’s role in energy production, metabolic physiologist Deborah Muoio of Duke University in Durham, North Carolina, and colleagues tested the stamina of two groups of mice by letting them run on a rodent-sized treadmill. One group of animals lacked CrAT in their muscles; the other produced normal amounts of the enzyme. The researchers then forced the mice to work harder by speeding up the treadmill. Whether the treadmill accelerated gradually or abruptly, the mice without muscular CrAT faltered first. They could only run about 70% as far as the control mice before they were exhausted.
Those treadmill results suggest, the researchers conclude, that when muscles run low on gas, they turn to acetylcarnitine to release metabolic raw materials they need for energy-producing reactions. The researchers wanted to determine if boosting acetylcarnitine levels could spur this process and improve the animals’ performance. Muoio and colleagues first tried the experiment on leg muscles removed from the mice and stimulated to contract until their force production fell by half—a way of measuring fatigue. Adding the compound to muscles from the legs of control mice delayed when the tissue began to demonstrate fatigue by 50%. In contrast, acetylcarnitine had no effect on muscles from mice that were missing CrAT.
Then the researchers moved back to working with whole animals, adding one of acetylcarnitine’s chemical relatives to the water provided to the same two groups of mice. After 4 weeks of lapping this mixture, control animals could run 27% farther than they could before the experiment began. But mice that lacked CrAT in their muscles showed no improvement in endurance, the researchers report online today in Cell Metabolism.
Muoio and colleagues also investigated whether the same mechanism operates in people. In a simple procedure that requires only a local anesthetic, they took samples of muscle from athletes who had been training and from ordinary folks of the same ages. They found that the athletes carried more CrAT in their muscle tissue.
The results suggest that acetylcarnitine and CrAT offer an option for tiring muscles, the researchers say. “One way to think about it is that it provides a reserve fuel tank,” Muoio says. “We think it functions when there’s a sudden change in energy demand.”
The study “does contribute to our understanding of the role of this enzyme and the role of acetylcarnitine availability,” says physiologist Mark Hargreaves of the University of Melbourne in Australia, who wasn’t connected to the study. However, molecular biologist Tim Constantin-Teodosiu of the University of Nottingham Medical School in the United Kingdom says years of research show that the study’s authors have the situation backward. Instead of releasing a key metabolic molecule during energy shortages, acetylcarnitine stashes the molecule so that it doesn’t interfere with power-producing reactions. “We don’t believe that acetylcarnitine is a regulator [of muscle metabolism] or that carnitine acetyltransferase is a regulator.”
Acetylcarnitine and the related compound carnitine are widely used dietary supplements. Although researchers have tested both compounds in other experiments with mice and humans, they haven’t established that either improves muscle endurance. “I’m not implying that everyone should be taking carnitine supplements,” Muoio cautions. However, she notes, they could benefit some people whose levels of carnitine or CrAT have declined, such as older folks and individuals who are obese or have diabetes.