Researchers suggest way of mapping distribution of carnitine in skeletal muscle cells
Tokyo, Japan: Researchers from Tokyo Metropolitan University have devised a method for mapping the distribution of carnitine in skeletal muscle cells. Carnitine is a tiny molecule that aids in the transfer of fatty acids and the reduction of metabolic waste. They discovered that slow-type muscle fibres held the most, and that exercise immediately resulted in increases in acetylcarnitine, a byproduct of the cell's early response to carnitine. Their technique promises new insights into how muscle cells function.
To function, our muscles require energy. Much of this power is generated within cells, in the mitochondria, where fatty acids are converted into adenosine triphosphate (ATP), the chemical that powers the vast array of other reactions that keep our bodies running. A tiny molecule called carnitine aids in the transport of fatty acids into the mitochondria. It is also in charge of decreasing the quantities of chemical byproducts, notably acetyl CoA (Coenzyme A), which can be harmful in large doses.
Carnitine links to acetyl CoA to form acetyl-carnitine, which ensures that metabolism in our cells runs smoothly. However, because of the difficulty of studying carnitine levels in muscle fibre cells, it has remained difficult to determine where they are and how they change over time.
Now, a team of researchers led by Assistant Professor Yasuro Furuichi have come up with a way of studying the distribution of carnitine in muscle fiber cells, and how it changes during metabolic processes. They used a version of carnitine which had some of its hydrogen replaced with deuterium, giving it a distinct signal when studied using mass spectrometry. Mouse muscle fiber cells treated with this deuterated carnitine was rapidly frozen and cut into ultra-thin sections before undergoing a form of imaging where different parts of the section could be separately put through mass spectrometry, giving detailed information as to what kind of compounds reside where.
Firstly, the team discovered that there was a higher concentration of carnitine in "slow-type" muscle fibers, fibers responsible for sustained force over longer periods of time than "fast-type" fibers. This is due to the fact that slow-type fibers contain more mitochondria. Furthermore, they applied electrical stimulation to the fibers to simulate muscle contraction [A1] before taking the data. They found significantly elevated uptake of carnitine into the fibers, as well as an elevated level of acetyl carnitine. Importantly, this shows that carnitine contained in the cells responds very promptly as cells increase their activity.
The team's new method sheds light on a previously inaccessible level of detail regarding the biochemical processes that help muscles function. Carnitine itself is a popular dietary supplement, but its impact on muscular wellbeing is a topic of debate. Quantitative measurement of how it is taken up, localized, and metabolized in cells promises to illuminate the efficacy of therapies.
