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Scientists Pinpoint Where Compound That Helps Metabolism Hangs Out in Muscle Cells

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Researchers from Tokyo Metropolitan University have developed a way of mapping the distribution of carnitine in skeletal muscle cells. Carnitine is a small compound that helps transport fatty acids and reduce metabolic byproducts. They discovered that slow-type muscle fibres contained the most, and that activity promptly led to rises in acetylcarnitine, a product of the immediate response of carnitine contained in the cell. Their technique promises new insights into how muscle cells work. The findings were published in Heliyon.

Our muscles require energy to function. Much of this power is produced in the mitochondria inside cells, where fatty acids are converted into adenosine triphosphate (ATP), the chemical that fuels the vast array of other reactions which help our bodies work. Helping this along is a small compound called carnitine, which helps transport fatty acids into the mitochondria. It is also responsible for lowering the levels of byproducts of the reaction, specifically acetyl CoA (Coenzyme A) which can be toxic in high concentrations. Carnitine binds to acetyl CoA and becomes acetyl-carnitine, ensuring that metabolism in our cells works seamlessly. However, where exactly carnitine resides in muscle fibre cells, and how those levels change over time has remained difficult to study due to the difficulty of labelling it in a way that helps differentiate how much resides where, and how that changes.

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 fibre cells treated with this deuterated carnitine were 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 fibres, fibres responsible for sustained force over longer periods of time than “fast-type” fibres. This is due to the fact that slow-type fibres contain more mitochondria. Furthermore, they applied electrical stimulation to the fibres to simulate muscle contraction before taking the data. They found a significantly elevated uptake of carnitine into the fibres, as well as an elevated level of acetylcarnitine. 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 well-being 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.

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