The anabolic effect of leucine

Protein synthesis is a term you will come across frequently when reading articles about building muscle. But what exactly is protein synthesis? Put simply, the term protein synthesis describes the build-up of new body proteins, which includes muscle protein.

When this build-up of muscle protein occurs on a larger scale, it is also referred to as hypertrophy or muscle growth and this is the process by which our muscles become larger. This article looks at how the amino acid leucine regulates skeletal muscle protein synthesis after training.

What role does training play?

Different forms of training influence muscle protein turnover in different ways. Endurance training affects muscle protein turnover by reducing the rate of skeletal muscle protein synthesis and increasing the rate of protein or muscle breakdown.

Training with weights, also known as resistance training, is unique compared to other forms of training in terms of its effect on muscle protein turnover, as a training session with weights increases both the rate of skeletal muscle protein synthesis and the rate of skeletal muscle protein breakdown. The overall effect of both endurance training and resistance training is a negative net protein balance or muscle breakdown.

In the short term, training therefore results in a catabolic state in both cases. In the long term, however, resistance training is associated with maintaining or increasing muscle mass.

The role of leucine

It has been shown that for a positive protein balance after training, protein and in particular the amino acid L-leucine must be consumed and that the protein balance will remain negative until protein and leucine are consumed.

Leucine is one of the three branched-chain amino acids, also known as BCAAs. Leucine is unique in its ability to stimulate skeletal muscle protein synthesis. In fact, leucine has a factor of 10 greater effect on protein synthesis than any other amino acid.

But how exactly does leucine stimulate skeletal muscle protein synthesis? To understand this, we first need to understand the pathway that leucine activates. It has been shown that leucine activates one of the most important complexes of the anabolic pathway, known as the Mammalian Target of Rapamycin (mTOR).

mTor is a protein synthesis regulator, an energy sensor and a nutrient sensor for the availability of amino acids - in particular the amino acid leucine. mTor is activated when ATP levels are high and is blocked when ATP levels fall. The activation of mTOR is crucial for skeletal muscle hypertrophy.

You can think of mTOR as the cell's amino acid sensor, which reacts sensitively to higher leucine concentrations. Decreasing leucine concentrations signal mTOR that there is not enough dietary protein to synthesize new skeletal muscle protein, which results in mTOR being deactivated. When leucine concentrations increase, this signals mTOR that there is sufficient dietary protein to synthesize skeletal muscle protein and mTOR is activated.

The activation of mTOR

Although scientists do not yet know exactly how leucine activates mTOR, it has been shown that mTOR is sensitive to leucine concentration and ATP levels. Falling ATP levels, just like low leucine concentrations, can reduce the activation of mTOR. Activation of mTOR is closely associated with an increase in the rate of protein synthesis. mTor increases the rate of protein synthesis via two different mechanisms:

Mechanism number 1

mTOR phosphorylates a binding protein called 4E-BP1 and deactivates it. When 4E-BP1 is activated, it binds a protein called eIF4E and prevents it from combining with another protein called eIF4G to form the eIF4E*eIF4G complex. The formation of this complex is a critical factor for the continuation of protein synthesis

In short, by deactivating 4E-BP1, mTOR ensures that the eIF4E*eIF4G complex can be formed, thereby allowing protein synthesis to continue.

Mechanism number 2

mTOR activates a protein called ribosomal protein S6 (aka rpS6 or p70 S6). rpS6 increases the synthesis of components of the protein synthesis pathway. mTOR therefore not only increases the rate of protein synthesis, but also increases the capacity for protein synthesis.

An analogy that can help to better understand this mechanism would be to compare it to a construction company building a new skyscraper. The construction company would be mTOR and the skyscraper would be the protein you are trying to synthesize. The construction equipment needed to build the skyscraper would be the components of the protein synthesis pathway and leucine would be the money needed to fund the project.

If enough money is available (increasing leucine concentrations), then the construction company can not only start building the skyscraper (synthesizing muscle protein), but also buy more machines (increasing the amount of protein synthesis pathway components) to increase the capacity and speed at which the skyscraper is built (the muscle protein that is synthesized).

Leucine also increases the rate of protein synthesis by increasing the availability of eIF4G for the formation of the eIF4E*eIF4G complex by increasing the phosphorylation of eIF4G.

The effects of leucine supplementation in practice

Now that we have the dry science behind us, the question is what it tells us. Is there a benefit to supplementing extra leucine, or is a high protein diet enough to provide sufficient leucine? There is some evidence that supplemented leucine may have benefits even with adequate protein intake.

Recently, scientists conducted an experiment in which subjects performed 45 minutes of resistance training and then supplemented with carbohydrates, carbohydrates & 30 grams of protein, or carbohydrates & protein & leucine.

The scientists found that the carbohydrate/protein/leucine supplement reduced protein breakdown more and increased skeletal muscle protein synthesis more than the carbohydrate/protein supplement and the carbohydrate-only supplement.

One possible explanation for these results could be the rapid increase in plasma leucine levels that can be achieved with the help of the leucine supplement. Complete proteins linger longer in the stomach and intestines before the amino acids they contain enter the bloodstream. As a result, leucine plasma levels rise more slowly and reach a plateau.

Even with fast-digesting proteins such as whey protein, it can take hours for the leucine contained in the protein to be released and enter the bloodstream. For this reason, leucine plasma levels will never reach high peaks.

An isolated leucine supplement, on the other hand, is rapidly absorbed and enters the bloodstream quickly, resulting in a sharp increase in plasma leucine levels and a dramatic increase in intracellular leucine concentrations, activating the anabolic pathways described above.

Conclusion

After reading this article, it should be clear to everyone that leucine increases protein synthesis by increasing the activity of mTOR and the phosphorylation of eIF4G.

Leucine has a far greater stimulatory effect on protein synthesis than any other amino acid and it has been shown that protein synthesis responds to a relatively small amount of leucine in a similar way to a full protein meal.

It has also been shown that the addition of leucine to a high protein meal further increases the rate of skeletal muscle protein synthesis.

However, further research is needed to show whether athletes can benefit in the long term from supplementation with leucine in addition to a high-protein meal in terms of an additional increase in muscle mass.