Strength & Science Magazine Weekly

AMPK and mTOR: Antagonist ATP Sensors and Control of Protein Synthesis Part II
By: Derek Charlebois B.S. CPT

In part I of this article series, we learned that we can enhance protein synthesis by keeping ATP and phosphocreatine levels elevated and supplementing with free-form leucine. How to accomplish using specific dietary supplements will be discussed in this article.

Keeping ATP and Phosphocreatine Levels High—Creatine Monohydrate + Citrulline Malate

     Creatine is used in the high-energy phosphate or ATP-PCr system to regenerate ATP. ATP, the body's main source of energy, is a molecule of adenosine (adenine + the sugar ribose) linked to three phosphate molecules by high-energy bonds. Breaking of the two outer bonds results in the release of energy.

     When the most outer bond is broken, the energy is released and ADP and Pi are left behind. Creatine, which is bonded to a phosphate ion, transfers energy to the ADP and Pi molecule by breaking its own bond. This regenerates the ATP molecule, which means one now has more energy to use.

     Skeletal muscle has a limited storage of creatine. Therefore supplementing with creatine increases your ability to form ATP and therefore increases the available energy for exercise (Casey et al. 1996 & 2000). More importantly to our topic on hand, by keeping ATP and phosphocreatine levels high by supplementing with creatine we increase protein synthesis through mTOR activation. Creatine also has many other beneficial effects that are to numerous to address here.

Citulline-Malate is the non-essential amino acid citrulline bonded to malic acid, a Kreb’s cycle intermediate. Citrulline-Malate has been shown to accelerate ammonia removal from muscles and delay fatigue. It also increases ATP formation.

Citrulline-Malate has been shown to increase the rate of oxidative ATP production during exercise and the rate of phosphocreatine replenishment post exercise (Bendahan, 2002). At a dosage of 6 grams per day, Citrulline-Malate increased ATP production during exercise by 34% and increased phosphocreatine replenishment post exercise by 20%. Increasing the rate of ATP production during exercise and phosphocreatine replenishment would assist in allowing mTOR to be activated.

Leucine Supplementation

     Leucine is the key regulator of the mTOR-signaling pathway (Anthony et al. 2001 & Lynch et al. 2002). According to Laymen (2003), "The increase in leucine concentration is sensed by an element of the insulin-signaling pathway and triggers a phosphorylation cascade that stimulates the translational initiation factors eIF4 and p70S6K."

     Activation of these initiation factors initiates the translation of muscle mRNA components and are vital for skeletal muscle protein synthesis and creation of new contractile proteins (muscle). Leucine directly signals and primes your muscles to grow through the activation of mTOR.

     Research on leucine shows that once the minimum requirement of leucine for protein synthesis is met leucine can then be used as a precursor for alanine and glutamine or to activate various signaling pathways (Layman, 2003), such as the mTOR pathway. It may sound like leucine is free to exert its powerful effect of mTOR activation, but one must remember that protein breakdown and synthesis is occurring throughout the entire body; the body's protein stores are in a constant state of flux.

     Supplementing with free-form leucine around your workout, a time when leucine oxidation is increased (Shirmomura et al., 2004), ensures that the body’s leucine requirements are met and mTOR can be activated.
Putting It All Together

By supplementing with creatine, citrulline-malate, and free-form leucine one can enhance mTOR activation by increasing ATP production and phosphocreatine replenish as well as direcly activating mTOR via leucine.

Leucine—0.085-.1 gram/lb of bodyweight

Or 0.17 grams BCAA/lb of bodyweight

Creatine Monohydrate—5 grams with breakfast or pre-workout and 5 grams post-workout
Citrulline Malate—3-6 grams a day

Ideally 3 grams taken around your workout

Scivation Xtend—6-10 scoops sipped pre/during/post workout

21-35 grams of BCAA

10.5-17.5 grams of Leucine

3-5 grams of Citrulline Malate

Primaforce Creaform

1 scoop with breakfast
1 scoop post-workout

Derek “The Beast” Charlebois is an ACE certified personal trainer, competitive bodybuilder, and holds a Bachelor’s degree in Exercise Science from The University of Michigan. Derek is the Promotions Coordinator/R&D at Scivation/Primaforce and is involved in coordinating promotions, research and development, advertising, and marketing. Derek is an accomplished author with articles on such websites as Bodybuilding.com, Bulknutrition.com, the online magazines StrengthAndScience.com and MusclesAndCuts.com, and is a contributing author to the book Game Over: The Final Showtime Cut Diet You’ll Ever Need! Derek is available for online personal training. His website is www.beastpersonaltraining.com.

References:
Anthony JC, Anthony TG, Kimball SR, Jefferson LS. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr. 2001 Mar;131(3):856S-860S.
Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJ. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002 Aug;36(4):282-9.
Casey, A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. (1996) Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol. Jul;271:E31-7.
Casey A, Greenhaff PL. (2000).Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance?Am J Clin Nutr. Aug;72(2 Suppl):607S-17S. Review.
Layman, DK (2003). The role of leucine in weight loss diets and glucose homeostasis. J. Nutr. 133: 261S-267S.
Lynch CJ, Patson BJ, Anthony J, Vaval A, Jefferson LS, Vary TC. Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue. Am J Physiol Endocrinol Metab. 2002 Sep;283(3):E503-13.
Shimomura, Y. Murakami, T.Nakai, N. Nagasaki, M. Harri, R.A. (2004). Exercise Promotes BCAA Catabolism: Effects of BCAA Supplementation on Skeletal Muscle during Exercise J. Nutri. 134: 1583S-1587S.