Ergogenic compounds improve physical performance in many different ways. They may enhance physiological capacity, augment the recovery rate from training and competition, or remove psychological barriers. Thus far the biochemical underpinnings of many ergogenic aids are tremendously misunderstood. This creates an environment where many ergogenic compounds possess unproven qualities potentially leading to misuse.
Creatine is somewhat of an exception to that rule. It has been heavily examined by research scientists yet some of its functional details are still unclear. What is known about creatine is that after human consumption during times of energy surplus, creatine will be converted to creatine phosphate (Fig. 1 is the chemical structure of creatine phosphate) by the enzyme creatine kinase. Creatine phosphate functions by donating its phosphate group to ADP replenishing ATP concentration and extending the possible duration of muscular contraction (Fig. 2 illustrates the ATP regeneration cycle utilizing the phosphate group from creatine phosphate [CP]). For that reason, athletes consume a copious amount of creatine, which is converted to creatine phosphate and enhances muscular contraction and strength.
In addition to creatine phosphate’s well established impact as a phosphate donor, creatine may confer additional ergogenic effects during energy-depleted periods by putatively modulating the energy-sensing AMP-activated protein kinase (AMPK)(see post from 9-6-10). Creatine, signifying low energy, might activate AMPK. Creatine activation of AMPK would enhance physical performance by encouraging cellular influx of glucose increasing ATP production which facilitates muscle contraction and hypertrophy.
The molecular features of creatine/creatine phosphate’s interaction with AMPK are unknown. Interestingly, our AMPK crystal structure reveals a large positively charged surface near the ligand binding sight (Fig. 3 shows the AMPK electrostatic surface potential with blue and red representing electropositive [+4 kbT] and electronegative [- 4 kbT] regions, respectively. The putative creatine phosphate binding site is highlighted by a red asterisk)., suggesting a possible interaction with the negatively charged creatine phosphate and a possible mode of regulation similar to ATP.
In conclusion, greater molecular insight into creatine's function during high and low energy conditions will maximize benefit by revealing the most efficacious prescription for creatine consumption. For instance, given that creatine purportedly functions during high and low energy states, perhaps creatine consumption should occur before, during, and immediately after exercise.
