Friday, September 24, 2010

The best part of waking UP... is 1,3,7-trimethylxanthine in your CUP.


Caffeine, 1,3,7-trimethylxanthine, (Fig. 1 is the chemical structure of caffeine) is the active ingredient in coffee that stimulates the central nervous system (CNS) impeding drowsiness and restoring alertness. For the athlete, however, it can be used to boost exercise capacity by several mechanisms described below.
Caffeine’s positive affect on exercise capacity comes from its ability to increase the cellular concentration of the molecule cyclic AMP (cAMP). This is achieved by caffeine competitively inhibiting the enzyme that degrades cAMP, the cAMP phosphodiesterase (PDE) (Fig. 2 shows the reaction catalyzed by PDE). PDE converts cAMP into AMP by hydrolyzing the cyclic phosphodiester bond by nucleophilic attack from a zinc coordinated water molecule (Fig. 3 highlights the zinc atom, purple sphere, coordinated to the hydrolyzing water molecule, red sphere, just before nucleophilic attack of the phosphodiester bond). Caffeine is capable of competitively inhibiting PDE because of the structural similarity between caffeine and cAMP’s adenine ring (Fig 4 is the chemical structure of cAMP, compare its adenine ring structure to caffeine’s structure in Fig. 1). The caffeine molecule binds the PDE active site preventing cAMP binding and catalysis (Fig. 3 shows the cAMP molecule in purple with a superpositioned caffeine molecule in magenta highlighting their similar ring structures). Increased cAMP levels activate the protein kinase a (PKA) which subsequently activates specific enzymes involved in lipolysis and glycolysis producing energy from fatty acids and glucose, respectively. These processes increase the capacity to exercise because of the increased energy (ATP) supplied to working muscles.