Question

During a marathon, runners draw heavily on their internal reserves of glycogen and triglycerides to fuel muscle contraction.Initially, energy is derived mostly from carbohydrat3es with increasing amounts of fat being used as the race progresses.  If runners use up their muscle glycogen reserves before they finish the race, they hit what is known as the “the wall,” a point of diminished performance that arises because fatty acids from triglyceride breakdown cannot be delivered to the muscles quickly enough to sustain maximum effort. One trick that marathon runners use to avoid the wall is to drink a cup of strong black coffee an hour or so before the race begins.  Coffee contains caffeine, which is an inhibitor of cyclic AMP phosphodiesterase. How do you suppose inhibition of this enzyme helps them avoid the wall?

Answer 1

Caffeine is identified as a compound which rapidly and reversibly inhibits cAMP-dependent activation of the adenylate cyclase without affecting either cell viability or intracellular levels of ATP or GTP. Studies of the mechanism of action of caffeine show that the drug does not act by inhibiting a cAMP phosphodiesterase, by inhibiting binding of cAMP to its receptor, by itself binding to a physiological adenosine receptor, or by directly inhibiting the adenylate cyclase. Instead, caffeine blocks the cAMP-dependent activation of the adenylate cyclase.

Inside cells, phosphodiesterase normally breaks down the second messenger cyclic adenosine monophosphate (cAMP). Many hormones and neurotransmitters cannot cross the cell membrane, and so they exert their actions indirectly via such second messengers; when they bind to a receptor on the surface of a cell, it initiates a chemical chain reaction called an enzyme cascade that results in the formation of second messenger. The advantage of such a complex system is that an extracellular signal can be greatly amplified in the process, and so have a massive intracellular effect. when caffeine stops the breakdown of cAMP, its effects are prolonged, and the response throughout the body is effectively amplified.

Caffeine enhances fat utilization during exercise, thereby sparing muscle glycogen stores. Caffeine stimulates adipose tissue lipolysis via an increase in catecholamine secretion and consequently promotes free fatty acid oxidation by the active muscle, which, in turn, spares muscle glycogen through substrate competition.