The Caffeine Decoy

Swallowed, then absorbed into the blood

Caffeine travels down the esophagus to the stomach. A little is absorbed there, but most passes into the blood through the wall of the small intestine.

That blood goes to the liver first, then to the heart and lungs. The heart then pumps it out to every organ, including the brain.

of the caffeine gets absorbed

≈ 99%

for almost all of it to be absorbed

≈ 45 min

Small enough to slip into the brain

The brain's blood vessels are lined with tightly sealed cells. This wall, called the blood-brain barrier, keeps most things in the blood out of the brain.

Caffeine is a small molecule that dissolves in both water and fat, so it passes straight through. Brain levels quickly match blood levels.

molecular weight (a sugar molecule is 180)

194

crosses the blood-brain barrier

Freely

Adenosine, the brain's tiredness signal

1. Brain cells (neurons) send signals all day long.
2. They run on a fuel molecule called ATP.
3. Every signal burns some of that fuel.
4. What's left over is adenosine, which leaks out of the cell.
5. It piles up the longer you're awake. The more there is, the sleepier you feel. Sleep clears it away overnight.

Adenosine presses the brakes

Neurons have adenosine receptors on their surface. When adenosine fits into one, the receptor switches on and tells the neuron to slow down.

The neuron fires less often and releases fewer of the chemicals that keep you alert. You start to feel drowsy.

the two receptor types caffeine blocks

A1 · A2A

times each receptor weaves through the cell's outer layer

7

A near-perfect lookalike

Side by side, the trick is clear. Both molecules are built on the same double-ring core. Caffeine is shaped enough like adenosine to fit into the same receptor.

But caffeine has no sugar ring, and adenosine needs that sugar to switch the receptor on. So caffeine fits the lock without turning it.

double-ring core both share (a purine)

Same

what caffeine is here (an "antagonist")

Blocker

Blocked, so the brakes come off

Adenosine doesn't stay stuck. It binds and lets go over and over. Each time a receptor comes free, caffeine can take the spot. A receptor holding caffeine stays switched off, and adenosine can't get in.

With fewer brake signals, neurons stay more active and release more alertness chemicals like dopamine and glutamate. You feel more awake.

Caffeine hides tiredness. It doesn't remove it. The adenosine is still there, and when the caffeine wears off it can bind again. That's one reason people feel a crash.

The liver breaks it down

An enzyme in the liver called CYP1A2 does about 95% of the work. It turns caffeine into three related compounds, which later leave the body in urine:

• Paraxanthine≈ 84%
• Theobromine≈ 12%
• Theophylline≈ 4%

In most healthy adults, half the caffeine is gone after about 5 hours (usually 3 to 7). Smoking speeds this up. Pregnancy and some medicines slow it down a lot.