Metabolism of Caffeine

Caffeine is absorbed in the small intestine, metabolized in the liver cell and distributed to body tissues within 45 minutes of ingestion.

It has a half-life of 3-5 hours in adults but can have a half-life of up to 80 hours in pregnant women prior to delivery.

Caffeine breaks down into the following components:

Caffeine Metabolites

Paraxantine has the effect of increasing lipolysis (break down of lipids), leading to elevated glycerol and free fatty acid levels in the blood plasma. Theobromine dilates blood vessels and increases urine volume. Theophylline relaxes smooth muscles in the brochi, however, the amount that it forms from caffeine is insignificant to produce pronounced results.

The overall mechanism and enzymes that caffeine interacts in order to be broken down are following:

Caffeine Pathway

Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic AMP. This increase of cyclic AMP usually mediates most of the pharmacological actions of caffeine. This is due to caffeine’s structural similarity with adenosine.

By blocking the degradation process of cyclic AMP, caffeine indirectly affects regulation of cAMP-dependent protein kinases, which are responsible for the regulation of glycogen, sugars and lipid metabolism. In addition, it stimulates the release of hormones, in particular: epinephrine (adrenaline).

Caffeine stimulates all levels of the CNS, although its cortical effects are milder and of shorter duration than those of amphetamines. In larger doses, caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3',5'-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. More recent studies indicate that caffeine exerts its physiological effects in large part through antagonism of central adenosine receptors.

Structures of Caffeine and Adenosine