What are Caffeine and Theophylline?
Caffeine and Theophylline are Methylxanthine compounds.Methylxanthines are organic molecules found in approximately sixty plant species including the Cocoa Tree, Tea Plants, the Kola Tree, Guarana, and especially species of Ilex genus ie: Ilex paraguariensis (the plant from which yerba mate' is made). Methylxanthines are purine alkaloids which means they have a heterocyclic ring with nitrogen included in the ring structure, they are derived from amino acids, are basic in nature, and can generally form water soluable salts. As we all know, caffeine is a mild stimulant, as are all Methylxanthines, but it stimulating properties just scratch the surface of their physiological capabilities.
| Rippening coffee beans | ||
Figure 2 |
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| Fruiting cocoa from which coffee is made. | ||
Figure 3 |
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A flowering Camellia sinensis, the plant
from which tea is made. |
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Figure 4 |
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An X-Ray of a contracted Bronchial tubes. This can be treated using a brochodialator like Theophylline |
Figure 5 |
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| An electron microscope picture contrasting a normal cell (left) to an apoptotic cell (right). |  |
Figure 6 |
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An MRI of the brain which, together with the spinal chord makes up the Central Nervous System. |
| Figure 7 |
Methylxanthine's known physiological affects...
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Methylxanthines are known to have anti-inflamitory properties.
- Theophylline is a bronchodialator. It expands the bronchi by relaxing bronchial muscle. For this reason, as well as the fact that it may have immunomodulatory properites (modifying the body's immune response) it is often used to treat asthma and infant apnea.
- Methylxanthines inhibit the phosphodiesterase enzyme which degrades cAMP, a secondary messenger of nitric oxide. Nitric oxide is a cardiac stimulant.
- Methylxanthines promote wakefulness and increase mental activity. The work as Central Nevous System stimulants.
- Methylxanthines act as diuretics when imbibed with liquids.
- Methylxanthines curb the appetite.
- Methylxanthines reduce the antilipolytic (lypolysis) effect of insulin.
- Methylxanthines increase glucose and free fatty acid concentrations in the blood plasma.
- Methylxanthines are known to act in the induction of apoptosis. High concentrations of Ca2+ and nitric oxide (both are effects of Methylxanthines) are both involved in the stimulation of apoptosis.
Mechanisms of Methylxanthine Compounds:
Methylxanthines have the ability to directly inhibit cAMP Phosphodiesterases, the enzymes which break down cAMP. cAMP Phosphodiesterase does this by hydrolyzing the cAMP and degrading its phosphates. cAMP is a key secondary messenger. It is released, quickly degraded, and then regenerated when it is needed again. When Methylxanthines are present, the phosphodiesterase no longer hydrolyzes the cAMP resulting in an increasing cAMP concentration rather than a decreasing one.
Methylxanthines also have a slowing affect on the reuptake of norepinephrine. Neorepinephrine is a neurotransmitter of the Central Nervous System which uses cAMP as a secondary messanger. By inhibiting the uptake of norepinephrine, the signal to form cAMP remains on for for a longer period of time. This will enhance the already growing concentration of cAMP.
What's more, Methylxanthines are also adenosine receptor antagonists. Adenosine receptors are coupled to regulatory G proteins. When these G proteins are activated they work to deactivate adenylate cyclase, the enzyme which generates cAMP. As adenosine receptor antagonists, Methylxanthines prevent the regulatory G proteins from being activated and as a result, the adenylate cyclase is never deactivated. Once again, intercellular concentration of cAMP are increasing rather than being regulated.
Intercellular cAMP activates PKA (phosphokinase A) a protein which in turn phosphorylates L-type Ca2+ channels. Phosphorylation of L-type channels allows an increases flux of Ca2+ to enter the cytoplasm. Ca2+ is an important secondary messanger and is a mediator of many biochemical pathways including apoptosis.
Figure 8
The cAMP pathway which activates the opening of the L-type calcium channels.
Cambel Berk
cberk@email.arizona.edu
University of Arizona