We call Signals all (physical or chemical) events able to transmit information to a cell. Signaling requires at least two components:
- a physical (e.g. sound) or chemical (e.g. hormone) event that it is released into the environment in specific conditions and that we can call a Sign (S)
- a cellular structure able to react with (S) modifying the cell behavior according to the concentration and direction of (S). These structures are called Receptors ( R ).
Signals structure
Signs are classified as sound, light, hormones, cytokines, chemokines, growth factors, and so on, according to their major effect, but they share a common property: the ability to give information about the existence of specific environments or about the availability of one or more nutrients. The minimal information content carried by any sign is that all the conditions required for its synthesis are present.
Receptors too are synthesized in specific conditions and therefore carry the information that these conditions exist.
- TNF alpha is one sign, but TNF Receptors are more than 20 and each of them elicits a different cellular response.
To make signal understandable to the cell a set of chemical events called signal transduction take place upon binding of the ligand (S) to its receptor.
Non-linearity of signal transduction: ST is a multi-step process with different checkpoints sensitive to different external factors:
- inositol (liver NADH/NAD+, ethanol; oxygen, diet)
- G-proteins (miristoyl and farnesyl availability)
The information content of any Sign includes at least all the factors required for its synthesis
Segni e Segnali
Example1: Thyroid Hormone
Example2: BH4
Every cell is able to synthesize BH4 (tetrahydrobiopterin) from GTP.
BH4 is an essential cofactor for the synthesis of:
- dopamine
- noradrenaline and adrenaline
- serotonine
- NO (Nitric Oxide)
BH4 synthesis is stimulated by Ascorbic Acid (Vit. C)
Why BH4 for NO synthesis?
NO activates Guanylate Cyclase that has as subtrate GTP and produces cGMP. It would be useless to produces NO in the absence of GTP
cGMP blocks L-type Calcium Channel protecting cell from excess stimulation
Why BH4 for excitatory neurotransmitters synthesis?
- negetive feedback on the transmitters release
- local vasodilation
BH4 can be the pace-maker of neuronal activity
Open questions:
- What happens if I treat a hypertensive patient with levodopa?
- What is the correct supply of Vitamin C in elderly?
- Vitamin C for erectile disfunction?
- Why Aldose reductase inhibitors never joined the market?
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