Adenosine Triphosphate (ATP)

A superstar molecule that you probably know (or do you?)

Adenosine triphosphate, commonly abbreviated to ATP, is probably the biomolecule that you have heard of even if you are not quite sure why. It is arguably the ‘Top Trumps’ of biomolecules, the mover and shaker, the winner in the evolutionary race towards oxidative metabolism. Search engines and other tools of the enthusiastic lexicographer are quick to define ATP (once they have got over all references to tennis) as the energy molecule of the body. Often referred to as the energy currency of the body, its availability for spending being controlled by the Bank of Mitochondrion. All of this is true but it is not the subject of this musing.

What if I was to tell you that ATP has another equally compelling function in the body. A role defined by natural selection and borne out of Nature’s unquenchable spirit of recycling and sustainability. As an essential energy molecule ATP is stored by cells in their cytoplasm, the so-called ATP pools. These stores are continually being replenished by the Bank of Mitochondrion which means that they must also be turned over either as energy currency or ATP is secreted from cells into the surrounding body tissues and specifically into the blood. But ATP is no waste product. The intracellular energy currency is transformed upon its secretion into the blood into the major extracellular signalling molecule of the body. If calcium can be considered the preeminent intracellular signalling molecule then its equivalent in the extracellular environment is ATP. Almost every receptor acting on the surface of every cell everywhere in the body has a complementary receptor for ATP. So, for example, when the major excitatory signalling molecule glutamate acts upon its receptor on the extracellular surface of a neurone, its action is mediated by ATP acting upon an adjacent receptor. You might think about ATP acting in a similar way to a gain control on an amplifier. It moderates the signal generated by the action of glutamate. Multiply this example of glutamate by all other myriad receptors responding to innumerable different signalling molecules and you can very quickly begin to understand how and why ATP is the preeminent extracellular signalling molecule in the body.

Of course, the story cannot end there. Once ATP has acted upon its receptor it must be recycled and this is achieved by enzymes known as ectonucleotidases present in the blood. These enzymes break down ATP in a series of steps and, incredibly, each of the products of the hydrolysis of ATP, namely, adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine are themselves signalling molecules that act upon their own specific receptors. I am probably bamboozling you with too much science and too much detail right now but should you want to know more then check out some of our ground breaking research in this field. As always we stood on the shoulders of a truly great man, Sir Geoffrey Burnstock FRS, in trying to understand this fascinating and fundamental science. How Burnstock did not receive the Nobel Prize for his discovery of ATP as a fundamental signalling molecule throughout biology is beyond my understanding.

But, I can hear you asking, what about aluminium? You know me too well. Why did I spend years researching ATP as a signalling molecule. Why, well when ATP is released from cells into the blood it is rapidly bound by its natural co-factor magnesium to form a MgATP complex. So, when we write about ATP as a signalling molecule we should really be identifying MgATP as the actual signalling moiety. Now, those of you who have read my book and perhaps elsewhere in my substack will already know that aluminium is a major competitor for magnesium and where magnesium binds in biology aluminium binds better. Approximately 1000 times better. We asked the question, what difference might it make if MgATP was replaced by AlATP at an ATP receptor. The answer was intriguing and invariably we found that while AlATP acted successfully at the ATP receptor it was different to MgATP in that it kept the receptor switched on for longer. We first demonstrated this effect in the coronary circulation and we went on to speculate that this effect of AlATP might underlie aluminium’s excitatory toxicity in neurones.

The relatively recent discovery, only in the last fifty years, of ATP as the major extracellular signalling molecule in the body has equally profound implications for the toxicity of aluminium. Aluminium is a known excitoxicant and it may be exerting this latent, perhaps hidden, toxicity throughout the body through its interaction with extracellular ATP. Only future research will confirm or refute this malignant toxicity of aluminium in our everyday lives.