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"ATP as a Biological Hydrotrope" - high cellular concentrations keep protein from aggregating, etc.

ZeroGravitas

Senior Member
Messages
141
Location
UK
From new research - A secondary, and perhaps very important, function of ATP molecules inside cells appears to be preventing (and reversing) protein aggregation, keeping them and other substances in solution.

Speculation - if pwME/CFS have lower ATP production, and so also lowered concentrations, does this lead to an increase in problems with proteins aggregating inside cells (as happens more often in elderly, e.g. amyloid-beta clumps in neurons with Alzheimer's)? Or are there compensatory mechanisms to compensate, e.g. dumping of proteins and other nutrients from cells? Or is ATP concentration merely preserved inflexibly at the cost of energy use?

Research paper Abstract published in Science: http://science.sciencemag.org/content/356/6339/753.long
ATP boosts protein solubility
Adenosine triphosphate (ATP) has well-characterized roles in providing energy for biochemical reactions within cells. Patel et al. find that ATP may also enhance protein solubility, which could help explain why such high concentrations of ATP are maintained in cells (see the Perspective by Rice and Rosen). Protein concentrations in cells can exceed 100 mg/ml. The authors found that ATP at concentrations found in cells could act as a hydrotrope to help solubilize hydrophobic proteins. The results raise the possibility that ATP concentrations could influence processes such as protein aggregation that occur in disease or liquid-liquid phase separations that occur within cells.

Science, this issue p. 753; see also p. 701

Abstract
Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical surfactants in that they have low cooperativity of aggregation and work at molar concentrations. Here, we show that adenosine triphosphate (ATP) has properties of a biological hydrotrope. It can both prevent the formation of and dissolve previously formed protein aggregates. This chemical property is manifested at physiological concentrations between 5 and 10 millimolar. Therefore, in addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells

Via article on The Longevity Reporter (below): http://longevityreporter.org/blog/2017/6/8/why-do-our-cells-contain-so-much-atp
ATP is the universal energy currency in living organisms. So, the question why our cells contain so much of it may seem strange. Yet, ATP concentrations in the cell are about a thousand fold higher than the concentration typically required for enzymes to do their job. One explanation is that the high concentrations are needed to fuel the multitude of reactions taking place simultaneously within the cell. But now a new paper published in Science suggests that there’s another reason why our cells contain so high ATP concentrations, ATP helps to keep the proteins in our cell soluble.
Everyone has experienced that salt or sugar has a limited solubility in water. No matter how much you stir or shake at a certain point no more salt or sugar will dissolve. Just like salt or sugar other molecules also have a limited solubility in water. Our cells contain an incredibly concentrated solution of proteins, metabolites, nucleic acids, and other molecules. Failure of molecules to stay soluble results in diseases. For example, in amyloid-beta proteins start to clump together in Alzheimer’s disease, losing their solubility and eventually forming insoluble protein clumps known as plaques.
In this new paper, researchers demonstrate that ATP helps to keep proteins soluble by acting as a hydrotrope. First described in 1916 by the German biochemist Carl Neuberg, hydrotropes are molecules that greatly increase the solubility of otherwise badly soluble organic molecules in water. For example, many liquid detergents, liquid soaps, and shampoos contain hydrotropes to help keep the detergent molecules dissolved.
The authors speculate that the age-related decrease in cellular ATP could contribute to a loss of protein solubility and hence explain the increased incidence of neurodegenerative diseases, like Alzheimer’s disease, with age.