Cell Hydrophobicity: A Missed Role For Proteins

Vladimir Matvee

CELL HYDROPHOBICITY: A MISSED ROLE FOR PROTEINS
For a long time, and up to the present, the term hydrophobicity was mostly has been associated chiefly with lipids. The well-known Meyer-Overton rule was always a strong argument in favor of the lipid nature of biomembranes and of the membrane theory of anesthesia. Until the 1960s, to be "hydrophobic" was synonymous with being "lipid", and the hydrophobic properties of the cell were explained by the presence of its lipid membranes, first of all, and primarily the plasma membrane. Indeed, based on these concepts, numerous "lipid" theories of anesthesia were put forward.

However, in the 1960s, when studying thermodynamic characteristics of the thermodynamics of protein folding and unfolding, Brandts (3) was the first to prove convincingly that during the folding of a protein molecule, hydrophobic areas are formed internally which are inaccessible to water. Initially the thermodynamics of conformational transitions in proteins was the subject of study by a small group of specialists. However, with time, it has become evident that hydrophobic areas within cells are represented not only by lipids, as this was thought for more than 70 years, but also by proteins. The importance of this reappraisal is emphasized by the fact that, after water, protein is the most abundant of all other constituents, comprising up to 65% of the dry mass of cells, and greatly exceeds the total amount of lipid. What I propose here is that the volume of the hydrophobic protein phase can greatly exceed that of the hydrophobic lipid phase. However, I also recognize that the full significance of this observation has not been understood and seemingly not accepted by contemporary cell physiologists in terms of paradigms and working hypotheses.

This theme is continued in the article: Vladimir Matveev. Protoreaction of Protoplasm. Cell. Mol. Biol. 51(8): 715-723, 2005.

See full text here:
http://www.actomyosin.spb.ru/protoreaction.htm

Vladimir Matvee

The opposite view on Overton's rule:

Al-Awqati Q.
One hundred years of membrane permeability: does Overton still rule?
Nat Cell Biol. 1999 Dec;1(8):E201-2.

Abstract. The Overton Rule states that entry of any molecule into a cell is governed by its lipid solubility. Overton's studies led to the hypothesis that cell membranes are composed of lipid domains, which mediate transport of lipophilic molecules, and protein 'pores', which transport hydrophilic molecules. Recent studies, however, have shown that hydrophobic molecules are also transported by families of transporter proteins.

Vladimir Matveev's comment: Today it is known 2-3 millions of organic compounds. 200,000 - 500,000 compounds at least are hydrophobic. Does it mean that a cell has a specific carrier for each hydrophobic organic molecule? Maybe tomorrow some new hydrophobic molecules will be synthesized but a specific carrier already waits it to conduct it through membrane into a cell (?). It is interesting story, isn't that so?