Structured Water Surrounding Functional Proteins of Muscle and Brain Tissue

It was often the thought that water and its dispersion within cells was a more random occurrence. Yet research in various fields is shedding light of more specific arrangements of water and interactions that occur when it is structured that lend more to its chemical importance. Water is necessary for muscle contraction. Muscle fibers shorten when hydrated (bond water) and lengthen when dehydrated (lose water). This phenomenon is responsible for muscular movement. Szent-Gyorgyi studied muscle protein contraction for much of his career. He observed that muscular contraction is essentially interplay between water and protein, the formation and destruction of water structures induced by specifically built proteins. Muscle is a mechanism that converts changes in hydration into translational motion (Szent-Gyorgyi 1971).

Szent-Gyorgyi and Klotz observed the hydration of muscle fibers and the role of water in the contraction of muscle. Their studies began the early comprehension of the role of water molecules towards substances in tissues. They also developed the ice crystal theory (clathrates and water cages) showing water molecules orienting themselves in crystalline structures about certain ions or specific sites on proteins. Another important realization is that this structuring around substances facilitates not only structural properties but also conduction of electrons in tissues. Observations of the unique features of protein behavior showed that up to five molecules of water could layer between strands of protein forming electron or proton conducting pathways. This correlation in interpretation of protein behavior emphasized the important role played by the solvent in fixing the structure of the solute molecule, as well as, the influence of the solute in imposing a structure on the solvent. It is this mutual interaction which has perhaps not been fully appreciated in the interpretation of the behavior of proteins both experimentally and within biological systems (Klotz 1958, Szent-Gyorgyi 1971, Tait 1971).

Pauling, Klotz and Szent-Gyorgyi, at the time, were looking at the unique structuring of water molecules around various components forming unique lattice structures between or incorporated between biological compounds. Part of Szent-Gyorgyi's work involved the realization and early theory that water played an important role when surrounding a protein in transferring electrons through the water molecule itself via the atoms of hydrogen. Most enzymes and proteins within the cell or surrounding the cell function by the exchange or conduction of electrons through their structures. Certain bio-molecules require oxidation (lose electrons) and others require reduction (gain electrons) in order to continue the dynamic flow of molecular energy conversion. Water molecules were the likely transfer, bridge.

During studies with proteins whereby fixed ratios of water were added to proteins, it was observed that the properties of the proteins, as well as, the properties of water had different characteristics. Reaction kinetics and dielectric constants vary depending on the ratio of water molecules added to a protein suspension. Proteins often have a hydration layer of 5 or so molecules separating the intertwining folds of the protein (secondary structure).

Albumin studies with disulfide bonds (S-S), bonds that occur between sulfur atoms in large proteins that help fold and shape them, showed that reduction occurred for more molecular reducing sites (S-H) than added reducing agent was present. This phenomenon was attributed to the fact that electrons could be transferred by a reduced hydrogen atom (H-) over a water bridge between two atoms of different oxidative states. The most likely theory predicted the transfer of a hydride ion, (H-), between groups of different oxidation states (on the same protein), separated in space but connected by a bridge of oriented water molecules. The concept of H- ion transfer through the lattice of water molecules provides a basis for the interpretation of long range and cooperative energy-transfer processes such as are involved in photosynthesis or in other light activated oxidation- reduction phenomena as well (Klotz et al.1958).

Szent-Gyorgyi and Klotz began to theorize about the transfer of electrons through the water molecules themselves and since water molecules orient between strands of protein molecules this mechanism was another important means for the transfer of electrons, via the transport of H- through the water molecules between them. Since water is polar it has the potential (depending on its environment) to act as a conductor of electrons itself.

Linus Pauling also had theoretical data and devised the clathrate cage theory, now well verified, in observance of how water molecules arranged themselves around substances positioned in biological systems. Water will orient itself around molecules such as an anesthetic drug at particular sites (forming pentagonal dodecahedra) also a temperature dependent phenomenon. He postulated the formation of hydrate microcrystals similar in structure to known hydrate crystals of chloroform, xenon, and other anesthetic agents as these had been observed by x-ray diffraction. He postulated the formation of clathrate water caging of protein ions. This mechanism of having an ion on a protein molecule surrounded by structured water could decrease the energy of electric oscillations in the brain. He theorized that unconscious memory or even hibernation in animals could be a mechanism whereby water in the brain is structured such that consciousness is electrically controlled by water crystal chemistry. When the outside temperature is colder, water arranges in a certain pattern between brain chemicals in such a way that less conductivity occurs and thus parts of brain tissue hibernate, sleep or are unconscious (Pauling 1961). The theory of water being particularly oriented in biological systems in order to enhance or provide a conductive media for electron exchange or further structural and functional properties was a keen interest to Linus Pauling and Szent-Gyorgyi.