A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution
Introduction
The cell membrane lipid bilayer is the home of about one third of all known cellular proteins. These are the transporters, ion channels, receptors and signalling systems, and are dependent on the lipid domains in which they sit. The species, organ and even sub-cellular specificity of lipids testifies to exact demands of differentiated cells and precise protein–lipid interactions. For example, the membrane lipid composition is different for the endothelium, heart muscle, kidneys, liver and brain. Even within a given tissue, there are specific differences in the plasma membrane compared to the mitochondria and nuclear envelope.
The highly specific, characteristic differences in the plasma membranes of the neural, endothelial and epithelial cells; or glomerulus and distal tubules of the kidneys, cannot be based on vague compositional directives. We propose this constancy and specificity is a function of specific protein–lipid interactions operating in a multi-dimensional fashion similar to what has been described for proteins. This relationship has to be a two way system. During cell differentiation, the specialist proteins that arrive will seek a lipid match and vice versa [1], [2]. If the matching lipids are not present the system may fail, regardless of the protein components.
Proteins are built with 20 amino acids that are assembled into three-dimensional structures. Because of the molecular motion of the final protein assembly, it is an example of supra-molecular chemistry which includes reversible non-covalent associations, hydrogen bonding, metal coordination, π–π interactions and electrochemical effects involving lipophilic and hydrophilic structures. In that sense a protein in a living cell exists in six dimensions.
4th Dimension: electrochemical profile.
5th Dimension: van der Waals type forces.
6th Dimension: time. The time of occupancy of the state which optimises the probability of electron cohesion.
The van der Waals equation can be written as follows:where p is the pressure of the fluid, T is the absolute temperature, a′ is a measure for the attraction between the particles and b′ is the average volume excluded from v by a particle. This equation can be utilised to describe lipid properties: a′ will vary with the chain length and degree of unsaturation. Chain length and saturation affect the pK of the acid, which in turn is a determinant of the lipid polarity. b′ will also vary with physical chain length of the fatty acid (16–24 carbons) and degree of unsaturation (1–6 double bonds), as well as with lipid concentration—especially since lipids form micelles and other macromolecular structures in aqueous milieus. The degree of unsaturation is also responsive to T and p.
Therefore lipids are not just an oil phase separating two aqueous regions as is frequently depicted, but have physical, chemical and electromagnetic properties which are operating in cellular functions in multiple dimensions. The electrical properties of the phospholipid head group and ceramides (and possibly the entire lipid chain) can be considered to exist with the same principles as described for proteins, but with a stronger temperature and pressure variation and a larger number of possible constituents. The idea that lipids interact specifically with membrane proteins is not new [1], [2], [3].
Section snippets
DHA abundance controls brain size and function
Comparative evidence on brain composition gave us the first clue to consider both proteins and lipids in six dimensions, and that lipids may specify proteins just as proteins specify lipids. In some animals DHA (-cis-docosa-4,7,10,13,16,19-hexaenoic acid or C22:6n-3) is present either in the diet or as a product of the strongly rate limited synthesis from plant-derived α-linolenic acid (C18:3n-3) [4]. If the velocity of body growth is small then adequate synthesis of DHA for brain growth can
DHA and the origin of vision and the brain
For the first 2.5 billion years of evolution, there was little change in prokaryote life forms, dominated by anaerobic algae and bacteria. Amino acids have been recovered from carbonaceous chondrite meteorites, which are nearly as old as the Solar System (4.6 billion years), so we can assume these life forms utilised proteins. However the synthesis of DHA requires 6 oxygen atoms for the introduction of the 6 double bonds; therefore it is unlikely that there was an abundance of DHA before
Energy minimised structures and quantum communication
The van der Waals equation hints that DHA will have both stereochemical and electromagnetic properties. Quantum mechanics can predict the existence of energy levels inside lattices, whereby any electron in that level can be effectively spread across the whole structure, thus becoming a quasi-particle or a wave. Albert Szent-Gyorgyi postulated that common energy levels could exist in protein structures, as they contained “a great number of atoms, closely packed with great regularity”. He
Electron coherence in DHA
Crawford et al. [28] proposed a possible mechanism whereby photoreceptor membranes could be responsible for the electrical current seen in this system by Jin et al. [29]. DHA is present in greater than 50% of the outer rod segment membrane phosphoglycerides, with some phosphoglycerides containing two DHA molecules. Crawford et al. [28] postulated that the π-electrons of the double bonds are confined to potential wells by the intervening methyl groups. Confinement can lead to stationary states:
The Kronig Penney model
To test this idea further we have examined Kronig Penney Model.2 The long range transfer of electrons inside proteins is reliant on the tunnelling effect [24], [35]. One of the issues that makes tunnelling so hard to predict and\or observe directly is that the nuclear configuration changes constantly, as do the electronic configurations of the donor and acceptor states. Nonetheless, at times of resonance, electrons localised on the donor site will tunnel
Nuclear overhouser enhancement
To test the electromagnetic properties of π-electrons and the –CH2– groups in DHA we studied its behaviour in a magnetic field. We used the Nuclear Overhouser Enhancement (NOE) technique whereby the molecule is exposed to an NMR magnetic field. The magnetic field is then switched to the opposite polarisation [40], [41]. If there is no response the spectra are identical at both polarities. If there is a response, the subtracted spectra record the electromagnetic activity in specific region(s) of
Conclusion
As far as our knowledge goes, DHA has been the dominant fatty acid in the membrane phosphoglycerides of the photoreceptors, neurones and synapses for all 600 million years of animal evolution. Even today, the composition of the photoreceptor and brain varies little between species despite large scale species variation in the lipid composition of the diet, liver and muscle. This consistency is despite the fact that its DPA precursor, which differs by only two protons, is more readily available,
Acknowledgements
We wish to thank the Letten and Mother and Child Foundations for their support. We are also grateful to the Uganda Game Department, Makerere Medical College and the Zoological Society of London for their contribution to the initial evidence for the significance of DHA in the evolution of the brain. This paper is in recognition and memory of the late Philip Tobias whose support following his Dual Congress of Paleoanthropology and Biology, in Sun City, South Africa 1998 was an important stimulus
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