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Biomedical subjects

R J P Williams

Publications and source records attributed to R J P Williams.

10 recordsLinked to original sources

My past and a future role for inorganic biochemistry.

The first part of this paper describes how my interest in bioinorganic chemistry was stimulated more than sixty years ago and how it has developed. The second part concerns a view of the future of the subject as an essential integral part of systems studies including organisms. After describing the essentials of any irreversible system, explaining how it is inevitably linked to its environment for material and energy, I analyse the roles of inorganic ions in this interactive unity to show the way the accidental oxidation of the environment by organisms has led to an inevitable progression of chemotypes in evolution. What is required in the future is detailed knowledge of the analytical content of the different compartmental structures of organisms, their division between free and bound forms, and the timing of their appearance. Historically this information needs to be related to both environmental and gene changes.

Biochemical Phenomena↗

The discovery of the nature of ferredoxin in photosystems: a recollection.

I describe here my recollection of the story of the discovery of the nature of ferredoxin in photosystems that began in 1965: this story involved the EPR measurements by a young physicist J.H.M. Thornley, using samples provided by J.F. Gibson and D. Hall, and in collaboration with F.R. Whatley.

Electron Spin Resonance Spectroscopy↗

Molecular and thermodynamic bioenergetics.

Studies of biological sciences can be approached in two ways: reductively, as in molecular biology, or holistically, as in systems biology. In this paper, I illustrate my views on approaches to bioenergetics through the analysis of molecular energy transduction and of general thermodynamics relationships in systems biology. The future lies with the second as the first is nearing completion.

Cells↗

Mg and Ca isotope fractionation during CaCO3 biomineralisation.

The natural variation of Mg and Ca stable isotopes of carbonates has been determined in carbonate skeletons of perforate foraminifera and reef coral together with Mg/Ca ratios to assess the influence of biomineralisation processes. The results for coral aragonite suggest its formation, in terms of stable isotope behaviour, approximates to inorganic precipitation from a seawater reservoir. In contrast, results for foraminifera calcite suggest a marked biological control on Mg isotope ratios presumably related to its low Mg content compared with seawater. The bearing of these observations on the use of Mg and Ca isotopes as proxies in paleoceanography is considered.

Animals↗

Metallo-enzyme catalysis.

All organisms depend upon metallo-enzymes. The dependence arises from the inability of individual organic side-chains of proteins to activate molecules such as H2, N2, CH4 and CO and their weakness in hydrolysing many simple compounds such as many peptides, phosphates, even urea. The metal ion sites have been found to be 'designed' for selective uptake and catalytic activity. In this article a few examples will be used to illustrate these points. For more details of all the examples see the reference at the end of this article to Messerschmidt et al. (2001).

Catalysis↗

Evolution was chemically constrained.

The objective of this paper is to present a systems view of the major features of biological evolution based upon changes in internal chemistry and uses of cellular space, both of which it will be stated were dependent on the changing chemical environment. The account concerns the major developments from prokaryotes to eukaryotes, to multi-cellular organisms, to animals with nervous systems and a brain, and finally to human beings and their uses of chemical elements in space outside themselves. It will be stated that the changes were in an inevitable progression, and were not just due to blind chance, so that "random searching" by a coded system to give species had a fixed overall route. The chemical sequence is from a reducing to an ever-increasingly oxidizing environment, while organisms retained reduced chemicals. The process was furthered recently by human beings who have also increased the range of reduced products trapped on Earth in novel forms. All the developments are brought about from the nature of the chemicals which organisms accumulate using the environment and its changes. The relationship to the manner in which particular species (gene sequences) were coincidentally changed, the molecular view of evolution, is left for additional examination. There is a further issue in that the changes of the chemistry of the environment developed largely at equilibrium due to the relatively fast reactions there of the available inorganic chemicals. Inside cells, some of these same chemicals also came to equilibrium within compounds. All such equilibria reduced the variance (degrees of freedom) of the total environmental/biological system and its possible development. However, the more sophisticated organic chemistry, almost totally inside cells until humans evolved, is kinetically controlled and limited by the demands of cellular reduction necessary to produce essential chemicals and by the availability of certain elements and energy. Hence the variability of reductive cellular organic chemistry and its limitations in cells have to be considered separately. While as a whole they drive the oxidation of the environment, they also allow speciation within the major changes of organisms. Human beings have introduced recently new, virtually irreversible, inorganic and organic chemistry in the environment, much of it new modes of irreversible storage of reduced chemicals, and this is, we state, the last possible step of chemical evolution. We must attempt to evaluate its effect on organisms generally. It must be clear that all the changes and the original life forms are dependent upon energy as well as material capture and flow. We shall have to consider in which forms energy was available over the period of evolution, how it was usefully transformed, and the ways in which its sources changed.

Animals↗

The problem of proton transfer in membranes.

Proton (H(+)) transfer has been examined in many molecular systems for more than 50 years. General mechanistic possibilities including tunnelling have been recognized for proton movement from local base-to-base centres. An especially fast mechanism over considerable distances, the Grotthus mechanism, has been described in water. Proton transfer over long distances in membranes which is now known to occur in many protein bio-energetic devices is not understood since ground state structures do not provide a continuous H-bond network. Here we consider the possible mechanisms and propose that the most likely pathway for protons in membranes uses an excited conformational state, equivalent to a partial denaturation.

Animals↗

Overview of the 7th European symposium on calcium-binding proteins in normal and transformed cells.

The strong feature of the meeting was the continuing efforts described in many papers to resolve the multiple ways in which calcium ions are released into cells via messenger signals and then interact with receptors to cause differential internal cellular activation and cell/cell communication. An easy general way to relate these studies to cell components is to start analysis from the genetic structures lying behind all cell activities and then to explore the RNA production, the proteome, the small substrates and calcium levels themselves in turn while referring to the environment of a particular cell, organ or organism. There is then of course the overall physiology. I shall summarize the papers in this order of their main interests.

Animals↗

The involvement of molybdenum in life.

Quite extraordinarily molybdenum is an essential element in life for the uptake of nitrogen from both nitrogen gas and nitrate, yet it is a relatively rare heavy trace element. It also functions in a few extremely important oxygen-atom transfer reactions at low redox potential. This review poses the question "Why does life depend upon molybdenum?" The answer has to be based upon the availability of the element and on chemical superiority in carrying out the essential tasks. We illustrate here the peculiarities of molybdenum chemistry and how they have become part of certain enzymes. The uptake and incorporation of molybdenum are dependent on its availability, selective pumps, and carriers (chaperones), but 4.5 x 10(9) years ago molybdenum was not available when both tungsten and vanadium or even iron were possibly used in its place. While these possibilities are explored, they leave many unanswered questions concerning the selection today of molybdenum.

Animals↗