Two biochemical aspects of cell necrosis.

In 1866, Hoppe Seyler was appointed to the Chair of Physiological Chemistry at the University of Tubingen, eight years after Virchow had published his lectures on cellular pathology. Buchner was no more than 6 years old at the time. Biochemistry, as we understand it, did not exist. To-day the dynamic approach which is the essential feature of modern biochemical teaching has produced advances in every biological field into which it has permeated. The technical advances of the last three decades have given a much clearer picture of the anatomy of the giant molecules of which the living cell is built and through which it carries on its normal functions. Moreover, it is now possible to study to what extent and how fast the smaller units of which these giant molecules consist are built into the larger structure. This, if one likes to think of it, is anatomy and physiology at a molecular level. The natural extension of such studies is the examination of disease processes at a molecular level. By that one does not mean the movements of the electrolytes or the accumulations of such small units as urea or glucose, important as these are, but the changes in the character and concentration of the molecular units which comprise the cell itself. This is the logical extension of Virchow's cellular pathology. In the general study of the cell's economy at molecular level one of the most active sections and one that is yielding the most rapid returns is the field of enzymology. Because some of the advances in this field have had direct clinical implications and because they are linked through histochemical studies to formal morbid anatomy it seemed apposite on this occasion to touch on this subsection of biochemistry. Two groups of enzymes, which will be familiar in name at least to all pathologists, have been picked at random for discussion. It is assumed that enzymes circulating in the serum have been elaborated in the cell and that with certain reservations fluctuations in serum levels mirror cellular changes. Indeed, Waterlow (1952) has produced some direct evidence to show that fluctuations in concentrations of circulating pseudocholinesterase parallel their concentrations in liver tissue. However, two points must be borne in mind. It is obvious that one cannot assume that the changes in concentration in the circulation and in the tissue coincide. Moreover, if the apparent fall in circulating enzyme activity is due to an inhibitor incapable of penetrating the "cell membrane" there will be a discrepancy between cell and circulation so long as that inhibitor is effective.