A century of enzyme kinetic analysis, 1913 to 2013.

This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. Finally, several illustrations of modern transient state kinetic methods of analysis are shown which enable the elucidation of reactions occurring at the active sites of enzymes in order to relate structure and function.

The design of an enzyme: a chronology on the controversy.

After the publication of the Monod-Wyman-Changeux model, a controversy arose between Jacques Monod, Francis Crick and Jeffries Wyman about the comparison of the regulatory performances of an oligomer undergoing a concerted transition between two states and a monomer having the same composition and subjected to a similar conformational equilibrium. The controversy took place between September 1965 and March 1966. It gave rise to several unpublished notes. Numerous misunderstandings between the participants were not fully dissipated as the controversy abruptly ended.

Some lessons about models from Michaelis and Menten.

Michaelis and Menten's classic 1913 paper on enzyme kinetics is used to draw some lessons about the relationship between mathematical models and biological reality.

Walter Max Dale (formerly Deutsch) (1894-1969): pioneer and eminent radiobiochemist at the Christie Hospital and Holt Radium Institute, Manchester.

The political upheaval in Germany in 1933 and subsequent movement of medical scholars with the support of the Rockefeller Foundation allowed Manchester to benefit from the arrival of Dr Walter Deutsch, later known as Dr Walter Dale. His research background enabled him to develop a radiobiochemistry laboratory at the Christie Hospital and Holt Radium Institute where he became a world authority on the effects of X-rays on enzymes and also the protective effect of additional solutes. In 1959 he initiated and then edited the International Journal of Radiation Biology. By the time of his retirement in 1962 the strength of his research resulted in his laboratory being recognized by the Medical Research Council.

Enzybiotics: a look to the future, recalling the past.

The discovery and development of antibiotics was one of the greatest successes of Medicine in the 20th century and allowed the control of many diseases caused by microorganisms. Nevertheless, it is necessary to search constantly for new therapeutic tools in the continuing fight against disease-causing microorganisms and this probably leads us to today's concept of enzybiotics. Although microorganism-degrading enzymes have been known since the beginning of the last century, their use was soon forgotten because of the widespread use of antibiotics. The term enzybiotic is a hybrid word from "enzyme" and "antibiotic" and refers to phages: that is, viruses that attack and lyse bacteria and that can potentially help us to fight bacterial diseases. If the concept of enzybiotic is extended to antifungal enzymes, an enormous potential in the struggle against microorganism-due diseases may become available in the foreseeable future.

[Oleksandr Solomonovych Tsyperovych--gifted enzymologist, scientist and practician].

Professor O. S. Tsyperovich (15.12.1910-20.12.1976), Doctor of biology, was born in the city of Odessa, graduated from the Faculty of Chemistry of Shevchenko Kyiv State University as a specialist in organic chemistry (1930-1935). In 1935-1941 he worked at the Institute of Biochemistry of the Academy of Sciences of the Ukr.SSR (Kyiv) as a junior research worker, and then as a senior research worker at the Department of Enzymology. In 1941 O. S. Tsyperovich defended the thesis for the Candidate's degree dedicated to the investigation of synthetic effect of proteolytic enzymes, and he was awarded the title of the senior research worker. In 1941-1945 O. S. Tsyperovich struggled in the ranks of the Soviet Army, was awarded the Red Star Order, medals For Defense of Caucasus, For the Victory over Germany in the Great Patriotic War of 1941-1945. In 1946-1976 O. S. Tsyperovich worked at the Institute of Biochemistry of the Academy of Sciences of Ukraine. When investigating the mechanism of proteins denaturation he discovered the phenomenon of their "denaturational stabilization". New technological schemes of production of pepsin preparations were elaborated on the basis of the method of autholysis proposed by him. In 1954 O. S. Tsyperovich defended the thesis for the Doctor's Degree and was awarded the order The Badge of Honor. Beginning from 1963 he headed the laboratory, and from 1966 -- the Department of Chemistry and Biochemistry of Enzymes, in 1969 the title of professor was conferred on him. In the 60-70's O. S. Tsyperovich investigated hydrolytic enzymes of microorganisms with the purpose of their use in industry. Thus, the method of production of the preparation "pronasa" from Streptomyces griseus was developed, aminopeptidases, dipeptidases, a-amylase, cellulases, were investigated. Investigations in the field of preparative enzymology resulted in the development of technological scheme for creation of the following drugs for the purposes of medicine: medical pepsin, preparation gastric juice, crystalline trypsin, highly purified chemotrypsin, highly purified trypsin, highly purified amylase which were introduced into industry. New methods of silver regeneration from photographic and cinema films with the use of proteinase of S. griseus were developed, as well as the enzyme-antibiotic preparation protezym for hydrolysis of fodder proteins which gave positive results in breeding calves and in feeding adult animals. O. S. Tsyperovich has proposed two simple structures of automatic collector of fractions for the column chromatography, published 178 scientific works including 3 monographs, 10 author's certificates; 12 candidates of science were brought up under his supervision.

Clinical enzymology: an autobiographical history.

In this paper, I review the origins of Clinical Enzymology with special emphasis on the years between 1960 and 1980 when the greatest advances in the subject took place. These are described in relation to my own research interests and contributions, focusing upon subclinical hepatic damage caused by viral infection and by alcohol; myocardial infarction; detection of cervical carcinoma by vaginal fluid analysis; evaluation of pancreatic function; and the clinical implications of microsomal enzyme induction. Reasons are proposed for the failure of enzymology to attain the status of an autonomous medical specialty, in contrast to the success of similar fields of knowledge that grew up in the same era.