The Metallobiochemistry of Zinc Enzymes

Abstract

The honour and opportunity of being invited to address you on the occasion of Professor Houtman's retirement is very much appreciated. However, having met him yesterday, I am convinced that I am not here to help celebrate his retirement as much as to initiate his new career.Just like careers, the role of metals in biology can be viewed from multiple points of view. In the past, metals have variously been thought to be beneficial, toxic or to serve no purpose at all in biology. It is not very long ago that documentation for the validity of all th ree perceptions seemed to coexist, and that they had equally vigorous advocates; but by now the hypothesis that they serve no biological purpose has faded into oblivion. This dilemma owed much to the fact that many metals are present in 'trace' amounts. I want to address myself today to the general principles underlying the evolution of metallobiochemistry and of its subdisciplines which did not exist a generation ago and give perspective to metals as toxic, environmental agents, a subject which has been of special interest to Prof. Houtman.The word 'trace' implies something that can be measured qualitatively but not quantitatively, and until about a generation ago that was true for many metals in biology. Therefore it was a nearly mystical subject explored of ten by individuals who had ideas about the problem but who performed few experiments to verify or reject them. This has changed. Measurement of very low concentrations of metals in biology has become quite routine. Technical problems have been eliminated to the point where the term 'trace' has become meaningless. That is fortunate, indeed, because to many 'trace' also meant 'unimportant' or 'insignificant' .Attention to the detection limits of analytical methods for metals has become almost irrelevant now. Yet, the fact that the II-B metals and those of the first transition series all occur in biological matter in similarly low concentrations led to the tacit inference that all of them would be found to perform similar functions. Such an emphasis on similarities of concentrations completely ignored the chemical properties of metals which are unique for each. Not too surprisingly, their biological roles have turned out to be as characteristic as their chemistries, enhanced by co-ordination of metals with 132 12 (1988) DELFT PROGRESS REPORT

Zinc

“…The majority of enzymes in the latter category bind zinc only loosely, and are activated by the addition of a variety of metal ions (Vallee and Wacker 1970). According to Vallee and Galdes (1984), zinc enzymes are involved in the replication, transcription, and translation of genetic material of all species. The specific role of zinc in gene transcription has been characterized by Wu and Wu (1987).…”

The Metallothionein/Thionein System: An Oxidoreductive Metabolic Zinc Link

“…[3] The study of this and other zinc enzymes such as carboxypeptidases A and B, alcohol dehydrogenases, alkaline phosphatases, and thermolysin, formed the basis of zinc metalloenzymology. [11] The functions of zinc in enzymes were then designated as catalytic, coactive (or cocatalytic) and structural. [3] These realizations were pivotal.…”

Some effects of zinc on maternal and fetal intergrety in pregnancy

“…Zinc is an essential trace element and plays important roles as a component of many co-factors and enzymes involved in protein synthesis (Vallee and Goldes, 1984). Clearly, there exists in all cells an optimal zinc requirement for growth and function.…”