Lead-binding proteins - a way to understand lead toxicity?

Abstract

D espite the vast literature on lead toxicity [1], little is known about the biochemical mechanisms responsi-ble for the toxicity of lead and other metals. The gen-eral assumption is that lead interacts with the function of enzymes, signal systems and membranes, probably by bind-ing to certain sites of proteins. Recent studies in the labora-tory in Lund have shown a remarkable specificity for the binding of lead to certain red blood cell proteins, such as δ-aminolevulinic acid dehydratase (ALAD) [2]. This binding causes inhibition of the enzymatic activity. The inhibition of ALAD activity by lead has been known since the 1960s, but there are also other, as yet unidentified, lead-binding pro-teins. By identifying the proteins prone to bind lead, we may be able to understand lead toxicity better; identify enzymatic or other biological processes affected; find markers of lead exposure and effects; identify individuals especially sensitive to the metal; figure out candidates for antidotes; and under-stand how lead is transported within the cell and in the body. The same principle should hold true for other toxic metals as well. Now is a good time to investigate protein-binding of toxic metals. The development of new analytical instrumentation for trace elements and for protein characterization has made it possible to study metals at lower levels than before. Thus, we can now often study the metals in true phy s i o l ogi c a l samples, without the use of radioactive isotopes and without in vitro additions up to concentrations above those physio-logically relevant. At the same time, there has been rapid development in bioinorganic chemistry. Generally, the big leaps forward within the bioinorganic chemistry have been c o n c e rned with the interaction between the essential ele-ments and the biology. As a consequence we now know much about how essential elements usually work in biolog-ical systems. This knowledge lays the ground for learning about the ways toxic elements interfe re with the norm a l functions of the biological systems. This short review paper will deal with lead-binding pro-teins. The aim is not to describe all the details within the field, but to give an exemple of an area where analytical