Toxification may result from alterations in enzyme acti¬ 
vity. These alterations may result when excesses of essential 
metals or nonessential metals bind to enzymes. Metalloenzymes 
may be rendered nonfunctional by confirmational changes brought 
about by binding with metals possessing properties different 
from the metals that are required for optimal activity of the 
metalloenzymes. Also, nonfunction may be due to induction of 
conformational changes so that substrate molecules no longer fit 
into binding sites. Alternatively, nonfunction could result 
from splitting of enzymes into subunits, which could interfere 
with feedback control mechanisms. Because any of these reac¬ 
tions could result in impaired metabolic activity, it is not 
unexpected that adverse effects would occur. 
Detoxification mechanisms that have been proposed for metals 
include binding to metallothioneins (MT), which are proteins 
having a high affinity for some metals. This mechanism appears 
to be ubiquitous among organisms; these proteins have been de¬ 
scribed in organisms throughout the animal kingdom (Kagi and 
Nordberg, 1979). They were first characterized in mammals and 
now have been found to have a similar function in fishes, inver¬ 
tebrates, and plants. MT represent a family of inducible, low- 
molecular-weight (LMW), intracellular, cytoplasmic proteins that 
normally bind seven to ten atoms of metals per molecule. These 
proteins have been isolated from kidneys and livers of both 
vertebrates and invertebrates. MT possess a number of unique 
structural and functional characteristics. They contain 2 5 to 
35 percent cysteninyl residues and lack histidinyl and aromatic 
amino acid residues. All cysteinyl-SH groups are involved in 
complexation of metal ions and do not form either intra- or 
intermolecular disulfide bonds. The mode of distribution of 
cysteinyl residues within the amino acid sequence is highly 
conserved among isoforms of the protein from the same organisms, 
as well as those isolated from taxonomically distinct organ¬ 
isms. Recently, considerable information has become available 
on the mode of action and genetic control of MT. 
The induction of the synthesis of MT has been demonstrated 
in aquatic animals exposed to metals. The induction of MT is a 
very significant process, not only because it appears to be im¬ 
portant in detoxification, but also because it can confer in¬ 
creased tolerance to organisms. For some species, this toler¬ 
ance results in increased survival of aquatic organisms and 
their communications; this phenomenon is of significance to 
those managing aquatic resources. 
On the west coast, research on MT in fishes and inverte¬ 
brates has been performed by Dr. Kenneth Jenkins and coworkers 
at California State University at Long Beach (Jenkins et. al. 
1984), Dr. David Brown and coworkers at SCHWRPP (Brown et^ al. 
1984), Dr. Guri Roesijadi and coworkers at Pacific Northwest 
Laboratory at Sequim (Roesijadi et. al. 1982, and by our group 
at Lawrence Livermore National Laboratory (Harrison et al. 1983). 
110 
