Download Metal-Requiring Enzymes (Molecular Biology)

Metal-Requiring Enzymes (Molecular
Biology)
Enzymes that require metal ions for their catalytic activity fall into two classes. They are
the metal-activated enzymes and the metalloenzymes. The latter contain tightly bound metals
that do not dissociate during isolation or dialysis of the enzyme under conditions where
activity is retained. However, such metal ions can be removed under more drastic conditions,
such as low pH. Bound metal ions can be involved with the maintenance of the structural
integrity of enzymes, and they can participate in electrophilic catalysis.
Metal ions that are found in metalloenzymes include those of the first transition series of
elements in the periodic table:
as well as
. Examples of enzymes that contain metal ions
are listed in Table 1. Metal ions involved with enzymes that participate in electron transport
undergo redox reactions. Thus, the ionic forms of iron, copper, cobalt, and molybdenum can
be
respectively.
For convenience, these metal ions will be listed simply as bivalent ions. Fe is most commonly
found as a heme complex in redox enzymes such as catalase and peroxidases (see IronBinding Proteins). It also occurs as a component of iron-sulfur clusters in enzymes that are
involved in one-electron transfer processes; NADH dehydrogenase and succinate
dehydrogenase belong to this group and are flavoprotein enzymes. Like
has multivalent oxidation states, and many Cu enzymes are either
oxidases or hydrolases that utilize molecular oxygen. Co enzymes, such as methylmalonylCoA mutase and ribonucleotide reductase, have the cobalt atom bound within a corrin ring.
Ni is rarely found as a component of metalloenzymes, but urease from jack bean is an
exception. The occurrence of Mn and Ca in metalloenzymes is also somewhat rare (see
Calcium-Binding Proteins). Mg , the alkaline earth metal that is found so commonly in
biological systems, does not play a role in the functioning of metalloenzymes, but is
important in metal- activated enzymes (see below). By contrast, Zn is an important and
widely utilized metal for electrophilic catalysis (see Zinc-Binding Proteins). Not all enzymes
that catalyze a particular reaction have the same requirement for a metal. Thus, fructose
bisphosphate aldolase from yeast and bacteria utilize Zn ions, whereas the same enzyme from
muscle uses a Schiff Base intermediate to activate the substrate (1).
Table 1. Selected Examples of Metalloenzymes
Metal
Ion
Enzyme
amylase, galactosyltransferase, thermolysin
dioldehydrase, glycerol dehydratase, methylmalonyl-CoAmutase,
ribonucleotide reductase
cytochrome c oxidase, dopamine-b-hydroxylase,superoxide dismutase
catalase, NADH dehydrogenase, nitrogenase, peroxidase, succinate
dehydrogenase, xanthine oxidase
arginase, histidine-ammonia lyase, pyruvate carboxylase
nitrogenase, xanthine oxidase
urease, Ni-Fe hydrogenase
alcohol dehydrogenase, carbonic anhydrase, carboxypeptidase,
superoxide dismutase, thermolysin
The largest group of metal-activated enzymes contains the phosphotransferases that
catalyze the transfer of the terminal phosphoryl group of ATP to an acceptor molecule that
can be an alcohol, carboxylic acid, nitrogenous compound, or a phosphorylated compound
(see Kinase). Their essential requirement for a bivalent metal ion is always satisfied by Mg or
Mn . However, other bivalent metal ions have been shown to activate some
phosphotransferases (2). The role of bivalent metal ions in the activation of
phosphotransferases is to form a MgATP complex that then acts as the true substrate for the
reaction. Thus, the binary complex formed by the interaction of the enzyme and its nucleotide
substrate is an enzyme-nucleotide-metal complex. Some phosphotransferases involve a
second metal ion that is liganded by the enzyme as well as the substrate. Examples are
pyruvate kinase and the biotin-containing enzymes that form carboxybiotin by the initial
phosphorylation of bicarbonate to carboxy-phosphate (1). Pyruvate kinase also differs from
most other phosphotransferases in its requirement for K and its inhibition, rather than
activation, by Ca .