Zinc enzymes lyases

This review will give a subjective account of mechanistic studies on some representative zinc enzymes comprising the enzyme classes I-IV (oxidoreductases, transferases, hydrolases and lyases). It does not claim to be comprehensive, as a comprehensive review would be far too extensive for this work. Lowther and Matthews have reviewed the met-alloaminopeptidases and Noodleman and coworkers have reviewed calculational studies on metalloenzymes. We apologize in advance for any omissions and point to previous reviews on this and related subjects to be found, e.g., in References 7-11. 

We have already seen the diversity of function in the lyases, hydrolases and oxidoreductases. Several other types of zinc coordination are found in a number of other enzymes, illustrated in Figure 12.8. These include enzymes with the coordination motif [(His)2(Cys) Zn2+-OH2], illustrated by the lysozyme of bacteriophage T7 this group also includes a peptidyl deformylase. 

Zinc is an essential trace element. More than 300 enzymes that require zinc ions for activity are known. Most catalyze hydrolysis reactions, but zinc-containing representatives of aU enzyme classes are known, such as, for instance, alcohol dehydrogenase (an oxidoreductase), famesyl-Zgeranyl transferase (a transferase), -lactamase (a hydrolase), carbonic anhydrase (a lyase) and phosphomannose isomerase. 

The normal zinc content of the body amounts to 20-30 mmol (1.3-2.0 g). The daily dietary requirement is 10-15 mg. In the blood, zinc is bound to tt2-macro-globulin, albumin or amino acids, and a small amount is also bound to transferrin. Zinc is crucial to a variety of enzyme reactions. This applies especially to the liver. More and more attention has therefore been paid to the role of zinc in liver disease in recent years. Six enzyme groups (hydrolases, isomerases, ligases, lyases, oxidore-ductases and transferases) with a total of 35 zinc metal-loenzymes are listed. (98) Almost 200 enzyme reactions in the body are zinc-dependent ... 

We have already seen the diversity of function in the lyases, hydrolases, and oxidoreductases. Several other types of zinc coordination are found in a number of other enzymes, illustrated in Figure 12.12. These include enzymes with the coordination motif [(His)2(Cys) Zn " -OH2], found in the lysozyme of bacteriophage T7, or [(Cys)3 Zn " "-OH2] which occurs in 5-aminolaevulinate dehydratase (or porphobilinogen synthase). This latter enzyme catalyses the condensation of two molecules of 5-aminolaevulinate to form the pyrrole precursor of the porphyrins (haem, chlorophyll, and cobalamines), and its inhibition by Pb is the cause of lead poisoning (saturnism), frequently observed among inner city children (Chapter 1). 

More than 300 reactions are catalyzed by zinc-containing enzymes [82]. Zinc can be found with insulin, in the reproductive tract, in the DNA-binding proteins, and in oxidoreductases, transferases, lyases, isomerases, and ligases. 

One of the main biochemical roles of zinc is its influence on the activity of over 300 enzymes, which are distributed into the six classes oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. 

Lyases described in thermophilic bacteria include aldolase and citrate synthase. Freeze and Brock [303] reported on the aldolase in Thermus aquaticus from an evolutionary perspective. Enzyme activity was approximately doubled in the presence of manganese, nickel or zinc at low concentrations and EDTA inhibited the enzyme at micromolar concentrations. 

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