Enzyme metal linkage

We next focus on the use of fixed-site cofactors and coenzymes. We note that much of this coenzyme chemistry is now linked to very local two-electron chemistry (H, CH3", CH3CO-, -NH2,0 transfer) in enzymes. Additionally, one-electron changes of coenzymes, quinones, flavins and metal ions especially in membranes are used very much in very fast intermediates of twice the one-electron switches over considerable electron transfer distances. At certain points, the chains of catalysis revert to a two-electron reaction (see Figure 5.2), and the whole complex linkage of diffusion and carriers is part of energy transduction (see also proton transfer and Williams in Further Reading). There is a variety of additional coenzymes which are fixed and which we believe came later in evolution, and there are the very important metal ion cofactors which are separately considered below. 

Several other major classes of enzymes, among them the nucleic acid polymerases, activate ATP (and other NTPs) in a completely different manner. Similar to transphos-phoiylation enzymes, they utilize two metal ions for catalysis. However, steric interactions are purposely employed in order to reverse the preferred binding situation. A MaMp y motif is generated which weakens the P —O—P,5 linkage This allows a nucleoside monophosphate group to be transferred (under liberation of PPi), a process which is essential in the biosynthesis of DNA and RNA sequences. 

Proteins are polymers produced from amino acids that are joined by peptide linkages (amine-group carboxylic acid bonds). These compounds form the bulk of living tissue. Enzymes, those very selective and powerful catalysts, are also proteins. Enzymes may contain a group based on a metal atom, as may molecules from other classes of compounds (hemoglobin, chlorophyll, etc.). Some proteins serve special functions, such as hemoglobin, an oxygen carrier. 

The other major enzymes in pancreatic juice of relevance to our discussion are the nucleases. Human pancreatic DNase I has a molecular weight of around 30 kDa, shows maximal activity in the pH range 7.2-7.6 and requires metal ions such as Mn+, Mg+ or Co+ in the presence of Ca+. It is an endonuclease that hydrolyses the phosphodiester linkages in both single- and double-stranded DNA at multiple sites (Funakoshi et al. 1977 Takeshita et al. 2000). 

The terms cofactor, coenzymes, and prosthetic group are used to describe the nonprotein moieties of the enzyme active center. The distinction between these terms is not sharp. Some of the cofactors are derivatives of vitamins that form either covalent or noncovalent linkages at or near the active site of the enzyme, and some are metal ions. If a cofactor (coenzyme) is tightly bound to the protein moiety (the apoenzyme), it is often referred to as a prosthetic group. A coenzyme that is easily removed from the holoenzyme, leaving behind the apoenzyme, is often regarded as a second substrate. 

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