Analogous enzymes and coenzymes

Many examples are known where the enzymes carrying out apparently identical functions, in dissimilar cells or dissimilar genera, are themselves dissimilar. When the chemical differences between the two enzymes is small, we speak of isoenzymes but when it is much larger, they are called analogous enzymes. 

There are two distinct classes of the enzymes known as FDP (fructose 1,6-diphosphate) aldolases, which carry out an important and early stage in glycolysis (a), the varieties found in animals and higher plants cleave FDP byway of a Schiff base, whereas (b), those which occur in bacteria and fungi require a metal (usually Zn ) bound to the carbonyl group in the enzyme-substrate complex special inhibitors exist for the second variety (Lewis and Lowe, 1973). More examples of differing metal requirements will be found in Section 11.1 see under Helminths in Section 4.4 for some other differences in analogous enzymes. 

The ability of various diaminopyrimidines to distinguish between analogous forms of the enzyme dihydrofolate reductase is the basis of some of the best contemporary anti-malarial and anti-bacterial therapy (see Section 4.0, p. 123, Tables 4.1 and 4.2, and Section 9.3.3 and 9.6). Let us first look at the differences that exist between various vertebrate types of the enzyme, none of which is much inhibited by trimethoprim (4.P), and then proceed to invertebrate types, which are highly susceptible to this drug. The enzyme from chicken liver has only 75% identity of amino acid sequence with that from ox liver. Moreover, methylmercuric hydroxide activates the avian type twelvefold whereas it inactivates the bovine type. The avian type is much richer in basic amino acids and has an isoelectric point of 8.4 compared to 6.8 for the bovine type. This result is achieved in the avian type by the presence of lysine at positions 32,106, and 154, whereas the bovine type has glycine, threonine, and glutamic acid, respectively, in these positions (Kumars/a/., 1980). 

No matter what the source of dihydrofolate reductase (DHFR), there is an acidic group in (or near) the 27th residue for instance, in E. coli this is Asp-27. In fact it is always aspartic acid for prokaryotic forms, but glutamic acid for eukaryotic forms. This seems an important difference, because it is the aspartic acid residue in the prokaryotic enzyme that binds to the 2-NH2 of 2,4-diamino-pyrimidine inhibitors (Bolins/a/., 1982). 

DFR from vertebrate sources has the residue Tyr-31 in place of the less less bulky Leu-27 of the bacterial enzymes these residues line the pocket in which the pteridine nucleus has to fit in each case. Vertebrate enzymes, which have about 185 residues, are larger than those of bacteria with about 165 residues. How this difference comes about is seen in chicken liver enzyme which has three extra loops on the edge of the pleated sheet, all of them free from normal interchain hydrogen-bonding (Volz etal., 1982). Unlike bacterial DFR, mammalian DFR can reduce folate as well as dihydrofolate. 

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