Enzyme relationship

Lederberg, J. (1956), Comments on the gene-enzyme relationship , in Gaebler, O. H. (Ed.), Enzymes Units of Biological Structure and Function, Academic Press, New York, pp. 161 -169. 

We are not concerned here with many of the details of genetic machinery. In higher organisms especially, the mechanisms are extremely intricate. Our discussion is by no means dependent upon the acceptance of any simple 1-gene-1-enzyme relationship, but it does rest upon the widely substantiated principle that the potentiality possessed by organisms for carrying out any and every chemical reaction arises from inheritance and intervening mutations. There is no other way in which such potentialities can arise. 

The only reasonable question of doubt with respect to individual variation of needs for B vitamins is this In mammals and specifically in human beings, how wide are the variations in needs In the following pages we will cite specific evidence with respect to several of the individual B vitamins. Each one, of course, has its own peculiar enzymic relationship and must be considered separately. 

Niacin requirements are dependent on the tryptophane supply and the ease with which the conversion of tryptophane to niacin can be made. Chickens and rats carry out the conversion readily. Dogs do so less readily. Monkeys and human beings carry out the process relatively ineffectively. Since this conversion involves several enzymatic steps, it is clear on the basis of gene-enzyme relationships why species differences exist. On the same basis inter-individual differences may be presumed to exist also. 

Beadle and Tatum deduced the one gene-one enzyme relationship. 

Hyal-1, an acid-active lysosomal enzyme, was the first somatic hyaluronidase to be isolated and characterized.191,192 It is a 57 kDa single polypeptide glycoprotein that also occurs in a processed 45 kDa form, the result of two endoprotease reactions. The resulting two chains are bound by disulfide bonds. This is not a zymogen-active enzyme relationship, since the two isoforms have similar specific activities. Why two forms should occur is unknown. Only the larger form is present in the circulation, while both isoforms occur in urine,193 in tissue extracts, and in cultured cells. Why an acid-active hyaluronidase should occur in plasma is not clear. Some species do not have detectable enzymatic activity in their circulation,194 but an inactive 70 kDa precursor form of the enzyme is present in such sera, detectable by Western blot (L. Shifrin, M. Neeman, and R. Stern, unpubl. data). Hyal-1 is able to utilize HA of any size as substrate, and generates predominantly tetrasaccharides. 

Detoxification Enzyme Relationships in Arthropods of Differing Feeding Strategies... 

More than 100 years ago (1894), Emil Fischer proposed a Key and Lock theory as to the specific substrate selectivity by the enzyme, which is presently understood as molecular recognition of the substrate by the enzyme through supramolecular interactions. If the enzymatic reaction takes place in vivo, it is always involved to recognize the substrate by the enzyme. This is also true for enzymatic reactions in vitro. However, readers will see in this article that the substrate—enzyme relationship is not as strict as the key—lock relationship, but enzymes are dynamic and sometimes very generous in recognizing even unnatural substrates in vitro. This situation allows enzymes to catalyze the synthesis of not... 

Table III. Acetolactate Synthase Gene-Enzyme Relationships...

Gene-Enzyme Relationships in the Purine Biosynthetic Pathway of Escherichia coli... 

Fig. 7. Intermediates and gene-enzyme relationships of tryptophan biosynthesis in Neurospora. Abbreviations PRPP, 5-phosphoribosyl-l-pyrophosphate PRA, N-(5 -phosphoribosyl) anthranilic acid CDRP, l-(o-carboxyphenylamino)-l-deoxyribulose-5-phosphate InGP, indole-3-glycerolphosphate PR, phosphoribosyl.

III. Gene-Enzyme Relationships in the Tryptophan Biosynthetic Pathway. 392... 

III. GENE-ENZYME RELATIONSHIPS IN THE TRYPTOPHAN BIOSYNTHETIC PATHWAY... 

Fio. 3. Gene-enzyme relationships in the tryptophan pathway of bacteria. The gene designated by a question mark represents a possible location (inferred from mapping distances) of the gene coding for the smaller protein component of AS in P. putida. The gene has not yet been identified by a specific mutational defect. Dashed lines represent relationships whose existence are still in question. See the text for further explanations. 

Tentative gene-enzyme relationships in the tryptophan biosynthetic pathway of B. subtilis are shown in Fig. 3. Early studies indicating that... 

There is currently some uncertainty about the complexity of the tryptophan gene-enzyme relationships in B. subtilis. Whitt and Carlton [46,47] have noted pleiotropic effects. Most recently [46] they have found that the pleiotropy is limited to elimination of InGPS activity by mutations in either the trpD or trpF genes, which are primarily concerned with PRT and PRAI activity, respectively. The pleiotropic effects are shown in Fig. 3 by dotted lines and may indicate that the enzymes function as aggregates in vivo or may represent effects on translation similar to polarity effects. Hoch et al. [48], on the other hand, have not found these pleiotropic effects and report essentially one gene-one enzyme activity [when the individual activities of the tryptophan synthetase a and p2 subunits (Fig. 1) are included]. The nonconformity in the results of different investigators may be due to the use of different mutants and to different methods of preparation, affecting enzyme stabilities. 

Young IG, Stroobant P, Macdonald CG, Gibson E (1973) Pathway for ubiquinone biosynthesis in Escherichia coli K-12 gene-enzyme relationships and intermediates. J Bacteriol 114 42-52... 

Bonner, D. M. (1951) Gene-enzyme relationships in Neurospora. Cold Spring Harb. Symp. on Quant. Biol. 16, 143-157. 

Armed with these new insights into primary, secondary, tertiary, and quaternary structure of proteins, let us now return to the question of the relation one gene-one polypetide. In doing so we will not concern ourselves with the enumeration of instances of one gene-one enzyme relationships. (There is a variety of obvious examples in higher plants.) Instead we want to verify whether in fact one gene does induce one polypeptide, which can then, possibly, combine with other polypeptides of the same or a slightly different kind to form a quaternary structure. To do this we must study isoenzymes. 

The discovery of the mouse renal /3-glueuronidase response to androgens provided a very useful phenomenon which has been studied extensively as an example of the hormone-enzyme relationship (Fishman and Farmelant, 1953). 

In considering the commercially successful herbicides known to be inhibitors of amino acid biosynthesis, three aspects will be considered the kinetic description of the inhibition, the molecular interactions involved, and the relevance of the proposed target site to the observed physiological effects. Because of the extensive body of research published on the shikimate pathway and the herbicide glyphosate, this example will be taken as a paradigm of the inhibitor-enzyme relationship. The other cases considered will be the branched-chain amino acid family, histidine biosynthesis, and glutamine synthetase. 

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