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CHAPTER 31 



a blocked reaction, accumulate (as v+ sub- 

 stance accumulates in a cinnabar larva), and 

 can be used by a mutant that cannot form 

 these intermediates (as does a v disc implanted 

 in a en host). 



Subsequent work has confirmed these 

 hypotheses and has elucidated the specific 

 chemical nature of some of the substances 

 involved; these are indicated in the appro- 

 priate position in Figure 31-2B. It was 

 found, for example, that the v+ substance is 

 kynurenine, and that the cn+ substance is 

 3-hydroxykynurenine. Note that the v and 

 en genes apparently block adjacent reactions 

 in a sequence of reactions. You may ask 

 next, by what mechanism do these mutant 

 genes block these chemical reactions, or, con- 

 versely, by what means do the normal genes 

 v+ and c«+ accomplish the chemical conver- 

 sions into kynurenine and 3-hydroxyky- 

 nurenine, respectively. 



Kynurenine is converted to 3-hydroxyky- 

 nurenine by the addition of a hydroxyl (OH) 

 group. We can imagine two general ways 

 that c«+ could accomplish this. One might 

 involve the manufacture by c«+ of a unique, 

 not otherwise produced, hydroxyl-containing 

 substance capable of reacting with kynurenine 

 to produce its chemical conversion. The 

 other mechanism would presume that ky- 

 nurenine and this hydroxyl-containing com- 

 pound normally are both present in the same 

 cell but react together in the desired way 

 either not at all or with negligible frequency 

 in the absence of cn+. In this case, the pres- 

 ence of cr& would serve to expedite the chemi- 

 cal reaction, so it occurs with the required 

 frequency and speed. 



There are two unique features of cells 

 known to be involved in expediting (or hin- 

 dering) chemical reactions, features which are 

 absent from nonliving mixtures of chemical 

 substances. One of these involves the organi- 

 zation of certain cell components into struc- 

 tures {intracellular organelles) whose parts 

 have specific physical relationships to each 



other. It is possible that different genotypes 

 produce structural changes in the organelles 

 so that a chemical reaction which could take 

 place in one genotype is physically impossible 

 in another genotype, because the reactants 

 are spatially separated, and vice versa. The 

 second unique feature for the regulation of 

 metabolism in living material (protoplasm) 

 is the occurrence of enzymes, organic catalysts 

 which speed up chemical reactions between 

 other chemical substances. It is also possible, 

 then, that one genotype may have less, or 

 none, of an enzyme produced by another 

 genotype. Since many enzymes are known 

 to be located in, or to comprise part of, 

 organelles, it should be realized that a genetic 

 change might result in a change in both struc- 

 ture and enzyme simultaneously. It is also 

 possible that the manufacture of a unique 

 substance, which may be of a nonenzyme 

 nature, might affect cell structure and/or 

 enzyme formation. In fact, it is possible 

 that a change in any one of these three kinds 

 of effects could automatically involve the 

 others. 



Can we eliminate any of these three ex- 

 planations for gene action in the case of v+ 

 and cn+? Even though kynurenine is diffus- 

 ible between one cell and another, and there- 

 fore within a cell also, we cannot eliminate a 

 purely spatial change in the structure of some 

 organelle as the primary effect of the en mu- 

 tant. Moreover, it is also possible that en 

 fails to manufacture some unique hydroxyl- 

 containing substance to combine with ky- 

 nurenine, or that it fails to produce the specific 

 enzyme required to couple already present 

 hydroxyl to kynurenine. 



Let us discuss next the biochemical genetics 

 of certain traits in human beings, in the hope 

 that we may be able to obtain more evidence 

 concerning the mechanism whereby genes act 

 to direct the chemical activities of protoplasm. 

 There is a rare condition in man characterized 

 by the fact that, beginning at birth, the urine, 

 though normal in color when passed, soon 



