I.— PHYSIOLOGY. 163 



substance is obtained. It is not possible to say as yet whether this is 

 adrenaline. The amount produced represents only a small proportion of 

 the reaction products, but it brings nearer the possibility that a methylated 

 tyrosine by simple oxidation under the influence of an enzyme might give 

 rise to adrenaline by the following scheme of reactions : — 



CHa • CH(NHCH,) • COOH CHg • CH(NHCH3) ■ COOH 



'o 



OH 



N-methyltyroaine 3 : 4 quinone of N-methylphenylalanine 



CHOH • CH.2(NHCH3) 



'OH 

 OH 

 Adrenaline 



If, however, we consider how we may find out whether a process of this 

 kind, operating in the cells of the adrenal gland under specific conditions, 

 gives rise to adrenaline, many difficulties appear. One method of approach 

 would be to find the conditions under which a production of adrenaline by 

 the medullary cells of the gland occurs and then under these conditions 

 determine whether introduction of tyrosine or possible intermediate pro- 

 ducts in the synthesis leads to an increased formation. But these condi- 

 tions are not as yet defined. Attempts have been made by exposing the 

 glands freshly removed from the body to solutions of tyrosine but no 

 production of adrenaline has been demonstrated. Neither is there any 

 evidence that the cells of the gland can either oxidise tyrosine in the same 

 way that the enzyme tyrosinase does, or methylate it. The possibility has 

 to be borne in mind also that even if tyrosine be the mother substance of 

 adrenaline the processes requisite to produce adrenaline from it may not all 

 take place in the adrenal gland. In that case the efiect of hypothetical 

 intermediate products on adrenaline formation would have to be tried. But 

 methods of this kind are relatively crude. If they fail it does not neces- 

 sarily mean that the hypothesis as to the gross chemical mechanism is 

 wrong. When we remember that the oxidation of one substance may 

 only take place if another is reduced ; that a reaction taking place in one 

 compound may only be possible when some other reaction takes place 

 along side it, in other words, that in the living cell there is a continuous 

 and complex interplay of chemical reactions ; then it is not surprising 

 that the discovery of the mechanisms by which adrenaline is formed, 

 although a simple problem at first sight, is probably in reality very com- 

 plicated. 



The case of thyroxine is comparable with that of adrenaline. Thyroxine 

 is a relatively simple chemical substance which could conceivably be 

 produced by the oxidation of diiodotyrosine. The last named compound 

 has recently been shown to be present in the thyroid gland and this makes 

 the presumption that it is the mother substance of thyroxine all the 



M 2 



