OcToBER 16, 1913] 
NATURE 
219 
in the removal of the amino group is not a simple 
reduction, which would yield a fatty acid, or substi- 
tuted fatty acid, nor a hydrolytic removal which would 
leave an a-hydroxy-acid; but the much less to be 
expected process of an oxidative removal, which re- 
sults in the production of a keto-acid.* If the direct 
evidence for this chemically most interesting primary 
change were to be held insufficient (though there is 
no insufficiency about it), its physiological reality is 
strongly supported by the proof given us by Knoop 
and Embden that the liver can  resynthesise the 
original amino-acid from ammonia and the corre- 
sponding keto-acid. This profoundly significant 
‘observation is part of the evidence which is continu- 
ally accumulating to show that all normal chemical 
‘processes of the body can suffer reversal. The next 
‘step in the breakdown involves the oxidation of the 
keto-acid, with the production of a fatty acid contain- 
ing one carbon less than the original amino-acid. 
This in turn is oxidised to its final products along 
the lines of the B-oxidation of Knoop, two carbon 
atoms being removed at each stage of the breakdown. 
‘All this is true of the aliphatic a-amino-acids, and, 
with limitations, of the side chains of their aromatic 
congeners. In the case of certain amino-acids the 
course of breakdown passes through the stage of 
-aceto-acetic acid. This happens to those of which the 
molecule contains the benzene ring, and Dakin has 
enabled us to picture clearly the path of change which 
involves the opening of the ring. This particular 
stage does not seem to occur in the breakdown of the 
aliphatic amino-acids, save in the case of leucin; the 
rule and the exception here being alike easy of ex- 
planation by considerations of molecular structure. 
But direct breakdown on the lines mentioned is far 
from being the only fate of individual amino-acids in 
the body. The work of Lusk, completed by that of 
Dakin, has shown us that of seventeen amino-acids 
derived from protein no less than nine may indi- 
vidually yield glucose in the diabetic organism, and 
there are excellent grounds for believing (indeed, there 
is no doubt) that they do the same to a duly regulated 
extent in the normal organism. The remaining seven 
have been shown not to yield sugar, and there is 
therefore a most interesting contrast in the fate of 
two groups of the protein Bausteine. Those which 
yield sugar do not yield aceto-acetic-acid, and those 
which yield the latter are not glycogenic. One set, 
after undergoing significant preliminary changes, 
seems to join the carbohydrate path of metabolism, 
the other set ultimately joins a penultimate stage in 
the path which is traversed by fats. 
I will here venture to leave for one moment the 
firm ground of facts experimentally ascertained. Un- 
_ explored experimentally, but quite certain so far as 
_ their existence is concerned, are yet other metabolic 
_ paths of prime importance, along which individual 
amino-acids must travel and suffer change. We know 
_ now from the results of prolonged feeding experi- 
_ ments upon young growing animals, which I myself, 
as well as many others, have carried out, that all the 
_ nitrogenous tissue complexes, as well as the tissue 
_ proteins, can be duly constructed when the diet con- 
tains no other source of nitrogen beside the amino- 
acids of protein. The purin and pyrimidin bases, for 
instance, present in the nuclear material of cells cer- 
tainly take origin from particular amino-acids, though 
we have no right to assume that groups derived from 
carbohydrates or fats play no part in the necessary 
_ syntheses. While recent years have given us a 
2 Dakin’s recent work is giving us an insight into the mechanism of the 
_ keto-acid formation. Amino-acids in aqueous solution dissociate into 
_ ammonia and the corresponding keto-aldehyde. The oxidation involved is 
therefore concerned with the conversion of the aldehyde into the acid. 
NO. 2294, VOL. 92] 
wonderfully clear picture as to how the nucleic acids 
and the purin bases contained in them break down 
during metabolism, we have as yet no knowledge of 
stages in their synthesis. But it is clear that to dis- 
cover these is a task fully open to modern experi- 
mental methods, and though a difficult problem, it 
is one ready to hand. Again, in specialised organs 
substances are made which are of great importance, 
not to the structure, but to the dynamics of the body. 
These have become familiar to us under the name of 
Hormones. We know the constitution of one of these 
only, adrenaline. The molecule of this exemplar has 
a simple structure of a kind which makes it almost 
certain to be derived from one of the aromatic amino- 
acids. It is clearly open to us to discover on what 
lines it takes origin. Facts of this kind, we may be 
sure, will form a special chapter of biochemistry in 
the future. I would like to make a point here quite 
important to my main contention that metabolism 
deals with simple molecules. As a pure assumption 
it is often taught, explicitly or implicitly, that although 
the. bowel prepares free amino-acids for metabolism, 
only those which are individually in excess of the 
contemporary needs of the body for protein are directly 
diverted to specialised paths of metabolism, and these 
to the paths of destructive change. All others—ali 
those which are to play a part in the intimacies of 
metabolism—are supposed to be first reconstructed 
into protein, and must therefore again be liberated 
from a complex before entering upon their special 
paths of change. But there is much more reason 
(and some experimental grounds) for the belief that 
the special paths (of which only one leads to the repair 
or formation of tissue protein) may be entered upon 
straightway. Mrs, Stanley Gardiner (then Miss Will- 
cock) carried out some feeding experiments a few 
years ago, and in discussing these I pointed out that 
they offered evidence of the direct employment for 
special purposes of individual amino-acids derived as 
such from the bowel. It seemed at the time that the 
argument was misunderstood or felt to carry little 
weight, but later Prof. Kossel (Johns Hopkins fios- 
pital Bulletin, March, 1912) quoted my remarks with 
approval and expressed agreement with the view. that 
the Bausteine of the food protein must, in certain 
cases, be used individually and directly. 
I wish I had time to illustrate my theme by some 
of the abundant facts available from quite other de- 
partments of metabolism; but I must pass on. 
The chief thing to realise is that as a result of 
modern research the conception of metabolism in 
block is, as Garrod puts it, giving place to that ot 
metabolism in compartments. It is from the be- 
haviour of simple molecules we are learning our most 
significant lessons. 
Now interest in the chemical events such as those 
we have been dealing with may still be damped by 
the feeling that, after all, when we go to the centre 
of things, to the bioplasm, where these processes are 
initiated and controlled, we shall find a milieu so com- 
plex that the happenings there, although they com- 
prise the most significant links in the chain of events, 
must be wholly obscure when seen from the point of 
view of structural organic chemistry. I would like 
you to consider how far this is necessarily the case. 
” The highly complex substances which form the most 
obvious part of the material of the living cell are 
relatively stable. Their special characters, and in 
particular the colloidal condition in which they exist, 
determine, of course, many of the most fundamental 
characteristics of the cell: its definite yet mobile 
structure, its mechanical qualities, including the con- 
tractility of the protoplasm, and those other colloidal 
characters which the modern physical chemist is 
