164 SECTIONAL ADDRESSES. 



stronger. Yet it has not been demonstrated either in vitro or in vivo that 

 thyroxine may be produced from diiodotyrosine. 



These two instances of adrenaline and thyroxine show that even when 

 there is a reasonable presumption that we know the raw material from 

 which the synthesis in the cell starts and the chemical processes concerned 

 the proof that our hypotheses are correct is far from simple. 



We may now pass on to consider a process in which the raw material 

 is known with certainty but the chemical reactions by which the synthesis 

 takes place are relatively obscure. I refer to the production of fat from 

 carbohydrate. Lawes and Gilbert in their classical experiments at 

 Rothamsted on the fattening of farm stock, showed indubitably that 

 animals can produce fat from starch. It has been confirmed since by 

 others. Since the starch is converted into glucose in the alimentary canal 

 prior to absorption we may consider glucose as the starting point of the 

 synthesis. 



It involves the production from hexose units of straight carbon chains 

 of 16, 18 and 20 or more carbon atoms such as are found in the naturally- 

 occurring, higher fatty acids. The carbon atoms are present in even 

 numbers and the carbon chains may be completely saturated or partly 

 unsaturated. Any series of reactions which is put forward to explain 

 this synthesis must therefore take into account these elementary facts if 

 no others. The origin from carbohydrate at first sight suggests the coup- 

 ling of hexose units end to end although this would only suffice to explain 

 the production of acids containing multiples of six carbon atoms such as 

 stearic and oleic acids. Such a scheme was put forward many years ago 

 by Emil Fischer but has not found general acceptance. Apart from the 

 difficulty of explaining the production of acids that do not have eighteen 

 but some other even number of carbon atoms, it has never yet been shown 

 that hexose molecules unite end to end using any of the usual methods 

 which bring about the condensation of aldehydes. It is therefore impro- 

 bable from the purely chemical point of view. 



A more likely chemical explanation of the origin of the fatty acids is 

 that they are built up, two carbon atoms at a time from some simple, 

 reactive substance which is first produced by degradation of glucose. 

 Acetaldehyde and pyruvic acid have both been suggested as probable 

 participants in a reaction of this kind, the former condensing with itself, 

 as in the well known aldol condensation, the latter either with acetaldehyde 

 or with some higher aldehyde containing an even number of carbon atoms 

 produced in the earlier stages of the reaction. By both of these methods 

 it has been shown that in vitro aldehydes with an even number of carbon 

 atoms in a straight chain can be built up step by step and these by oxida- 

 tion can be readily converted into the corresponding fatty acids. Un- 

 saturated linkages in the chain may be produced by either method so that 

 this requirement in the hypothetical synthetic method is also satisfied. 

 Further, the condensation takes place in weakly alkaline solution or under 

 the catalytic influence of certain organic bases, so that drastic treatment 

 is not necessary to bring about the reaction. So far this evidence for the 

 mechanism of synthesis of the fatty acids is purely chemical and the 

 grounds on which it can be put forward are largely chemical ones. Is 

 there any physiological support for this scheme ? Studies of the synthesis 



