NORMAL FAT METABOLISM 209 



Knoop's hypothesis that the fatty acid chains are broken down two 

 carbon atoms at a time is supported by the following evidence (Knoop, F. 

 (a) 1904-05. Making use of benzol derivatives of the fatty acids which are 

 utilized with much more difficulty in the organism than the fatty acids 

 themselves, he found that the fatty acid side chains on the benzol nucleus 

 are broken down two carbon atoms at a time and that the breaking is pre- 

 ceded by oxidation at the (3-carbon atom. Oxidation of the fatty acids in 

 vitro usually takes place at the a-carbon atom, and Knoop's theory was re- 

 ceived skeptically by chemists until further work by Dakin confirmed his 

 results both on animals and in vitro, and indicated that (3-oxidation is prob- 

 al>ly the common type of oxidation of the fatty acids in the animal organ- 

 ism. The theory adequately explains the appearance, in diabetes and other 

 conditions, of (3-oxybutyric and its derivatives, which are regarded mainly 

 as residues of the fatty acids which have escaped complete combustion 

 because of an abnormality in metabolism. Later work has shown that 

 certain groups in the protein molecule may also form "acetone bodies," 

 but it is believed that this source is relatively unimportant. 



The fact that the fatty acids are broken down two atoms at a time 

 and the fact that naturally occurring fatty acids contain even numbers 

 of carbon atoms would render it probable that they were built up two 

 carbon atoms at a time, affording a basis for a theory of fatty acid syn- 

 thesis from carbohydrates in support of which there is considerable experi- 

 mental evidence. That fat is formed from carbohydrate has long been 

 known empirically since farm animals are ordinarily fattened on a diet 

 which consists mainly of starch; and scientifically acceptable proof was 

 furnished by Lawes and Gilbert many years ago. The probable mechanism 

 of the synthesis has been indicated by changes which take place readily 

 in carbohydrates. Thus sugars readily yield lactic acid by various treat- 

 ment action of bacteria, of weak alkalies, etc., and lactic acid in turn 

 breaks down readily to acetaldehyd. The acetic aldehyd by aldol con- 

 densation may be made to form (3-hydroxybutyric aldehyd, which by 

 shifting of the oxygen atom simultaneous oxidation and reduction 

 yields butyric acid. The butyric acid fermentation of dextrose or lactic 

 acid observed by Pasteur may probably be explained in this way. The 

 likelihood of this procedure being the true method of synthesis of the 

 fatty acids is rendered probable by the work of Kaper (1906-07), who 

 showed that in addition to butyric acid, caproic and caprylic acids are 

 formed, and that the synthesis of higher fatty acids may be brought about 

 in vitro from aldol and therefore from acetaldehyd. Smedley has raised 

 objections to the assumption that the higher fatty acids are formed from 

 acetaldehyd by aldol condensation, basing her objection on the fact that 

 the aldol condensation when applied to the higher aldehyds in vitro pro- 

 duces branched chains instead of straight chains, also that no free aldehyds 

 (except sugars) are found in the living organism. She suggests as the 



