METABOLISM. 347 



phorus), and in some diseases, the combination of fat with the rest 

 of the protoplasm is broken, and the fat is set free in such a form that 

 it can be stained and recognised under the microscope. This change, 

 which is called fatty degeneration, was formerly believed to be the 

 result of the formation of fat from protein. Chemical analysis of such 

 an organ shows, however, that it contains no more fat than would 

 be found in a healthy organ. Hence fatty degeneration implies, not 

 the formation of fat from protein, but merely the setting free in a 

 visible form of previously combined fat. 



The fat is normally completely oxidised in the tissues to carbonic 

 acid and water; the nature of the changes taking place is not fully 

 understood, but in all probability the long chain of carbon atoms 

 constituting a fatty acid is broken down in stages, two carbon 

 atoms being split off at each stage. The complete oxidation of fat, 

 however, is dependent upon the presence of carbohydrate in the 

 tissue cells. 



Acidosis. When the tissues are deprived of carbohydrate, for ex- 

 ample during starvation or on a diet free from carbohydrate, the oxida- 

 tion of fat is incomplete, and intermediate metabolic products are formed 

 in the tissues and pass into the blood and urine. These products are 

 /2-oxybutyric acid, aceto-acetic (diacetic) acid, and acetone, their 

 chemical relationship being shown as follows : 



CHg ^^3 ^Ho 



I I I 



CHOH CO CO 



I -* I -> 

 CH 2 CH 2 CH 3 



COOH COOH 



/3-oxybutyric acid Aceto-acetic Acetone 



acid 



There is evidence that /?-oxy butyric acid and aceto-acetic acid are 

 normally formed in the body during the metabolism of fat, but are 

 fully oxidised ; in the absence of carbohydrate they pass into the blood 

 stream, and aceto-acetic acid, instead of undergoing oxidation, is con- 

 verted into acetone. The origin of these bodies from fat is clearly 

 shown by the observation that when the diet consists solely of fat their 

 amount in the urine may become very large. /3-oxybutyric acid and 

 its products are formed to some extent at least in the liver. 



The presence of these substances in the blood and urine is known as 

 acidosis, and is an indication, whenever it occurs, that the supply of 

 carbohydrate to the tissues is inadequate. In the blood /?-oxybutyric 

 acid and diacetic acid combine with ammonia which would otherwise 



