542 THE LIVER [CH. XXXV. 



which are next found in the cells of other organs throughout the 

 body disintegrate, probably where the un saturated links have been 

 introduced, and the lower acids so formed by successive oxidations 

 break down to molecules of the size of acetic acid, and are lastly 

 completely burnt to carbonic acid and water. 



Acidosis. This condition is seen in diabetes; poisonous acids 

 in the blood produce a state of coma, or deep unconsciousness, which 

 may finally cause death. For a diabetic is not only unable to burn 

 and so utilise carbohydrate, but he fails in a similar way in his 

 utilisation of fat. Butyric acid and /3-hydroxybutyric acid are prob- 

 ably normal intermediate products in fat katabolism, but a healthy 

 man on a normal diet is able still further to oxidise them into 

 carbonic acid and water. But on an abnormal diet, for instance, 

 when carbohydrate food is absent, fat-cleavage largely stops short 

 at the hydroxybutyric acid stage; consequently this and possibly 

 other related fatty acids accumulate and cause acidosis ; this condi- 

 tion is increased the more fat is given in the food, and the acidosis 

 of diabetes is similarly increased by fatty food. These poisonous 

 acids were once believed to originate from proteins; if that weie 

 so there ought to be an increase of other protein katabolites in 

 the urine, which there is not. The acids decrease the alkalinity and 

 carbonic acid of the blood, and the ammonia of the urine is increased ; 

 this indicates an attempt of the body to neutralise the acids. 



The hydroxybutyric acid does not pass entirely unchanged into 

 the urine. /3-Hydroxybutyric acid is CH 3 . CHOH. CH 2 . COOH. 

 By oxidation, the two hydrogen atoms in thick type are removed 

 to form water, and this leaves CH 3 . CO . CH 2 . COOH, which is aceto- 

 acetic acid : when the COO in thick type is removed we get 

 acetone (CH 3 . CO . CH 3 ), which gives the breath and urine of such 

 patients an apple-like smell. 



In these changes the liver plays an important part by means 

 of certain enzymes which Dakin has proved to exist. One enzyme, 

 called fi-hydroxy'butyrase, is an oxidase; it oxidises the /3-hydroxy- 

 butyric into aceto-acetic acid, and its action is increased by the 

 addition of blood or oxyhaemoglobin, which furnishes the necessary 

 oxygen. It probably is active in health as well as in disease, the 

 aceto-acetic acid being finally burnt into carbonic acid and water. 

 The other enzyme which forms acetone is not an oxidative one, and 

 acetone formation probably never occurs in the healthy state. 



Pat Synthesis. So much for the relationship of the liver to fat 

 katabolism; but it appears that the liver is also important in the 

 building up of fats, especially of those complex fats called phospha- 

 tides. It is, however, possible that this is not exclusively the property 

 of liver cells : when once the desaturated acids are supplied by the 

 liver, each organ can make its own phosphatides for itself. 



