ANIMAL METABOLISM 339 



From this, in turn, are formed acetone and ^S-hydroxybutyric acid: 



+ 2(H) _ 



CHaCHOHCHjCOOH (34)^ CHsCOCH.COOH -^^ CH3COCH, 

 |3-Hydroxy butyric acid " ^^^ Acetoacetic acid Acetone 



These three substances collectively are called "ketone bodies." When 

 fat, but not carbohydrate, is metabolized, the ketone bodies accumulate 

 in the blood and are excreted in the urine. This condition is called 

 ketosis. Since two of the ketone bodies are acids, ketosis also involves 

 a condition of acidosis, which if not relieved, leads to coma and death. 



Ketosis may be caused by eating a diet high in fat and low in carbo- 

 hydrate. For most people a diet having over 75 per cent of the calories 

 in the form of fat and less than 15-20 per cent as carbohydrate is keto- 

 genic (i.e., produces ketosis). However, Eskimos, for example, can tol- 

 erate even higher amounts of fat. Ketosis may also develop during 

 starvation or after long-continued vomiting, because in such cases the 

 main food material being metabolized is the stored fat. Diabetics are 

 very apt to develop ketosis because of their lowered ability to metabolize 

 sugars. The excretion of ketone bodies in cases of ketosis in human 

 beings often amounts to 15-20 g. per day and has been reported in 

 extreme cases to be more than 100 g. per day. 



The exact manner in which acetoacetic acid is formed in ketosis has 

 been the subject of much dispute. Formerly, it was thought to arise 

 only from the four carbon atoms at the methyl end of fatty acid mole- 

 cules, i.e., the last to be degraded by normal yi9-oxidation. However, it 

 was later found that enzymatic oxidation of caprylic acid (the saturated 

 C-8 acid) gave rise to tivo moles of acetoacetate. The /^-oxidation theory, 

 of course, could account for only one mole from one mole of the fatty 

 acid. It was found further that if the caprylic acid were labeled with 

 C^^, a heavy isotope of carbon, in the — COOH group, the C^^ appeared 

 in both the — COOH and CO groups of the acetoacetic acid. These 

 experimental findings showed that, at least in this case, the caprylic 

 acid was first oxidized to C2 fragments, which then recombined as indi- 

 cated in reaction 32 above. 



Other metabolic reactions of acetic acid 



Fat Synthesis. It is a matter of common observation that consump- 

 tion of excess food leads to fatness. Fat can be synthesized in the animal 

 body from either carbohydrates or proteins, although the carbohydrates 

 are the only important source. 



The production of fat from carbohydrate is a process of reduction 

 and requires energy. Part of the sugar must be oxidized in order that 

 the rest may be converted into fat. Although the mechanism of the 

 conversion is not positively known, the sugar is probably broken down 



