270 VI. ACETIC, FORMIC, AND PROPIONIC ACIDS 



acids and cholesterol.^^ This synthesis occurs without the intermediary 

 formation of carbohydrate. The variation in the enzyme systems required 

 to effect these syntheses is indicated by the fact that, in the presence of 

 sulfite, steroid formation is inhibited, ^-^ while that of fatty acids is un- 

 affected. It is suggested that acetaldehyde might be the intermediate in 

 cholesterol synthesis, while acetate might condense directly on the fatty 

 acid chain. In the case of yeast, Sonderhoff and Thomas^^^ noted that 

 deuterioacetate was metabolized in such a way as to indicate that carbo- 

 hydrate is not an intermediate in the hpid synthesis from acetate. The 

 mechanism of synthesis of fatty acids from acetate and its relation to CoA 

 are discussed at length on pages 10 to 26. 



c. Cholesterol Synthesis. In the synthesis of the unsaponifiable fraction 

 in yeast from deuterioacetate, Sonderhoff and Thomas'^^ noted that the 

 deuterium concentration was twice as high as in the fatty acid fraction, 

 and twenty times that in the yeast carbohydrate. These results are also 

 interpreted to indicate that the synthesis of the yeast steroids proceeds 

 directly. The detailed discussion of the mechanism of cholesterol syn- 

 thesis is given in Chapter VIII. 



d. Protoporph5rrin Synthesis. Bloch and Rittenberg^^ reported that 

 hemin isolated from the red blood cells of animals which received deuterio- 

 acetate contained appreciable amounts of deuterium. Since the proto- 

 porphyrin moiety of hemoglobin is synthesized at a relatively slow rate, 

 the isotope concentration in hemin is of a low order in short-term feeding 

 tests. '2'* However, when the feedmg is continued over several weeks, the 

 concentration of deuterium in the hemin reaches a level which is 50% of 

 that in the acetic acid available in the metaboHc pool. According to 

 unpublished work of Bloch and Rittenberg cited by Bloch, ^ at least one- 

 half of the hydrogen atoms in the porphyrin molecule originate from acetic 

 acid. 



Although the above experiments prove that acetate is a source of carbons 

 in the protoporphyrin molecule, they do not indicate which parts of the 

 molecule are involved. Since no hydrogens are attached to the carbons 

 of the pyrrole rings, it is not possible to determine whether or not acetate 

 enters the pyrrole ring structure. However, carbon-bound hydrogen occurs 

 in the methine bridges which link the pyrrole rings, as well as in the pyrrole 

 side chains. Bloch ^ is of the opinion that the acetate molecule enters into 



1" I. Smedley-MacLean and D. Hoffert, Biochem. ./., 20, 343-357 (1926). 

 1" R. Sonderhoff and H. Thomas, Ann., 530, 195-213 (1937). 



124 D. Shemin and D. Rittenberg, /. Biol. Chem., 159, 567-568 (1945); 166, 621-625 

 (1945). 



