66 II. BIOSYNTHESIS 



ethanolamine and of dimethylethanolamine to choline, D-methionine is 

 considerably more efficient as a methyl donor than is the L- form of this 

 amino acid. Ethanolamine is also methylated by betaine, or by other 

 lipotropic substances, acting as methyl donors. However, the betaine 

 molecule is not converted as a whole to choline.^** 



Barrenscheen and Skudrzyk*^^ confirmed the fact that ethanolamine 

 and serine are the methyl acceptors, and that a lyo-enzyme, liver pherase, 

 brings about the methylation by methionine. The enzyme system is active 

 in liver homogenate; it was found to be inhibited by ascorbic acid. Methi- 

 oninesulfoxide (CH3S:OCH2CH2CH(NH2)COOH) was found to be the 

 first intermediary product formed by aerobic action on methionine. Arn- 

 stein^^^ likewise demonstrated that serine, methanol, sodium formate, 

 and glycme all give rise to choline labeled both in the methyl groups and 

 in the ethanolamine residue. Only carboxyl-labeled glycine failed to 

 transfer the label to choline; this is interpreted as indicating that glycine is 

 converted to ethanolamine via serine, under which condition the carboxyl 

 group of glycine is lost. On the other hand, Weinhouse, Millington, and 

 Strassman-^" demonstrated that the methylene carbon of glycine can give 

 rise to the chohne methyl group. 



Some information as to the intermediates involved in the methylation 

 of ethanolamine can be obtained from the experiments of Horowitz^^^ 

 with certain strains of the red bread mold, Neurospora crassa, which have 

 lost their capacity for effecting a synthesis of choline. One variant of 

 Neurospora was shown to have lost its power to synthesize choline at a 

 stage preceding monomethylaminoethanol (CHa-NH- CH2 • CH2OH), while 

 the block in the second strain followed this compound. These results 

 prove that monomethylaminoethanol is a normal intermediate in the syn- 

 thesis of choline by Neurospora, and presumably by higher species. 



Stekol et al.^^^ reported that the incorporation of the methyl group of 

 methionine and of betaine into tissue cholme was reduced m folic acid de- 

 ficiency. On the other hand, a deficiency of vitamin B12 had no effect on 

 transmethylation. When vitamin Be (pyridoxine) was deficient, the in- 

 corporation of the methyl group from methionine mto choline was reduced, 



334 V. du Vigneaud, S. Simmonds, J. P. Chandler, and M. Cohn, J. Biol. Chem., 165, 

 639-648(1946). 



"5H. K. Barrenscheen and I. Skudrzyk, Z. physiol. Chem., 284, 228-236 (1949). 



336 H. R. V. Arnstein, Biochem. J., 47, xviii-xix (1950). 



3" S. Weinhouse, R. H. Millington, and M. Strassman, /. Avi. Chem. Soc, 73, 1421- 

 1423 (1951). 



338 N. H. Horowitz, /. Biol. Chem., 162, 413-419 (1946). 



333 J. A. Stekol, S. Weiss, P. Smith, and K. Weiss, /. Biol. Chem., 201, 299-316 (1953). 



