IV BIOSYNTHESIS OF AMINO ACIDS 59 



was thereafter demonstrated by Sakami and by Greenberg and coworkers. The 

 latter investigators showed that rat liver slices converted glycine-2-''*C to both the 

 alpha and the beta carbon of serine. Likewise, beta labelled serine could be formed 

 from formate-'''C and unlabelled glycine in liver slices or in the intact rat (Sieke- 

 vitz and Greenberg, 1949; Sakami, 1948). Pyridoxal phosphate and tetrahydrofolic 

 acid derivatives are cofactors in the interconversion of glycine and serine (Kisliuk 

 and Sakami, 1955; Alexander and Greenberg, 1955, 1956). It has been postulated 

 that pyridoxal phosphate forms a Schiff base with glycine, thereby activating the 

 methylene carbon atom of glycine (Fig. 20). Also, tetrahydrofolic acid functions 

 as an acceptor of formate or HCHO in numerous one carbon transfer reactions 

 including the synthesis of serine from glycine and formate (Kisliuk and Sakami, 

 1955; Blakeley, 1954). Reactions one to eight have been demonstrated with en- 

 zymes of pig liver (Jaenicke, 1955): 



ATP 



i) Formate-i^C + THFA > NioTormyl-i^C (THFA) 



2) Serine-3-'-'C -t- THFA -> Nio-Formyl-'-'C (THFA) + glycine 



3 TPNH2 



3) '•'C-Formyl (folic) + glycine >■ serine-3-i-'C ^ THFA 



DPNH2 



4) Nio-Formyl-i^C (THFA) ^ glycine * serine-3-i-«C + THFA 



5) THFA + serine-^ N'o-hydroxymethyl (THFA) + glycine 



6) N'o-Formyl (THFA) -r TPNH, -> Nio-hydroxymethyl (THFA) + TPN* 



TPN" 



7) N'o-Formyl (THFA) + THFA > Dihydrofolic + Ni°-(hydroxymethyl) THFA 



ATP 



8) Formate + glycine > serine 



DPNH2 

 THFA 



ATP is required in reaction i ) and reaction 8) in order to activate the formate. 

 Reduced TPN is needed to convert folic acid to tetrahydrofolic acid in reactions 

 3) and to convert N^°-formyl tetrahydrofolic acid to N^^'-hydroxymethyltetra- 

 hydrofolic acid (reaction 6). N^'^-formyltetrahydrofolic acid serves as an "active 

 formyl" group donor in the formation of inosinic acid or in the synthesis of carbon 

 two of the imidazole ring of histidine (Jaenicke, 1955). See Fig. 20. 



There is reason to believe that the natural coenzyme is a polyglutamate rather 

 than a monoglutamic acid derivative of folic acid. Polyglutamates of folic acid 

 act catalytically in stimulating the conversion of serine to glycine by Clostridium 

 enzymes under conditions where monoglutamyl folic acid compounds are either 

 inactive or active only at substrate concentrations (Wright, 1955, 1956, Wright and 

 Stadtman, 1956). 



Serine synthesis from phosphoglycer ate. Since glycine and serine are both nutritionally 

 non-essential amino acids in animal tissues and many microorganisms, it is neces- 

 sary to inquire next as to the origin of the carbon skeletons of these amino acids. 

 The evidence now indicates that serine can be synthesized prior to glycine in certain 



Literature j>. 124 



