IV BIOSYNTHESIS OF AMINO ACIDS 65 



geot, 1 953- 1 954; Singer and Kearney, 1956). The cysteine sulfinic acid trans- 

 aminates with a-ketoglutaric acid to form glutamic acid and ^-sulfinylpyruvic acid. 

 A cysteine sulfinic acid transamination reaction with a-ketoglutarate has also been 

 observed in brain tissue. Cysteine sulfinic acid is readily desulfinated to sulfite and 

 to pyruvate. Presumably, ^-sulfinylpyruvate is an intermediate in sulfite formation. 

 The sulfite may then be further oxidized to sulfate. The pyruvate formed above 

 reacts with the glutamic acid to regenerate the a-ketoglutarate while alanine 

 accumulates under the experimental conditions used. In mammalian tissues, 

 cysteine sulfinic acid may also be decarboxylated and oxidized to hypotaurine 

 and to taurine. 



(d) Phenylalanine, tyrosine and tryptophane {Fig. 22) 



The benzene rings of phenylalanine, tyrosine, and tryptophane are derived 

 from a series of precursors whose recognition was made possible by the isolation 

 of a number of "aromatic polyauxotrophs" of E. coli, Aerobacter aerogenes and 

 Neurospora (Davis, 1955a, b). These mutants required the three aromatic amino 

 acids for growth and in addition most of them required traces of three other 

 benzenoid compovmds : /j-aminobenzoic acid, j^-hydroxybenzoic acid, and an un- 

 known sixth compound. Shikimic acid, a substance previously found in plants, 

 substituted for all of the above factors (Davis, 1951). Another group of £■. coli 

 mutants, blocked at later stages in aromatic synthesis, accumulated shikimic 

 acid in the culture filtrates. These results suggested that shikimic acid was a 

 common precursor of the aromatic metabolites. 



By similar observations, dehydroshikimic acid and dehydroquinic acid were 

 shown to be on the same metabolic sequence prior to shikimic acid. E. coli strains 

 blocked immediately before shikimic acid accumulated dehydroshikimic acid. 

 A Neurospora mutant (Y 7655a), on the other hand, accumulated some dehydro- 

 shikimic acid but mostly protocatechuic acid (3, 4-dihydroxybenzoic acid; Tatum 

 and Gross, 1956). Further support for the shikimate pathway was obtained by the 

 demonstration of an enzyme in E. coli extracts which dehydrated 5-dehydroquinic 

 acid to 5-dehydroshikimic acid (Mitsuhashi and Davis, 1954a). A second enzyme 

 found in E. coli, plants, yeast, and Aerobacter cells, catalyzed the reduction of dehy- 

 droshikimic to shikimic acid (Mitsuhashi and Davis, 1954b; Yaniv and Gilvarg, 

 1955). This enzyme was absent from those E. coli mutants which were blocked 

 between dehydroshikimic and shikimic acid. Reduced TPN^ was a cofactor for 

 the reaction. 



Certain mutants which accumulated shikimic acid, also accumulated 

 5-phosphoshikimate and an unknown compound, Zj, (Weiss and Mingioli, 1956). 

 The unknown compound, Zj, is apparently a conjugate of shikimate with pyruvate. 

 Extracts of a mutant blocked after (Zj) synthesize this substance (ZJ from phos- 

 phoshikimate and phosphoenol pyruvate, but not from shikimate. Phospho- 

 shikimate therefore appears to be an intermediate between shikimate and com- 

 pound Zj. 



Knowledge as to the origin of shikimic acid was derived from enzymatic and isotope 

 studies. E. coli mutants which accumulated shikimic acid were grown in the presence of 

 radioactive glucose. The distribution of radioactivity in the carbons of shikimic acid 



Literature p. 124 



