IV 



BIOSYNTHESIS OF AMINO ACIDS 



69 



valeric acid were supplied. A nutritionally similar double auxolroph o£ E. coli ac- 

 cumulated the keto analogs of valine and isoleucine (Umbargerand Magasanik, 

 1951; Umbargerand Mueller, 1951; Adelberg ^^ al., 1955). On the other hand, 

 Neurospora mutants which were blocked earlier in the valine and isoleucine bio- 

 synthetic pathway, were able to utilize the dihydroxy analogs of valine and isoleucine 

 for growth. 



The origin of the keto- and the dihydroxyanalogs was clarified by isotope ex- 

 periments. Fig. 28 depicts the mechanism for valine biosynthesis thereby deduced 



(3)CH3 

 (2) CO 

 (l)COOH 



+ 



CH3 (3) 



CH0(2) 



Pyruvate Acetaldehyde 



(3,3') 

 (2) 

 (2) 

 (1) 



CH3 CH, 



\V 

 CH 



CH-NHa 



COOH 



Valine 



CH3 

 HO-C-C-CH, 



COOH 

 a-Acetolcctate 



CH3 CH, 

 \V 

 CH 



I 



c=o " 



CH3 CH3 



C-OH 



I 



c=o 



COOH. 

 + 2H 



(3,3') 

 (2) 



(2) 



(1) 



glutamic 



.-H2O 



COOH 

 (KV) 



Ketovaline 



CH3 CH3 

 C-OH 



" HCOH 



COOH 



(DHV) 



a,;3-Dihydroxyisovalerate 



CH3 



^CH-CH-CHj-COOH 

 CH3 OH 



CH3-COOH 



■HoO 



(CH3)2-CH-CH=CH-COOH 



-H,0 



(CH3)2-CH-CH2-CH-COOH 

 _ ' I ' I 



i OH 



CH3 

 /CH-CH2-CH-COOH 



CH3 , (JjHj 

 Leucine 



Fig. 28. Biosynthesis of valine and leucine. 



by Weinhouse and coworkers (Strassman et al., 1953). A somewhat similar mech- 

 anism was proposed independently by Adelberg (1954). 



It will be observed that a ketol condensation of acetaldehyde with pyruvate to 

 acetolactate is proposed. The latter substance then undergoes a pinacol rear- 

 rangement to an intermediate which may be reduced to the dihydroxy analogue of 

 valine. Upon dehydration, a-ketoisovalerate is formed and the valine is synthesized 

 from the latter by transamination. The following evidence from isotope experiments 

 performed with yeast and with Aerobacter cells is consistent with the mechanism: 



Literature p. 124 



