BIOSYNTHESIS OF PROTEIN 643 

ASP —> Asp-p* —> HS > HSP -> threonine —> a-keto butyric —> isoleucine 
x 
HC 
NX 
methionine 
One interpretation of the system pictures the amino acid site as a separate, linked 
enzymatic system schematically indicated in Fig. 7. To account for the experimental 
observations no branched reactions as shown in the aspartic pathway above may 
exist. Once aspartic acid has entered the IsoL system its final destination must be 
isoleucine, and no¢ methionine (or even threonine). An independent linked enzymatic 
system is required for the conversion of aspartic acid to each of the above amino 
acids. If this were not the case it would be possible to saturate the ASP sites shown 
in Fig. 6 with high concentrations of exogenous methionine and exclude any endo- 



Exogenous ASP-=ASP-P--HS—=HS-P-=THREO-=«-KETO BUTYRIC-=ISOLEUCINE-= 

Isoleucine 
Threonine 
ASP-ASP-P-=HS-=HS-P-=THREONINE —= 
ASP-=ASPARTIC ACID—= 
Endogenous ASP-~ASP-P-—HS=H C-=ME THIONINE—= 
Aspartic acid 
Fig. 7. Linked-enzyme system model. 
genously formed aspartic acid from entering the system. Further evidence supporting 
the concept of separate linked biosynthetic enzymatic systems has been recently 
shown by STADTMAN ef al. with their observation that in F. coli a different aspar- 
tokinase molecule is involved in the conversion of aspartic acid to threonine from 
that found in the biosynthesis of lysine from aspartic acid’. 
As in the site model, entry into the linked-enzyme system must occur at the first 
step of the synthetic events. The IsoLt system will accept isoleucine and any pre- 
cursor or intermediate of isoleucine but the ultimate product will be only isoleucine. 
Entry along any part of the conversion sequence would result in competitive effects, 
effects not detected in the conversion of internal-pool |C)aspartic acid to protein iso- 
leucine. 
Control of biosynthetic reactions 
At least three kinds of mechanisms have been postulated which account for the 
preferential utilization of exogenous metabolites by microorganisms!®: (1) simple 
mass-law equilibria along the biosynthetic chain; (2) cessation of synthesis of at 
* Abbreviations: ASP-P: aspartyl-phosphate; HS: homoserine; HSP: homoserinephos- 
phate; HC: homocysteine. 
References p. 645 
