588 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



rather than a simple inhibition of the biosynthetic pathway. It is possible 

 to go back farther and inhibit the synthesis of pantothenate by analogs of 

 pantoate or /5-alanine. For example, 2,3-dichloroisobutyrate blocks the cou- 

 pling of these two components of pantothenate, competitive with pantoate 

 and uncompetitive with /5-alanine (K^ = 1.4-6.4 mM) (Hilton, 1958). 



Biotin functions in several metabolic pathways (synthesis of aspartate 

 and higher fatty acids, and COg fixation) and in certain organisms can be 

 formed from desthiobiotin. 2-Oxo-4-imidazolidinecaproate (desmethyldes- 

 thiobiotin) inhibits the growth of E. coli by competing with desthiobiotin 

 for an enzyme involved in biotin synthesis, and this inhibition is competi- 

 tive (Rogers and Shive, 1947). Biotin by an unknown mechanism stimulates 

 fermentation in biotin-deficient yeast and this is inhibited by homooxy- 

 biotin, oxybiotinsulfonate (COO- group replaced by SOg" group in oxybio- 

 tin), and 7-(3,4-ureylenecyclohexyl)butyrate when the analogs are added 



n O 



HN" 



■NH 



HN' 



■^NH 



Biotin 



■(CH2)^COO" 



H3C CH.— (CH2)4— COO 

 Desthiobiotin 



O 



II 



c 





CH.r-(CH2) — COO' 



-(CH2)5— COO' 



Desmethyldes- 

 thiobiotin 



Homobiotin 



HN"^ NH 



HN^ NH 



(CH,) — COO' 



/ V(CH2)3— COO' 



Oxybiotin 



y-(3, 4-Ureylenecyclo- 

 hexyl)butyrate 



