ii8 



INTERMEDIARY METABOLISM AND GROWTH 



HO- 



OH 



TPNH2 



HoO 



HO 



Dihydrouracil 



HN 



o=c 



COOH 

 CH2 

 -CHo 



HoO 



/3-Ureidopropionate 



Fig. 56. Conversion of uracil to ^-alanine. 



NH3+ CO2 

 + 

 COOH 

 CH2 



CH2 



I 



NH2 



j3-Alanine 



(b) Source of ^-alanine 



Two sources are now known for the ^-alanine. 



a) ^-alanine may be formed in certain bacteria by the a-decarboxylation of 

 aspartate (David and Lichstein, 1950): 



Aspartic -^ ^-alanine + CO2 



b) Evidence for the formation of beta alanine from uracil has been obtained in 

 microorganisms, the intact rat, in rat Kver slices, and extracts of rat liver (Fink 

 et al., 1953, 1956; Fink, 1956; Canellakis, 1956a, b; Fig. 56). The degradation of 

 thymine takes place by an analogous mechanism. 



Thymine — > dihydrothymine -^ p-ureidoisobutyric -^ P-aminoisobutyric + NH3 + CO2 



(c) Formation of coenzyme A from pantothenate. 



All of the enzymes required for the synthesis of coenzyme A from pantothenate 

 have been demonstrated in pigeon liver extracts (Hoagland and Novelli, 1954; 

 Reactions 1-5) : 



1 ) Pantothenate + cysteine + ATP > pantothenyl cysteine 



2) Pantothenyl cysteine * pantetheine + CO2 



Mg- 



3) Pantetheine + ATP — -^ 4-phosphopantetheine + ADP 



Mg- 



4) 4-Phosphopantetheine + ATP > dephospho-CoA + PP 



dephospho 



5) Dephospho-CoA + ATP > Coenzyme-A + ADP 



CoA-kinase 



In the liver enzyme system, pantothenylcysteine can replace ATP, pantothenate, 

 and cysteine in the formation of pantetheine, ^-mercaptylethylamine cannot 

 substitute for cysteine in reaction i). The decarboxylation of pantothenylcysteine 

 has also been demonstrated in Acetobacter suboxydans (Brown and Snell, 1953; 

 Levintow and Novelli, 1954). The structure of coenzyme A is shown in Fig. 57. 

 The sulfhydryl group of the [i-mercaptylethylamine portion of the molecule is the 

 active group in coenzyme A function. Acyl-GoA derivatives are important inter- 

 mediates in fatty acid synthesis and oxidation, cholesterol synthesis, citrate synthesis, 

 and the synthesis of N-acetyl-amino compounds (Novelli, 1953). 



