IV NUCLEOTIDE SYNTHESIS 95 



The reverse of the condensation of IMP and aspartate, the condensation of fumaric acid 

 with AMP to form adenylosuccinate, takes place in yeast autolysates. 



The synthesis of guanylic acid (GMP) requires the prior oxidation of IMP to 

 xanthyHc acid (XMP). In this oxidative step it has been shown in experiments 

 with bone marrow (Abrams and Bentley, 1955a, b, c), Aerobacter, and E. coli 

 enzymes (Gehring and Magasanik, 1955) that DPN"^ is necessary. The amina- 

 tion of XMP to GMP has been studied with bone marrow (Abrams and Bentley 

 1955b) and liver enzymes (Lagerkvist, 1955). The amide group of glutamine is 

 the source of the 2-amino grotip of GMP. ATP is required in the conversion. By 

 analogy with the adenylosuccinate intermediate in AMP synthesis, a guanylo- 

 glutaric acid derivative has been suggested as an intermediate in GMP synthesis. 

 In the case of the bacterial enzymes, ammonia is reqtiired instead of gltitamine: 



i) XMP + ATP + NH% -^ GMP + AMP + PP 



An Aerobacter mutant which requires guanine and excretes xanthosine is unable to aminate 

 XMP (reaction i). The conversion of guanine to nucleic acid adenine apparently does 

 not take place by a reversal of these reactions. During the conversion of guanine to adenine 

 in Aerobacter mutants, the amino substituted carbon 2 of guanine is probably transferred 

 to THFA. The products of this reaction are AICAR and NjQ-forniimino-THFx\. The 

 transformylation of AICAR results in the formation of IMP, the AMP precursor (Maga- 

 sanik et al., 1956). 



J. The utilization of free purines 

 [a] Labelled purines 



Experiments with adenine-S-^'^C or adenine-^^N have shown that this sub- 

 stance is rapidly incorporated in vivo into nucleic acid purines of normal tissues 

 and tumors (Furlong ^f a/., 1955; Bennett e/ a/., 1955, 1956; Brown, 1950, 1 951), the 

 ribonucleic acid or acid soluble nucleotide purines of tissue slices or homogenates 

 (Goldwasser, 1953, 1954; Lajtha et al., 1954; Abrams and Goldinger, 1951) and 

 into Lactobacilli and yeast nucleic acids (Abrams, 1952; Bennett and Kruekel, 

 1955; Marrian, 1954). On the other hand, free guanine is rather poorly incorpo- 

 rated into the purines of the mouse, hamster, or rabbit bone marrow cells (Brown, 

 1950, 1 951). Adenine is converted to guanine and guanine to adenine by rabbit 

 bone marrow cells, (Abrams and Goldinger, 1951). Guanine is a very poor nucleic 

 acid precursor in human or rat tumors (Bennett and Skipper, 1955; Bennett et al., 

 1955. 1956)- 



In contrast to the higher animals, Tetrahymena, in which de novo purine synthesis is apparently 

 blocked (Kidder et al., 1950), requires guanine for growth. Adenine or hypoxanthine can 

 spare but not replace the guanine requirements of this organism. 



Hypoxanthine-8-^'*C is a moderately effective prectirsor of the nucleic acid 

 purines of the hamster but not of the rat or mouse (Bennett and Skipper, 1955). 

 Neither hypoxanthine nor xanthine are well utilized by a number of tumor tissues 

 (Bennett et al., 1956) nor is xanthine utilized significantly by normal rat tissues. 



Some free AICA can be utilized as a precursor of nucleic acid purines by animals and 

 microorganisms. It is converted to uric acid by man (Seegmiller et al., 1955) and by 

 pigeons (Miller et al., 1950) and to allantoin, nucleotide purines, and nucleic acid purines 

 in the rat, to nucleotide and nucleic acid adenine in yeast, and tissue nucleic acid purines 

 in mice. Pigeon livers convert AICA to hypoxanthine. 



Literature p. 124 



