Ill ATP AND RELATED NUCLEOTIDES 47 



6) Enzyme + ATP -^ enzyme-P + ADP 



7) Enzyme-P + glutamyl cysteine -^ enzyme-glutamyl cysteine + Pi 



8) Enzyme-glutamyl cysteine + glycine -> glutathione + enzyme 



The glutathione synthesizing enzyme fails to catalyze any significant exchange 

 of phosphate residues between orthophosphate and ATP unless glutamyl cysteine 

 is present. This exchange is slightly decreased by glycine. No experiments on the 

 exchange of AD^^p ^i^j^ ATP have been performed as yet with the latter 

 enzyme. It is therefore possible that an adenosine diphosphate glutamylcysteine 

 compound may be an intermediate in the reaction instead of the enzyme-phos- 

 phate compound. Glutamic and aspartic acid derivatives of ADP have been re- 

 ported in extracts of chick liver and mammary tissue (Hansen and Hageman, 

 1956). 



IV. THE SYNTHESIS OF PROTOPLASMIC BUILDING BLOCKS 



A. Pentose Formation 



I. Hexose monophosphate shunt 



The pentose sugars, ribose and deoxyribose, are required for the biosynthesis of 

 RNA, DNA, and various coenzymes and nucleotides. Although an enzyme which 

 phosphorylates free ribose and deoxyribose has been described in calf liver 

 (Agranoff et al., 1954) free pentose is rather poorly utihzed by mammalian 

 tissues. Certain microorganisms are, however, capable of fermenting pentose 

 compounds, particularly after periods of adaptation (Stumpf and Horecker, 1956). 

 It seems likely, that most organisms synthesize their pentose requirements from 

 glucose when an adequate supply of the latter compound is available. 



Two mechanisms are known which can account for a net synthesis of ribose 

 from glucose. The first of these, the direct oxidative pathway of glucose metabolism 

 has already been referred to (see p. 3). As a result of the direct oxidative path- 

 way, one mole of glucose is converted to one mole of pentose and one mole of CO,. 

 The dehydrogenase enzymes of the hexose monophosphate shunt have been observ- 

 ed in plants, yeast, bacteria (Lanning and Cohen, 1954; Hauge et al., 1955) fungi 

 (Newburgh et al., 1955) aphids (Newburgh and Cheldelin, 1955) animal tissues 

 and tumors (Racker, 1954; Clock and McLean, 1954; Williams-Ashman, 1953; 

 Villavicencio and Guzman-Barron, 1955). Rather high levels of the dehydrogenase 

 enzymes are found in adrenal cortical tissues (Kelly et al., 1955) and in lymphatic 

 tissues (Clock and McLean, 1954), while the enzyme content of skeletal or car- 

 diac muscle is very low. The levels of both dehydrogenases increase rapidly in 

 lactating mammary tissue from the end of pregnancy to the end of lactation and 

 then fall to very low levels in the involuting mammary gland (Clock and McLean, 

 1953). The dehydrogenases are markedly reduced in livers of diabetic or fasting 

 animals but increased in the livers of thyroxine treated rats (Clock and McLean, 

 1956; Clock et al., 1956b). Clucose-6-phosphatase activity is also increased in the 

 livers of diabetic or thyroxine treated rats. 



Literature p. 124 



