Cellular Metabolism 



77 



metabolized rapidly. Presumably, the added 

 pyruvate enters the system and, in effect, 

 blocks the utilization of endogenous sub- 

 strates. 



Partly because relatively few coenzyme 

 systems are essential to many different reac- 

 tions, the metabolism of the cell represents 

 a closely integrated system in which inter- 

 ference with one chemical step may have 

 profound results on some remote part of the 

 living system. The coenzyme systems repre- 

 sent not only important energy pools for the 

 coupling of a variety of reactions, bvit also 

 coordinating mechanisms. 



ENERGY-UTILIZING SYSTEMS 



The burning of food results, in the cell, 

 in the formation of low-energy* waste prod- 

 ucts from high energy precursors. In analogy 

 with the more obvious engines of industry, 

 the living machines must have mechanisms 

 for converting the energy of burning to use- 

 ful functions, imless the whole process is to 

 result in waste heat. To use terms common 

 in physics, cells must have transducer mech- 

 anisms. There are no apparent structures 

 in cells that could function as heat expan- 

 sion engines. It is possible that electrical 

 work may be done and keyed directly to 

 metabolism through the existence of oriented 

 electron transfer systems, e.g., Fe-oxidases 

 oriented at surfaces (cf. Lundegardh, '45), 

 but this has yet to be demonstrated. The 

 only method by which oxidative energy is 

 known to be made use of in quantitatively 

 important amounts is by the transfer of 

 chemical energy directly to other reactions or 

 to devices for producing movements of fluids 

 and cells. 



SYNTHESIS 



In order for the energy of one reaction, 

 e.g., a step in the oxidative cycle, to be used 

 for driving a synthetic reaction, the two 

 must have a common reactant (cf. Johnson, 

 in Lardy, '50). Presumably a common reac- 

 tant could take a variety of forms. It is a 

 matter of considerable interest that relatively 

 few such common reactants are known. The 

 best imderstood, which are implicated in 

 many cellular functions, are the members 



* For obvious reasons the details of the energetics 

 of metabolism cannot be given here and the term 

 "energy" must be used rather loosely. The reader 

 is referred to Clark ('49) or to the chapter by John- 

 son in Lardy ('50) for further definitions of the 

 terms used. 



of the phosphorylation coenzyme system, 

 ADP and ATP. 



Lipmann ('41) has discussed in a very 

 readable fashion the formation of energy- 

 rich phosphate bonds. In general the proc- 

 ess may be illustrated by the oxidation of 

 an aldehyde (such as the glyceraldehyde 

 of Fig. 3) to an acid (glyceric). In the test 

 tube, in the presence of water, this presum- 

 ably takes place with the formation of an 

 unstable hydrate and the subequent removal 

 of hydrogen to give the terminal carboxyl 

 group instead of the aldehyde. This process 

 is essentially irreversible and the energy 

 yielded is lost as heat. In the presence of 

 orthophosphate, however, water is replaced 

 by phosphoric acid and the oxidation then 

 yields an acid anhydride. The link between 

 the phosphoric acid and the organic acid is 

 called the energy-rich phosphate bond. Lip- 

 mann ('41) may be consulted for the further 

 specification of energy-rich linkages. 



The oxidation of the aldehyde in the pres- 

 ence of phosphate results in a loss of heat per 

 unit of hydrogen transferred less than that 

 during oxidation following hydration, and 

 the reaction is reversible. Of greatest im- 

 portance to the present discussion is the fact 

 that two groups, phosphate and organic acid, 

 have been linked together, a synthesis has 

 taken place, and the groups so attached can 

 now be shifted around by a variety of en- 

 zymes in cells. Especially, the labile phos- 

 phate can be shifted by transphosphoryla- 

 tion to such phosphate acceptors as creatine, 

 arginine and the adenylic acid system with 

 the retention of the "high-energy" character- 

 istics, or from the adenylic acid system to 

 sugars or other forms to give ordinary ester 

 linkages. 



The formation of the bonds between phos- 

 phate and other groups has acquired height- 

 ened interest from the finding that the group 

 that attaches to the phosphate becomes it- 

 self transferable in most cases, and thus 

 synthesis of different complex organic com- 

 pounds becomes at least theoretically pos- 

 sible. This sequence of events is illustrated 

 by outlining the synthesis of sucrose from 

 glucose and fructose (Hassid and Doudoroff, 

 '50). The over-all reaction is glucose -f fruc- 

 tose ;=i sucrose. The reaction was first known 

 as it occurred in ordinary hydrolysis where 

 the reaction went far to the side of the split 

 products. For many years, under the spell 

 of the idea of reversibility of hydrolytic en- 

 zyme action, biochemists thought that sucrose 

 synthesis, which takes place ranidly in plants, 

 was caused by sucrase acting in some special 



