108 



THE CELL AND PROTOPLASM 



on micro-organisms. The broadest gen- 

 eralization of the concept that living beings 

 require energy for the maintenance of life 

 as well as for growth would, consequently, 

 find expression in the following statement, 

 which might well be considered one of the 

 basic working hypothesis of the general 

 microbiologists, viz. : 



Any chemical process which, thermo- 

 dynamically , will proceed with the libera- 

 tion of free energy can he used hy some liv- 

 ing organism as the main or even as the sole 

 source for fulfilling its energetic require- 

 ments. 



Whereas the problem of energy require- 

 ments was, from the start, a typical physio- 

 logical one, it soon aroused the interests 

 of the chemist. The conditions under 

 which the various reactions proceeded were 

 entirely different from those under which 

 similar chemical reactions would go on "in 

 vitro," and for some of the processes a clear 

 chemical analogon was entirely unknown. 

 Thus, with a view to studying and estab- 

 lishing the means by which such reactions 

 are accomplished by living organisms, the 

 chemists from Liebig on, influenced par- 

 ticularly by the ideas of von Bayer, Moritz 

 Traube, etc., have explored this field. 



Though almost entirely theoretical in 

 the beginning, these researches have led to 

 an astonishingly rapid progress in our 

 understanding during the past 25 years. 

 And to the microbiologist it is indeed 

 gratifying to realize how important in this 

 development has been the part played by 

 studies on the chemical activities of micro- 

 organisms. 



The first great contribution, the signifi- 

 cance of which can hardly be overestimated, 

 was the concept that biological reactions 

 should be considered as the final outcome 

 of a series of simple step reactions, chemi- 

 cally intelligible and proceeding in strict 

 succession. The concept is easily traceable 

 to von Bayer, but it was not until Carl Neu- 

 berg published his epoch-making studies on 

 alcoholic fermentation, later followed by 

 researches on various bacterial fermenta- 

 tion and oxidation processes, that the gen- 

 eral validity and applicability, as well as 

 the tremendous significance, of this hypoth- 



esis became thoroughly established on the 

 basis of sound and far-reaching experi- 

 mental results (Neuberg and Kobel 1933). 

 Apart from the evidence in support of the 

 concept of successive step-reactions, this 

 work, later greatly extended by the re- 

 searches of Kluyver and his school (Kluy- 

 ver and Donker 1926; Kluyver 1931**), and 

 by Stephenson and her co-workers (1939), 

 has also yielded the important result that 

 in the most diverse processes there is a con- 

 siderable similarity in many of the inter- 

 mediate steps. This is true not only if one 

 and the same substrate is acted upon by 

 different organisms, but also for the de- 

 composition of different groups of sub- 

 strates. 



Among the groups of substrates that 

 have been studied most extensively the 

 carbohydrates undoubtedly rank first. We 

 are now familiar with the notion that in 

 most cases a sugar molecule is attacked 

 first through the formation of phosphate 

 esters of the monosaccharides, which sub- 

 sequently undergo the more or less clearly 

 established cleavage processes. This phos- 

 phorylation, now recognized as of such 

 wide occurrence in plants and animals and 

 of such fundamental importance for sugar 

 metabolism, was discovered nearly 40 years 

 ago by Harden and Young (1932) as a re- 

 sult of their studies on alcoholic fermenta- 

 tion. It is also readily understandable that 

 Meyerhof (1937), one of the ablest investi- 

 gators of the sugar-breakdown processes, 

 has turned on many occasions to the micro- 

 organisms for experimental material. The 

 recent investigations of Stone and Werk- 

 man (1937, 1938) have furnished consider- 

 able support for the view that in bacterial 

 carbohydrate metabolism, which was not 

 studied previously from the angle of phos- 

 phorylations, the same intermediate pro- 

 ducts would also arise. 



Most of the evidence in support of the 

 widespread occurrence of phosphoryla- 

 tions during sugar metabolism has been of 

 a somewhat indirect nature, based upon 

 studies with press juice in the presence of 

 more or less specific poisons which prevent 



G For a complete bibliography (1939) see Chem. 

 Weelchlad, 36: 307-323. 



