Energy Exchange and Enzyme Development During Embryogenesis 545 



(Albaum and Worley, '42). Levy and Young 

 ('48) have contested this, however, and have 

 reported a rise in cytochrome oxidase activity 

 (per miUigram dry weight) from the third 

 to the fifth day of development. It may be 

 noted that Levy and Young did not deter- 

 mine dry weight themselves but related 

 their enzyme data to Murray's figures. 

 Furthermore, they did not determine the 

 developmental age of the embryos used in 

 the enzyme assays but calculated them from 

 measurements of wet weight. Too much 

 emphasis should perhaps not be placed on 

 the absolute values of enzyme activity during 

 the earliest developmental stages when rela- 

 tive errors in enzyme determination and 

 in weight and age can be of considerable 

 magnitude. 



Enzyme Development and Diflferentiation. In 

 the development of the embryo, functional 

 activities are at first of a general and un- 

 specific type and are concerned primarily 

 with such events as maintenance and growth. 

 Later on, however, the so-called special 

 functions of tissues and organs, such as con- 

 traction, conduction, secretion, etc., make 

 their appearance. In general, only after 

 morphological development has proceeded to 

 a definite extent do the special functions 

 come into being. In the case of the nervous 

 system, Harrison ('35) has commented as 

 follows: "The relative size of the nervous 

 system in vertebrate embryos reaches its 

 maximum before nervous function begins. 

 Complicated neuromuscular mechanisms in 

 higher vertebrates are essentially complete 

 structurally before they become active, and 

 in those forms, such as the Amphibia, where 

 activity seems to develop concomitantly with 

 the development of structure, nervous fvmc- 

 tion may be suppressed by chloretone with- 

 out interfering at all with the development 

 of correlated structures or with their normal 

 fvmctioning as soon as the effect of the 

 anaesthetic passes off. The embryo carries 

 on the ordinary functions of organisms, such 

 as respiration and metabolism, but the pecul- 

 iarly developmental processes are apart from 

 or superimposed upon these and are for the 

 most part continuously changing and irre- 

 versible." 



Many of the important reactions which 

 underlie functional activities, both general 

 and special, are catalyzed by enzymes. The 

 immediate change from an inactive state 

 to one of activity may be expected, then, 

 to be concerned primarily with development 

 of biochemical mechanisms, through which 

 physiological activities become possible, 



rather than with marked alterations in the 

 structural elements, through which they are 

 made manifest. This idea has been more 

 fully elaborated by Barron ('41), Herrmann 

 ('53), and Shen ('54). If this argviment is 

 valid, one would expect to find that those 

 enzymes that are uniquely involved in a par- 

 ticular function would be formed, or increase 

 their activity, prior to or synchronously with 

 development of functional capacity. 



The analysis of enzymes in the entire 

 embryo generally provides limited informa- 

 tion on the relation between enzyme changes 

 and functional differentiation of specific 

 structures. But the study of individual organs 

 has furnished a great deal of evidence that 

 development of function and development of 

 enzymes are correlated events. 



Pioneer work along this line was done by 

 Flexner and his co-workers. During differ- 

 entiation of the pig cerebral cortex, two 

 "critical periods" are noted. The first of 

 these occurs about half-way through gesta- 

 tion and is marked by changes in size and 

 shape of neurons and in pattern of Nissl 

 substance. At this time, the cytochrome- 

 cytochrome oxidase system increases in ac- 

 tivity, and this appears as an abrupt change 

 when enzyme activity is plotted against fetal 

 crown-rump length. Tissue respiration re- 

 mains constant, however, as does also the 

 activity of cytochrome oxidase, and Flexner 

 et al. ('41) have concluded that the factor 

 which changes during the first period of 

 differentiation is the concentration of cyto- 

 chrome. During the second critical period, 

 neurons assume their adult characteristics, 

 and, at the same time, respiratory rate, 

 cytochrome oxidase, and succinic dehydro- 

 genase activities begin to rise to their adult 

 levels (Flexner and Flexner, '46). A similar 

 rise in succinoxidase activity was found in 

 the developing rat brain by Potter, Schnei- 

 der, and Liebl ('45), but owing to the 

 greater immaturity of the rat at birth, the 

 increase does not commence imtil the fifth 

 to seventh day post partum. 



Since respiratory enzymes are ubiquitous 

 and are concerned with the ordinary ac- 

 tivities of all cells, it might be expected that 

 enzymes more intimately connected with 

 specific functions would show more marked 

 correlations with functional development.* 



* Perhaps the most striking example of sudden 

 enzyme development is that of xanthine oxidase 

 in the chick embryo. Morgan ('30) has reported 

 that the enzyme is present in the liver of a chick 

 that has just made a hole in the shell; it is absent 

 in the liver of a chick that has not yet made a hole. 



