CHEMICAL ARCHITECTURE OF THE CENTRAL NERVOUS SYSTEM 



1809 



(1, 87, 1 13, 157), and recent studies by Waelsch and 

 co-workers have provided direct confirmation by 

 demonstrating very active incorporation of amino 

 acids into proteins by brain microsomes (43, 82, 

 245). These findings have been nicely complemented 

 by the histochemical demonstration of the presence 

 of and synthesis of a protein enzyme, acetylcholin- 

 esterase, in the endoplasmic reticulum (microsomal 

 fraction, Nissl substance) of neurons (81, 224). 



This brief survey has been intended to indicate 

 the principal features of cellular organization, since 

 the details of metabolism are covered in succeeding 

 chapters. It is apparent that the various cell elements 

 are not completely independent entities from a 

 functional standpoint. As Hogeboom et al. (109) 

 put it, the cell is not simply a haphazard bag of 

 enzymes nor is it biochemically just a nucleus or 

 collection of mitochondria, but it is a complicated 

 mosaic of structural units endowed witli specific 

 chemical properties and, although some functional 

 autonomy is suggested, in no instance does this 

 appear to be complete since the structural units 

 appear to be mutually dependant on one another for 

 their contributions to the metabolism of the cell. 



These views have been amply substantiated by the 

 growing recognition of factors which arc important 

 in the regulation of cellular metabolism (250). Two 

 of these factors are pertinent to this discussion. 

 Brady (26) has pointed out that the synthesis of 

 fatty acids, cholesterol and sphingosine require, as 

 cofactor, reduced triphosphopyridine nucleotide 

 (TPNH) and that the principal source of TPNII is 

 from the oxidation of glucose via the hexose mono- 

 phosphate (HMP) shunt pathway. In contrast to 

 neonatal brain where synthesis of these lipid com- 

 ponents is active, adult brain exhibits relatively little 

 turnover of these constituents. The metabolic path- 

 ways originally devoted primarily to active synthesis 

 are in the mature nervous system shifted to sustaining 

 reactions, and there is little metabolism via the 

 HMP shunt pathway and hence little TPNH avail- 

 able. Yet the enzymes of the HMP shunt pathwav are 

 still readily demonstrable in adult brain tissue, 

 expecially in myelinated areas. Brady (26) concludes 

 that it is not the lack of enzymes which has caused 

 this shift in metabolic emphasis but some other 

 regulatory mechanism such as suppression of these 

 synthetic pathways by accumulation of biosynthetic 

 end products. 



A second and possibly not unrelated factor is that 

 of compartmentation. Some 50 years ago Hofmeister 

 (107) suggested that the enzymes necessary for the 



synthesis and for the breakdown (utilization) of 

 glycogen must be separated within the cell or net 

 storage of glycogen would be unlikely to occur. With 

 the advent of isotopic tracer techniques for studying 

 cellular metabolism, evidence for compartmentation 

 phenomena has become increasingly common (250). 

 There are now at least three examples of cellular 

 metabolic compartmentation in the central nervous 

 system: phosphorylation of hexoses (239), synthesis 

 of glutamine (245) and synthesis of 7-aminobutyric 

 acid (McKhann, Albers & Tower, unpublished 

 observations). Undoubtedly there will be many more. 

 Anatomists and physiologists have dealt with com- 

 partmentation at tissue and cell levels for many 

 years; now the biochemist must also deal with it in 

 intracellular terms. It is obvious that the segregation 

 of substrates, cofactors and enzymes within the cell 

 imposes regulatory actions upon processes in one 

 compartment which depend upon metabolic activity 

 in another. In addition the interaction of processes in 

 various compartments poses problems in terms of 

 transport among them and proper distribution of 

 necessary substrates, cofactors and products. Com- 

 partmentation is of great importance at the metabolic 

 level but it also must have fundamental significance 

 lor the functional activity of the cell as a whole. A 

 recenl review by Waelsch (245) considers these 

 points as they may apply to the central nervous 

 system. 



From the foregoing data some idea of the kind of 

 cellular organization to be expected in cells of the 

 central nervous system, both in terms of structure and 

 function, can be obtained. It is difficult to evaluate 

 how representative the data are for neurons. The 

 analyses of fractions of gray and of white matter by 

 Aliood et al. (3) and by Korey & Orchen (135) are 

 the only ones reported, and their results are similar 

 to those of Heller & Elliott (100) in that enzyme 

 activities of white matter fractions are much less 

 than those of gray. However, the pattern of distri- 

 bution among the fractions is essentially similar in 

 both types of tissue. It seems likely that the neuron 

 will prove to have a cellular, chemical organization 

 which resembles essentially that outlined in table 6. 

 As Hogeboom et al. (109) and Waelsch (245) suggest, 

 these data would seem to bear on that aspect of 

 differentiation involving strategic intracellular loca- 

 tion of the several specifically endowed elements, 

 so that their individual activities could be efficiently 

 integrated in the overall function of the cell and 

 tissue. It is pertinent to recall that, by electron 



