Topographical Aspects of Metabolic Regulations! 



preconceived ideas of cellular organization play a not insigni- 

 ficant part. 



A direct consequence of the segregation of enzymes is that 

 media of different composition tend to form on each side of 

 the membranes separating distinct enzyme systems. Thus, 

 enzymic heterogeneity itself becomes responsible for the 

 unequal distribution of numerous other cell constituents and 

 for the appearance of diffusion gradients, membrane potentials 

 and other manifestations of heterogeneity at the various 

 interfaces. The exchanges governed by these phenomena 

 may be of paramount importance in the regulation of cell 

 metabolism. 



A higher level of organization is reached if the catalysts 

 which are part of a given unit are themselves associated 

 structurally in a manner which either increases their efficiency 

 as a system or provides the system with special properties. 

 That such organized chains of enzymes may be present in the 

 insoluble framework of the cell now appears fairly probable 

 and it has even been maintained that soluble catalysts may 

 be grouped in labile polyenzymic functional units in the intact 

 cell. 



Finally, one should not forget that the structural com-, 

 ponents of cells are themselves in a dynamic state. We are 

 at present almost entirely ignorant of the mechanisms 

 whereby intracellular units such as mitochondria are renewed 

 or multiplied. This is obviously a problem of primary 

 importance. 



Investigations from our laboratory on the intracellular 

 location of hydrolases may serve to illustrate the main 

 physiological aspects of enzyme segregation. This work, 

 which has recently been reviewed in detail (de Duve, 1959), 

 has led to the identification in liver and several other tissues 

 of a distinct group of cytoplasmic particles, termed "lysosomes " 

 and containing a number of soluble acid hydrolases with an 

 acid pH optimum. These enzymes include a phosphatase, a 

 ribonuclease, a deoxyribonuclease, a cathepsin, a p-glucuro- 

 nidase and an aryl-sulphatase and, therefore, have a combined 



