LYSOSOMliS, A NEW GROUP Ol- CVTOPLASMU: PAKTICLliS I29 



on the assumption of a spherical shape, to a nican diaineter ol 0.4 micron and 

 an average density of 1.15, both properties showing a fairly wide dispersion 

 around these mean values; 2) an enzymic equipment lacking several key en- 

 zymes of oxidative metabolism, but comprising a number ol easily soluble hydro- 

 lases (hence the name lysosomes) having further in common an acid pH 

 optimum; ^) a surrounding membrane of lipoprotein nature which effectively 

 prevents the enzymes from escaping from, as well as their respective substrates 

 from penetrating into, the particles; 4) the simultaneous release of all internal 

 enzymes in soluble and fully active form, following injuries to the membrane, as 

 caused by the various treatments listed in the diagram. 



As represented in figure i, our picture of lysosomes is bound to be incomplete. 

 Moreover, it is partly interpretative with regard to the experimental facts on which 

 it rests, stripping the latter of various complicating artifacts to the extent perhaps 

 of oversimplifying reality. Although lengthily discussed in our original publica- 

 tions, these points are not always clearly appreciated and will be briefly examined 

 again here. 



Structure-linked Latency and Activation of Lysosomal Enzymes. First ob- 

 served with acid phosphatase, latency and release were studied in great detail 

 in the case of this enzyme and adequate evidence was, we believe, brought 

 forward in support of the concept that the sole factor involved in these phe- 

 nomena is the integrity of a membrane-like barrier, as depicted in figure i (26, 

 14, 13, 2). Extending the concept to the other enzymes which were found to 

 exhibit similar properties was admittedly an extrapolation, since elaborate proof 

 of the membrane hypothesis was neither provided nor looked for in their case. 

 It could however be shown that the graded release of these enzymes, as produced 

 by several different means, occurred in an almost perfectly parallel fashion with 

 that of acid phosphatase (27, 38, 29, loi) and this was further confirmed when 

 other means of releasing the lysosomal enzymes were uncovered (103, 5). Obvi- 

 ously, the more numerous the enzymes which are released simultaneously, as well 

 as the means which bring about this release, the greater the probability that the 

 linkage which maintains the enzymes in bound and inactive form is an unspecific 

 one. 



Proof that the membrane is of lipoprotein composition was given by the nature 

 of several of the releasing agents, in particular of the enzymic ones (62, 5). We 

 have been unable to confirm the claim of Allard, de Lamirande and Cantero (i) 

 that ribonuclease can cause the release of acid phosphatase; lysozyme also proved 

 inactive in our hands. 



In figure i, the enzymes present within intact particles have been represented 

 as being entirely inactive on external substrates. This has clearly been shown to be 

 the case for acid phosphatase at pH 5, but may not be strictly true at higher pH 

 values, where evidence of a slight penetration of the substrate has been obtained 



