animal collagenase and collagen metabolism 687 



Discussion 



The accretion or diminution of structural elements such as colla- 

 gen is probal)ly accomplished by altering the balance between rates 

 of synthesis and rates of degradation. The manner in which this 

 might occur is not yet known. The present studies suggest that 

 where rapid collagen removal occurs, as in the resorbing tadpole 

 tail, there is an increase in degradative activity. Synthetic activity 

 seems to remain constant. 



It is of interest that there is substantial collagenolytic activity in 

 cultures of nonmetamorphosing tadpole tissues but such activity is 

 essentially nondetectable in fresh tissue extracts. It may be that the 

 culture technique allows the tissue to reveal its full potential, which 

 it cannot do under in vivo restraints. Such hypothetical inhibitors 

 were not found when large amounts of tadpole tissue extracts were 

 added to the culture medium to prevent the appearance of colla- 

 genase. Earlier experiments (Gross and Lapiere, 1962) indicate that 

 there is no storage of the active enzyme in the tissues, but that its 

 accumulation in culture is a result of new synthesis or activation of 

 a zymogen molecule. The possibility of induction or inhibition by 

 substrate or its breakdown products requires further inquiry. 



The increase in collagenolytic activity in cultures of metamorphos- 

 ing tail fin ranged from two- to fourfold in repeated experiments. 

 This increment might be largely ascribed to an increased con- 

 centration of enzyme-producing cells rather than to increased syn- 

 thesis per cell. The concentration effect might result from the loss 

 in tissue water. We propose that collagen resorption increases in 

 metamoi-phosis because the cells making collagenase carry the en- 

 zyme to the substrate when they invade the collagenous basement 

 lamella. 



We hypothesize from these metabolic studies that the old insoluble 

 collagen framework is preferentially removed and replaced continu- 

 ously by a new insoluble scaffolding. It is possible that either specific 

 cells responsible for removal can select out the older fibrils or the 

 newly deposited fibrils are protected in some manner from attack by 

 these cells. The ground substance, which presumably is produced 



