V METABOLIC CHANGES 6ll 



ber of components show two cycles of change (Table 8) and the present picture is 

 probably an oversimplification. Nevertheless recent evidence seems to strengthen 

 the general validity of the simple oscillation. 



It now seems more certain (Fodor et al., 1955) that acid phosphatase is active 

 in regressive processes. Of much wider significance is the demonstration by De 

 Duve^/«/. (1955) that the enzyme is located on cytoplasmic particles, possibly the 

 same particles ("lysosomes") as those containing cathepsins, deoxyribonuclease, 

 ribonuclease, [^-glucuronidase and other lytic enzymes. The lysosomes in fact 

 may be complete batteries of R-phase enzymes, held inactive in normal healthy 

 cells. [3-Glucuronidase, one of the enzymes concerned in the breakdown of the mu- 

 copolysaccharides of the skeletal and connective tissues, is a recent addition to 

 the enzymes known to become more active in the R-phase (Hollinger and Rossi- 

 ter, 1952; Mills et al., 1953). 



(fl) Protein metabolism 



There is an initial decrease in total nitrogen of regenerating liver (Price and 

 Laird, 1950; Harkness, 1952) and in concentration of protein (Paul et al., 1945) 

 from a normal 25.5^/0 of the wet-weight to 12.5% on the third day. In regener- 

 ating skin it decreases from 41.5 mg/g wet weight to 19.0 mg (Williamson and 

 Fromm, 1955). These decreases in protein-concentration, in fact, seem largely 

 attributable to the increase in water-content (Paul et al., 1945) but in sectioned 

 nerves a genuine decrease in protein seems probable (see Caspersson, 1950, p. 130). 

 Free amino acids and other breakdown-products of proteins accumulate locally 

 (Orechovitch and Bromley, 1934), including those from mucoproteins (Sylven, 

 1941 ; Balazs and Holmgren, 1950) and the accumulation persists (Vladimirova, 

 19355 Williamson and Fromm, 1955) presumably for re-use. In the regenerating 

 liver most of the (protein) enzymes decrease in amount (Novikoff and Potter, 

 1948; Rosenthal et al., 1951). Proteolytic enzymes become more active, particu- 

 larly 'cathepsins' intracellular proteases with a pH-optimum at 4.7 (Orechovitch, 

 1934; Orechovitch et al., 1935; Striganova, 1940; Ma.ver et al., ig^2; Jensen et al., 

 1956). The regenerative power of tissues is proportional to their intrinsic proteolytic 

 (autolytic) activity (Sokolova, 1 942) . The blood leaving an injured region also shows 

 increased peptidase activity (Selye, 1948). At the acid pH prevailing, cathepsins 

 will digest even collagen (Sherry et al., 1954). Osteoclasts, (perhaps), and other 

 cells (Menkin, 1950), secrete proteases at this time. It is significant that cells 

 transferred to culture-media also at first show increased proteolytic activity 

 (Willmer, 1942a) and other R-phase activities. Regressing cancerous growths also 

 show increased proteolysis (Maver et al., 1948; Fodor et al., 1955). By contrast the 

 tissues of embryos, which are probably in the P-phase throughout, never show high 

 catheptic activity (Borger and Peters, 1933). 



At first more sensitive (Orechovitch and Sokolova, 1940), regenerating tissues 

 become less sensitive to catheptic digestion than normal dviring the P-phase 

 (Orechovitch and Bromley, 1934), since grafts of normal skin over the blastema 

 are then digested. In consequence, perhaps, the young blastema is able to ensure 

 adequate regression of tissues of the stump. On the other hand this production of 

 proteases in the blastema may be associated with the converse activity of protein 



Literature p. 64g 



