6l2 REGENERATION AND GROWTH 7 



synthesis (Urbani, 1955). As in normal growth, there is no evidence of enzymes 

 specific to the direction of synthesis. Pentose nucleic acid, PNA, appears to be 

 concerned with the action of cathepsins in both directions (Maver et al., 1952; 

 Zacchei, 1954). PNA is the major component of dipeptidases (Binkley, 1952) 

 which also are very active during regeneration (Orechovitch, 1936; Urbani, 1955), 

 and again probably in both phases. The pH-optimum for dipeptidases is between 

 7.4 and 7.9 so that they are probably more important in the P-phase than in the 

 earlier, acid phase, but there is evidence also of earlier activity, during proteolysis 

 (Duspiva, 1942; Belfer et al., 1943; Zacchei, 1954; Fleisher, 1955). Dipeptidases 

 can catalyse only the last stages of proteolysis and the first stages of synthesis, so 

 that in the embryo they are active earlier than synthesizing proteases (Urbani, 

 1955). The cathepsin-bearing lysosomes, intermediate in size between the catabo- 

 lising mitochondria and the smaller, synthesizing "microsomes", thus may be 

 active in both catabolism and anabolism. 



The use of amino acids for synthesis of proteins in regeneration has been ade- 

 quately demonstrated. Their rate of turnover in regenerating skin is three to five 

 times that in normal skin (Van Middlesworth, 1953) and amino acids of the food 

 rapidly accumulate in the regeneration blastemata and in the buds of Obelia 

 (Hammett and Chapman, 1938). The utilisation of methionine has been shown 

 by various workers (p. 610). Amino acid-supplements, in physiological concentra- 

 tion, 10'^ M, accelerate regeneration (Lecamp, 1942, 1947) but a number of pep- 

 tides have greater effects than the free amino acids, as also on growth in vitro 

 (Fischer, 1946). 



The synthesis of protein and the increase in total nitrogen in regenerating liver 

 have been followed by Paul et al. (1947), Novikoff and Potter (1948), Harkness 

 (1952), Tsuboi et al., (1954) and others, and those in healing skin by Williamson 

 and Fromm (1955). In liver the increase begins as early as twenty four hours 

 after partial hepatectomy, the R-phase being very short. Total nitrogen shows 

 a single smooth curve of increase, both in liver and in skin, so that the material 

 mobilised locally and that supplied systemically probably join a common pool. 

 The liver-proteins normally supply some of the material for skin-healing (William- 

 son and Fromm, 1955) but dietary protein or amino acids are used freely (Ham- 

 mett and Chapman, 1938; Localio et al., 1948, 1949; Bertolani et al., 1954; Baron 

 and Allison, 1954; Williamson and Fromm, 1952, 1954). The precise interaction 

 between dietary and body-protein needs clarification (p. 628). 



{b) Metabolism of nucleic acids 



The function of nucleic acids during the P-phase of regeneration is essentially 

 the same as in other kinds of growth (Chapter 3) and needs no detailed treatment 

 here. The synthesis of deoxyribosenucleic acid, DNA, runs roughly proportion- 

 ally to that of protein (Tsuboi, et al., 1954). It is a very reliable index of the num- 

 ber of nuclei, and therefore of cells, proliferated, and so of growth itself (Brues 

 et at., 1944; Davidson and Leslie, 1950). By contrast the maximal concentration 

 of pentosenucleic acid, PNA, is reached earlier than that of DNA and protein 

 (Hammarsten, 1951 ; Lombardo et al., 1953; Tsuboi et al., 1954) at the time when 

 protein is being synthesised most rapidly (Novikoff and Potter, 1948), just as in 



