V METABOLIC CHANGES 615 



In ontogenesis (Yao, 1950; Karczmar and Berg, 1951; Krugelis et al., 1952) the enzyme 

 becomes maximally active only in later stages, and the correlation with differentiation 

 therefore seems established (Needham, 1952). Nevertheless there remains much obsurity 

 and conflict of evidence. Gould and Gold (1951), administering the enzyme even to ani- 

 mals depleted of it, could detect no acceleration of regeneration, and regeneration was 

 normal in the presence of inhibitors of alkaline phosphatase. 



(d) Metabolism of sulphur compounds 



Recent results (Christensen and Streicher, 1948; Firket, 1950; Layton, 1950, 

 1951 ; Frederic, 1952) support earlier evidence (Needham, 1952) that there is an 

 increase in number of free SH-groups during the R-phase. This is characteristic of 

 denaturation-changes in proteins (Joly, 1955), during which the SH-groups also 

 become capable of activity in a more acid pH-range, while the proteins become 

 more sensitive to proteolytic and other agents. The R-phase therefore probably 

 involves a reversible denaturation of proteins, locally, The SH-concentration in 

 the plasma declines during the first twenty-four h. after laparotomy (Schacter^^a/., 

 1952), possibly owing to increased uptake by the wovind-region, and that of the 

 liv^er declines at this time (Beck and Linkenheimer, 1952), for the same reason 

 (Fromm, 1955). Maloeuf (ig36a) found the concentration of gltitathione (GSH) 

 to be below normal in a three weeks-old tail-regenerate oi Rana clamitans, which is 

 consistent with the results of Okunev (1932), Orechovitch (1934, 1936) and 

 Ryvkina (1940) showing that the redticed form, SH, decreases in the later stages 

 of regeneration, probably through reoxidation to the -SS-form. 



That these SH-compounds play an important part in regeneration is proved 

 by the accelerating, and the protein-sparing, effect of supplements of the sulphur- 

 containing amino-acids (Crofts and Peters, 1945; Williamson and Fromm, 1955). 

 Regeneration-rate is probably more closely correlated with sulphur- than with 

 nitrogen-metabolism, i.e. with these amino acids more than with any others 

 (Williamson et al., 1951). This conclusion is confirmed by work on cells growing 

 in vitro (Fischer, 1946; HafFen and Wolff, 1953). Morgulis and Green (1932) 

 claimed that added stilphur compounds do not accelerate regeneration in the 

 polychaete Podarke, but they did not use physiological SH-compounds. Their 

 results with cystine, the oxidised dimer of cysteine, indicate a slight acceleration, 

 which is to be expected, — in the P-phase. However, Gershbein and Labow (1953) 

 also have failed to detect acceleration of liver-regeneration in rats by cysteine, or 

 by GSH, as 0.75% of the diet. Thiouracil did promote regeneration btit this could 

 have been indirectly, via its effect on the thyroid. Orechovitch (1936) showed 

 that the catheptic activity of some regenerating tissues is not accelerated by SH- 

 compoimds, probably because they are already fully activated by the autogenous 

 increase in -SH, and this may explain also the results of Gershbein and Labow. 



Ryvkina (1940) has pointed out that the maximal concentration of SH-com- 

 pounds is reached later than the maximum of proteolytic activity, and they prob- 

 ably also promote cell-division, as in other types of growth (Voegtlin and Chalk- 

 ley, 1930; Rapkine, 1931 ; Harris, 1953). SH-groups are very abundant in many 

 enzymes (Barron, 1949) and therefore they probably also have a number of other 

 functions in regeneration. In addition the disulphur, -SS-, bridges of cystine are 

 essential structural components of synthesized keratin and other insohible proteins 



Literature p. 64g 



