16 



W. A. DE VOOGD VAN DER StRAATEN 



contrary NADPH decreases under the influence of PTE one gets the feeling that the 

 oxidized and the reduced state do not keep the simple relation to one another one 

 should perhaps suppose to exist in an uncomplicated chain of oxido-reductions. In 



Biosynthesis NADP 



PTE eltect of oddiliono 

 NAD and NADP 



NADP 



(12S* increased) ' 



Substr(H)\ + (nADp' 



(decreased 07x) 



^ nad(h) 



r^ 1 Cytochrome 



I '\ y\ system 



1 (t^ ) NAD -< X etc 



♦ \<y , (no change) 



•- NADP(h) ^+ Substr(ox) 



(decreased 07 x) 



Fig. 3. The concept of 2 NADP fractions; the 



the 2"'! Parathyroid symposium, 1964. Moreove 



is given. Finally the supposed mechanisr 



Isonicoli 



ATP 



GMP 



scheme presents some findings of Van Reen ('■') communicated at 

 the function of NADP and NAD in dehydrogenation reactions 

 of action of a number of PTE antagonizers is indicated 



fact the decrease of NADPH alone, could possibly point to a hormone induced 

 increase of pyridine nucleotide transhydrogenase activity as this enzyme takes away 

 the hydrogen from the NADPH and transports this hydrogen to NAD. However in 

 trying to solve the problem from this side one finds there is no explanation for the 

 increase of NADP. The "unifying concept" then could be, that we have to dis- 

 criminate between the NADP "present" and the NADP really available for the 

 catabolic enzymes in the metabolic machinery. In align with this idea we suppose 

 that the observed rise of the NADP level concerns the fraction of NADP "present 

 but not available". To go one step further, one could suppose that the "screen" 

 between both fractions protects the non available fraction against enzymatic break- 

 down thus accounting for an increase. Behind this idea we find the concept of 

 cellular compartmentalization. Clearly at the moment this concept is, in our situation 

 only a formalism, although Hekkelman and I are speculating that the non available 

 fraction, if existing at all, could be hidden in the nucleus of the cells. 



In relation to what I have said I would like to report furthermore an important 

 observation made by (Cohn and Griffith, 1965) working with slices of the distal 

 ends of rabbit femora. They found NAD and NADP specifically capable of stimu- 

 lating the C^^Oo evolution from Fumarate-1,4-C**. Using Citrate-1,5-Ci^ this effect 

 failed to appear. In slices from PTE pretreated animals the CO., evolution is less 

 than in control slices and this hormone effect is not overcome by NADP. Further 

 analysis revealed that the rate of conversion from Fumarate to Malate is independent 

 of NADP, however in the presence of NADP less Malate accumulates. This already 



