14 



W. A. DE VOOGD VAN DER StRAATEN 



lactate -^'^^ pyruvate " 



flavoprot red 

 ftavoprot c 



oxalo^acetate citrate 

 NADH aconitase 

 'r^oj^'^^o ,50 citrate 



fumarate \^nadp 



/ C Deh. X 



lytic pathway, the pentose phosphate cycle and the Krebs cycle are operative. 



2. However concerning the oxidative phosphorylation nearly nothing is known. 



3. The activities of the pentose shunt dehydrogenases are suprisingly high in dia- 



physeal rabbit bone tissue as com- 



glucose /^ gtuco5e-6-P <~ poiysaccha- pared with e.g. kidney, liver and 



brain tissue. Moreover the strik- 

 ingly high relative activity of pyri- 

 dine nucleotide transhydrogenase 

 — being as it is, involved in the 

 reoxydation of NADPH — seems 

 to underline the importance of the 

 NADP dependent dehydrogenases 

 in bone. 4. On the other hand the 

 relatively low activity of Succinic 

 Cytochrome C reductase suggests a 

 less important role of the tri- 

 carboxylic acid cycle. 5. Concern- 

 ing the citrate metabolism, espe- 

 cially under the influence of PTH, 

 the problem about the balance be- 

 tween citrate synthesis and oxida- 

 tion is still open to some contro- 

 versy. 6. Finally, in this picture 

 we meet already some connections 

 between carbohydrate metabolism 

 and protein synthesis, especially 

 collagen synthesis. These connec- 

 tions concern carbohydrate iner- 

 mediates being precursors of some 

 amino acids and furthermore the 

 ribose synthesis being prerequisite 

 to RNA synthesis and so indirectly 

 to protein synthesis; see Fig. 1. 

 Now although the data concerning the action of PTFi on bone tissue belong to a 

 subgroup of our universe of discourse, they are of direct relevance, because they 

 reveal in all probability the key points of bone metabolism. Moreover, though not 

 being essential, work on the main pathways is mainly done by students in the PTE 

 field. 



And so an essential contribution to our picture is Hekkelman's hypothesis stating 

 that PTE induces a decrease of the amount of NADP and/or NADPH available for 

 catabolic processes in the bone cells (Hekkelman, 1963, 1965). His argument hinges 

 on phenomena concerning the extractahility of Isocitric dehydrogenase from dia- 

 physeal bone homogenates and more specially on the influence of NADP or NADPH 

 — additional or naturally present — on this extractahility. In fact he did no direct 

 determinations of the cofactors mentioned. 



It will be interesting now to compare this picture with a number of observations 

 communicated at the 2nd Parathyroid symposium held in 1964 in the Netherlands: 



CO2 



NADPH 

 A-CO2 



aketoglutarate 



ammo acids 



Simplified scheme of the mam metabolic pathways 



Fig. 1. A simplified scheme of the main metabolic pathways, 



according to J. W. Hekkelman: Bone metabolism and the action 



of parathyroid extract, 1963. Note: NAD(H) = DPN(H): 



NADP(H) = TPN(H) 



