4 Sir Hans Krebs 



added, but there are considerable increases when acetate, 

 pyruvate or intermediates of the tricarboxyHc acid cycle are 

 added. 



Let us now consider the factors which Hmit the rate of 

 oxygen consumption in the heart muscle suspension to which 

 no substrate has been added, but which contains much 

 oxidizable material in the form of carbohydrate and lactate. 

 The fact that the oxygen consumption in this system can be 

 increased by the addition of suitable substrates proves that 

 the oxidizing capacity, i.e. the electron transport system from 

 reduced diphosphopyridine nucleotide (DPN) to Og, is not 

 used to the full, and is thus not a limiting factor in respiration. 

 What, then, is the limiting factor? 



The reactions between oxygen and substrates in this 

 system are known to involve iron porphyrins, flavoproteins 

 and pyridine nucleotides. Whilst it is not possible to draw up 

 a comprehensive sequence of reactions, a simplified list 

 indicating the types of reactions which occur can be formu- 

 lated. These are the following: 



substrate + pyridine nucleotide^,^ -> substrate^^ + pyridine nucleotide^gj 



DPN„,+TPN*, -.DPN,,, +TPN„, 



DPN^gj + flavoprotein^,^ -> DPN^^ + flavoproteinj.gj 



substrate + flavoprotein^j^ -^ substrate^^ + flavoproteinj,,, 



flavoproteinjgj + flavoprotein^^ -> flavoprotein^j + flavoproteinJJ, 



flavoprotein^g, + 2Fe^+-porphyrin -> flavoprotein^^ + 2Fe2+-porphyrin + 



2H+ 



Fe^+'porphyrin^ + Fe^+.porphyrin"^ -> Fe^+'porphyrin" + Fe^+-porphyrin" 



2Fe2+-porphyrin + 2H+ + ^O^ -> 2Fe3+-porphyrin + HgO 



♦ Triphosphopyridine nucleotide. 



A still further simplified version, indicating the main steps, 

 is the following scheme: 



substrate (most) 

 pyridine nucleotide 



substrate > flavoprotein 



(succinate, fatty | 



acetylcoenzyme A) iron porphyrin 



