AEROBIC METABOLISM OF CARBOHYDRATE 133 



Effect on Respiratory Quotient (R.Q.) 



The change of R.Q. brought about by iodoacetate might provide some 

 information as to the metabolic disturbance produced if care is taken in 

 the interpretation of such changes in complex systems. If iodoacetate blocks 

 the EM pathway specifically and if the cells are oxidizing carbohydrates 

 and other substrates, one would expect a fall in the R.Q., since the carbo- 

 hydrate fraction of the metabolism should be reduced. However, if an ac- 

 tive pentose-P cycle is present, an increase in the R.Q. is possible, especially 

 if some of the NADPH is oxidized by any pyruvate present. Actually, the 

 change in R.Q. induced by iodoacetate is often quite small (Table 1-21); in 

 perhaps ten of the tissues in the table the change is insignificant (in some 

 of them the iodcracetate affects none of the tissue's metabolic activities, e.g., 

 respiration, so that insufficient concentration due to poor penetration may 

 be the reason for the lack of effect on the R.Q.). In many cells there is a 

 definite drop in the R.Q., especially when glucose is provided in the medium; 

 if the metabolism is endogenous, there may be little carbohydrate being 

 oxidized so that the effect on the R.Q. cannot be predicted. Corn root is the 

 only tissue showing a really marked increase in the R.Q. due to iodoacetate 

 when glucose is present, although cat and dog heart and cat brain show 

 slight increases. Although accurate figures are not available, it is clear that 

 the R.Q. is also decreased in rhubarb leaves (Morrison, 1950), several yeasts 

 (Spiegelman and Nozawa, 1945), and dog heart (Burns and Cruickshank, 

 1937). An important factor often neglected is the presence of various inter- 

 mediates or products of carbohydrate metabolism, so that, after iodoacetate 

 is added, oxidation of these substances can continue for a time. For example, 

 ethanol would be completely oxidized with an R.Q. of 0.67 and might con- 

 tribute to reducing the over-all R.Q., while lactate would be completely 

 oxidized with an R.Q. of 1.0, both lactate and pyruvate giving R.Q.'s higher 

 than 1.0 if the oxidation is incomplete, thereby contributing to a rise in 

 the R.Q. By themselves, R.Q. studies do not tell us a great deal about the 

 action of iodoacetate, but in conjunction with other data may have some 

 value in elucidating the complex metabolic changes which occur. 



Effects on the General Patterns of Glucose Oxidation and Metabolism 



There now remain to be discussed some of the effects on carbohydrate 

 metabolism not covered in the previous sections to round out our picture 

 of the alterations produced by iodoacetate. One problem is the synthesis 

 of di- and polysaccharides from glucose. If glucose oxidation is impaired 

 by iodoacetate, will relatively more go into synthetic pathways? The an- 

 swer seems to be definitely in the negative. The following syntheses are 

 readily depressed by iodoacetate: glycogen in yeast (Briicke, 1933), in rat 

 liver slices (Bach, 1939), and in rat diaphragm (Haft and Mirsky, 1952); 



