Formation of Fatty Acids 283 



Fraser: I noticed in Dr. Gurin's slides that the insuHn effect was not 

 found in diabetic animals. Was insulin added to the slice or to the 

 animal? 



Gurin: In our experiments insulin was added to the slices. 



Fraser: Have you tried adding insulin before using the slices? 



Gurin: We have not done that, but I feel sure that it would work. 



Popjak: Have you any evidence that the whole carbon chain of the 

 short chain acids is used in fatty acid synthesis? It might be that the 

 short chains are broken down to Cg units first. I am demolishing my 

 own ideas, but I wonder if there is any evidence for it. 



Another point, if we are right that fatty acids are synthesized from 

 glucose after it has been broken down to pyruvate and then to a Ca 

 unit, then it seems possible that it is the latter step which must be 

 blocked in diabetes, i.e. that pyruvate cannot yield Cg units. 



Gurin: We have no evidence for the direct utilization of the short 

 chain fatty acids and we do have evidence that they are broken down to 

 2 carbon fragments. It would perhaps be better for Dr. Bloch to 

 answer this, for he and Dr. Zabin have shown that in certain conditions 

 there is a preferential condensation of 2 carbon fragments onto palmitic 

 acid to form stearic acid labelled primarily in the carboxyl carbon. 

 That would fit in very nicely, I believe, with what you suggest. Perhaps 

 both types of condensations occur. Certainly there is a wide distribution 

 of isotope throughout the chains of long chain fatty acids. 



With regard to the site of blockage in diabetes, I can only say that 

 it is attractive to think of the block occurring between pyruvate and 

 Ca fragments. We have done one preliminary experiment on this. We 

 have incubated liver slices with radioactive pyruvate, using slices from 

 normal and alloxan-treated rats in the presence of carrier non-radio- 

 active acetoacetate. We get more isotope into the acetoacetate with 

 normal liver slices than we do with slices from the diabetic animals. 

 These are preliminary experiments which I think do not mean much; 

 there is so much variation from liver to liver. They need repeating 

 many times. 



Folley: Have you tried in vitro growth hormone on your liver slices 

 from Houssay-animals, or injections of growth hormone into them? 



Gurin: We have injected growth hormone into Houssay-animals 

 and once again this inhibited the liver's ability to synthesize fat. We 

 have done one other experiment: you will remember I said that we 

 could get an insulin effect in vitro with liver slices from normal animals; 

 we can neutralize or at least diminish the stimulating effect of insulin 

 by previous treatment of the slices with growth hormone. 



Young: I think that the suggestion that the formation of glycerol 

 may be a rate-limiting factor in fat synthesis is of great interest and 

 needs much consideration. 



May I make one general comment on the Krebs or citric acid or tri- 

 carboxylic cycle? Now that citric acid is firmly established back on the 

 cycle, can we agree on its proper title? Professor Krebs originally 

 called it the citric acid cycle and I understand he prefers not to have it 

 called after him. Whilst his modesty should not deter us from calling 



