Studies with Deuterium Steroids 39 



do not. Do you think that it is possible or Hkely that the metaboUtea 

 occur in the faeces rather than in the urine? 



Gallagher: In lower animals I think it's rather likely. I am very 

 certain that it doesn't happen with testosterone in man. We had come 

 to that conclusion from the deuterium work, and have recently confirmed 

 with carbon-labelled materials that no radioactivity appears in the 

 faeces. Progesterone in the mouse or in the rat is metabolized in part 

 at least with loss of the side chain. In other words, when you study 

 pregnanediol alone you're looking for only a portion of the end-products 

 of progesterone metabolism. I feel that in most hormones of the type 

 of progesterone, testosterone, and cortisone, some metabolic process 

 will open Ring A, but I have no positive evidence for this view at the 

 moment. 



Rittenberg: As I understand it, the platinum catalysed exchange 

 in cholesterol resulted in deuterium at the 6, 26 and 27 positions 

 exclusively. Would you care to speculate on the mechanism responsible 

 for this curious reaction. 



Gallagher: When the double bond of cholesterol w^as reduced there 

 was a loss of deuterium from the compound, i.e. the cholestanol obtained 

 had about • 5 atoms of deuterium per molecule less than the cholesterol. 

 Conversely, when cholesterol is saturated with deuterium in acetic 

 acid-d more than the expected 2 atoms of D appear in the product. 

 This means, we feel, that when carbon atom 6 forms a complex with 

 the catalyst, the hydrogen or deuterium at that position becomes labile 

 and exchanges with the hydrogen or deuterium of the medium. You 

 must have hydrogen gas to achieve this because in the absence of 

 reduction no change or only a very minor one occurs. In the exchange 

 reaction it is therefore readily understandable that this position would 

 undergo exchange. Why only the terminal methyl groups in the side 

 chain exchange hydrogen is at present unknown. Before we found these 

 interesting facts we had thought w^e might make some generalizations 

 about the platinum catalysed exchange reaction, and had studied a 

 great many different compounds. We found that the more unsaturated 

 the compounds, the more functional groups they contained, the more 

 exchange could take place; but as we accumulated more and more 

 evidence, it became clear that each compound behaved uniquely. 

 Apparently, the catalyst-substance complex determines not only the 

 amount but also the distribution of the isotope. 



Bloch: Do you lose all the ring deuteriums in the conversion of 

 cholesterol to cholestenone? 



Gallagher: Practically speaking, yes, you lose all of it after equilibra- 

 tion with aqueous alkali. 



Bloch: I am just wondering how the data which we obtained some 

 years ago on the conversion of deuterium cholesterol to pregnanediol 

 or to the bile acids would appear in terms of these results. We assumed 

 at the time that several hydrogens would be lost by enolization. Such 

 losses would occur if a A'^'^ unsaturated ketone were an intermediate. 

 One would expect a considerable loss since you also lose deuterium from 

 the isopropyl group of the side chain. 



