KONRAD BLOCK 



Recognition of these reactions which are independent of the nutritional 

 state of the animal illustrates the very limitations to which balance 

 experimentation in the intact animal is subject. 



In considering the in vivo relationships of steroids, it is important 

 to bear in mind that the body possesses a store of cholesterol in every 

 cell. If cholesterol were the parent substance for all other steroids 

 (bile acids and steroid hormones), the precursor would be available in 

 amounts which are large in comparison with the quantities of bile acids 

 and hormones normally produced. Increase of the available choles- 

 terol supply by dietary addition can, therefore, be expected to affect 

 these conversions but little. With labeled cholesterol, the role of this 

 sterol as a precursor of bile acids and of the excretion form (pregnane- 

 diol) of at least one steroid hormone (progesterone) could be verified 

 (2,3). For the interpretation of the experiment, the quantities both 

 of precursor administered and of conversion product isolated are 

 immaterial. Appearance of the isotopic label in the reaction product 

 is sufficient proof of the occurrence of the postulated reaction, provided 

 that the uptake of isotope is not due to an unspecific reaction. When 

 deuterium is the isotope employed, the possibility that the reaction 

 product received its isotope by unspecific reactions such as exchange 

 with the body fluids must be excluded. The quantitative importance 

 of the conversion can be evaluated from the relative concentrations of 

 isotope in the circulating precursor and the product formed. 



Degradation of Fatty Acids 



The apparent inability of in vitro systems to synthesize or degrade 

 lipids may well be a consequence of the fact that the metabolism of 

 lipids requires the presence of intact cells. The enzyme systems 

 involved have remained entirely unknown, and the study of inter- 

 mediary fat metabolism has therefore been carried out primarily with 

 intact animals. Stable isotopes found their first biological application 

 in this field and piomise to yield further information particularly when 

 carbon C^^ becomes readily available. The recent observation that 

 lipid synthesis can be demonstrated to occur in surviving liver if marked 

 test substances are employed may facilitate a more detailed study of 

 reaction mechanisms which are not profitably investigated by experi- 

 mentation with intact animals. 



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