494 5. QUINONES 



inhibition is directly on protein synthesis or is a simple reduction in the 

 energy-supplying reactions. Menadione does not alter the incorporation of 

 formate or glycine into the purines of the acid-soluble nucleotides or of 

 DNA, but reduces the uptake into RNA purines, and this is accompanied 

 by an increase in the pyrimidines at the expense of the purines (Marrian, 

 1959). It was thought that this might explain the radiosensitizing action, 

 since X-irradiation interferes predominantly with DNA synthesis. 



Thyroid Metabolism 



Diiodotyrosine and thyroxine formation in thyroid slices is inhibited 

 around 80% by 1 mM p-benzohydroquinone (Taurog et at., 1945). Since 

 the monomethyl ether of p-benzohydroquinone inhibits similarly, and 

 inasmuch as several compounds related structurally to thyroxine also in- 

 hibit it is likely that the inhibition is not directly related to a quinone struc- 

 ture. However, it was suggested that the ease of oxidation has something 

 to do with the inhibition and that the blocked step is probably an oxida- 

 tive one. The uptake of I^^^ into thyroid slices is depressed 60-90% by 

 1 mM p-benzohydroquinone, menadione, menadiol-diP, and hydrolapachol 

 (Shngerland, 1955). The site of action is presumably on the uptake process, 

 since the incorporation of I^^^ into the proteins of subcellular fractions of 

 thyroid is quite markedly stimulated by several quinones at 0.5 mM (see 

 accompanying tabulation), although lawsone and phthiocol are inhibitory 



(Tong and Chaikoff, 1960, 1961). There is also some stimulation of I^^i 

 incorporation into pepsin and seralbumin nonenzymically, and it is likely 

 that the mechanism involves the oxidation of the iodide to Ig", HOI, or 

 IOH2+ prior to the incorporation. Williams (1961) also noted that mena- 

 dione at 0.03-0.1 mM increases the amount of I^^^ bound in thyroid slices. 

 The situation here is probably complex and there are several ways in which 

 the quinones can act. It is not known if the effects on I^^^ binding are related 

 to the formation of thyroxine. 



