INHIBITION OF XANTHINE OXIDASE 279 



AF for displacement of succinate 

 (kcal/mole) 



EH2I EHI EI 



D-Tartrate —0.5 +0.4 



L-Tartrate —0.5 +0.8 +0.7 



meso-Tartrate — 1.6 — 2.8 — 3.3 



The fumarase from, liver is inhibited differently from the heart enzyme, 

 in that mesaconate (methylfumarate) is inactive whereas citraconate 



H3C ^COO' H COO" V*^ 



C C C=CH2 



II II I ' 



/C^ . ^C^ CH3 



H COO H3C H i,^- 



Citraconate Crotonate Itaconate 



(methylmaleate) inhibits well (Jacobsohn, 1953). Itaconate inhibits less 

 potently and crotonate even less potently (about the same as succinate). 

 The fact that crotonate inhibits at all is interesting, in that it suggests 

 that one C00~ is sufficient if a double bond is present. czs-Aconitate and 

 ^raws-aconitate inhibit equally and weakly. DL-/5-Fluoromalate inhibits com- 

 petitively the conversion of malate to fumarate by fumarase (Krasna, 

 1961). Assuming that both optical isomers inhibit equally (which may 

 not be true), K^ = 28 mM, and K„^ for malate is 3.5 niM. The inhibition 

 of malate dehydrogenase is much stronger, if ^ being 0.16 mM, which may 

 be compared to a K,,^ of 11 mM for malate. 



INHIBITION OF XANTHINE OXIDASE 

 BY PURINE ANALOGS AND PTERIDINES 



Some potent and specific inhibitors of xanthine oxidase have been dis- 

 covered and have proved to be interesting not only on the enzyme level 

 but because of the disturbances in purine metabolism produced in whole 

 animals. Xanthine oxidase catalyzes the oxidation of hypoxanthine and 



N N' 



Hypoxanthine Xanthine Uric acid 



