Enzyme inhibition and the toxic action of moniliformin and other vinylogous alpha-ketoacids.
The inhibition of two thiamine-requiring enzymes by the potent mycotoxin, moniliformin (1-hydroxycyclobutene-3,4-dione), was investigated. Rat brain transketolase and pyruvate dehydrogenase were inhibited 25 percent by 10-9 M moniliformin. Studies carried out to determine if moniliformin causes enzyme inhibition by reaction with thiamine were negative. Varying the hydroxycyclobutenedione structure by substitution or ring expansion resulted in loss of toxicity and inhibition.
D000818:Animals; D001921:Brain / Q000201:enzymology; D003503:Cyclobutanes / Q000494:pharmacology*; D009183:Mycotoxins / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014174:Transketolase / Q000037:antagonists & inhibitors*
D003503:Cyclobutanes; D009183:Mycotoxins; D011768:Pyruvate Dehydrogenase Complex; C008539:moniliformin; D014174:Transketolase