Suicide enzyme-inactivator

As these inhibitors owe their activity to the kcat term (i.e., the enzyme s usual mode of action) they have been designated "kcat inhibitors" by Rando (1), while Abeles and Maycock (2 ) have used the term "Suicide Enzyme Inactivators" because the enzyme, in accepting such a "booby-trapped" substrate commits suicide by its own mechanism of action. 

Abeles and Maycock (2 ) and Walsh (5) as well as to a symposium proceedings which offers the most recent and comprehensive reviews in the area (6 ). This review will restrict itself to the irreversible inhibition of pyridoxal phosphate (PyCHO)-dependent enzymes, a class of enzymes which has proven to be generally susceptible to inhibition by suicide enzyme inactivators. 

In conclusion, suicide enzyme inactivators offer a powerful method for the selective irreversible inhibition of enzymes. Although this review has concentrated on pyridoxal phosphate-dependent enzymes the approach is also valid for the irreversible inhibition of other types of enzymes (6 ) and may offer a means for the rational design of therapeutically-useful substances. 

Inhibition of xanthine oxidase by allopurinol, an analogue of hypoxanthine. Nv and Cg of hypoxanthine are reversed in allopurinol. Allopurinol, a suicide enzyme inactivator, is converted to alloxanthine, which binds tightly to the active site of the enzyme via Mo and interrupts the reoxidation of Mo + to Mo " needed to initiate the next catalytic cycle. 

Alloxanthine (suicide enzyme-inactivator of xanthine oxidase)... 

Mechanism of action of S-adenosylhomoeysteine hydrolase (enzyme) and its inhibition by deoxyadenosine. (a) The enzyme uses enzyme-bound NAD+ to temporarily oxidize substrate and eventually hydrolyze it to adenosine and homocysteine. [Reproduced with permission from R. H. Abeles, Suicide enzyme inactivators. Chem. Eng. News 61(38), 55 (September 19, 1983). 1983 by the American Chemical Society.] (b) Deoxyadenosine, a suicide substrate, is also oxidized by the enzyme with the formation of a ketosugar, which undergoes decomposition, with the product dissociating from the enzyme and leaving the enzyme in the reduced state (NADH). 

Suicide enzyme inactivators, R. H. Abeles, 1983, Chem. Eng. News, 61 4856. 

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