Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor

Macrophage migration inhibitory factor (MIF), a long known proinflammatory cytokine exhibits perplexing enzymatic activities: tautomeric conversion of d-dopachrome and phenylpyruvate. Whether these catalytic activities bear functional relevance regarding MIF's multifaceted roles is under curren...

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Bibliographic Details
Published in:Life sciences (1973) 2005-08, Vol.77 (12), p.1375-1380
Main Authors: Garai, János, Lóránd, Tamás, Molnár, Valéria
Format: Article
Language:English
Subjects:
Diketones
Enzyme Inhibitors - pharmacology
Humans
Intramolecular Oxidoreductases - antagonists & inhibitors
Intramolecular Oxidoreductases - metabolism
Ketone bodies
Ketone Bodies - pharmacology
Macrophage Migration-Inhibitory Factors - antagonists & inhibitors
Macrophage Migration-Inhibitory Factors - metabolism
Macrophages - drug effects
Macrophages - enzymology
MIF
Phosphopyruvate Hydratase - antagonists & inhibitors
Phosphopyruvate Hydratase - metabolism
Tautomerase
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Summary:Macrophage migration inhibitory factor (MIF), a long known proinflammatory cytokine exhibits perplexing enzymatic activities: tautomeric conversion of d-dopachrome and phenylpyruvate. Whether these catalytic activities bear functional relevance regarding MIF's multifaceted roles is under current scrutiny. Nevertheless, intense search has already started for pharmacological agents that target MIF's tautomerase activity. We have probed several antiinflammatory compounds against keto–enol (enolase) and enol–keto (ketonase) conversion of phenylpyruvate by MIF with spectrophotometry. We have identified acidic CH groups as markers of inhibitor potency toward MIF phenylpyruvate tautomerase. Among simple model molecules with strong acidic CH groups we found acetylacetone the best inhibitor particularly against the ketonase activity. Ketones of physiological importance – ketone bodies – also feature acidic CH groups and have been reported to exert certain anti-inflammatory effects. In this paper we report that ketone bodies inhibit preferentially the ketonase activity of MIF in vitro. Future studies should address whether such an interaction might operate in vivo and delineate its possible relevance concerning cytokine and non-cytokine roles of MIF.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2005.03.010