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首页> 外文期刊>Life sciences >Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor.
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Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor.

机译：酮体影响巨噬细胞迁移抑制因子的酶活性。

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摘要

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.
机译：巨噬细胞迁移抑制因子（MIF）是一种众所周知的促炎细胞因子，具有令人困惑的酶活性：D-多巴色素和苯丙酮酸的互变异构转化。这些催化活性是否与MIF的多方面作用具有功能相关性，目前仍在审查中。然而，已经开始了针对MIF互变异构酶活性的药物研究。我们用分光光度法研究了几种抗炎化合物，可防止MIF催化丙酮酸苯丙酮酸的酮-烯醇（烯醇酶）和烯醇-酮（酮酶）转化。我们已经鉴定出酸性CH基团是针对MIF苯丙酮酸互变异构酶的抑制剂效能的标志物。在具有强酸性CH基的简单模型分子中，我们发现乙酰丙酮是最好的抑制剂，尤其是对酮酶活性的抑制剂。具有生理重要性的酮（酮体）也具有酸性CH基团，据报道具有一定的抗炎作用。在本文中，我们报道了酮体在体外优先抑制MIF的酮酶活性。未来的研究应解决这种相互作用是否可能在体内起作用，并描述其与MIF的细胞因子和非细胞因子作用的可能相关性。

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