Murray M, Greenberg M L
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
Mol Microbiol. 1997 Aug;25(3):541-6. doi: 10.1046/j.1365-2958.1997.4881840.x.
Inositol monophosphatase is a key enzyme in the de novo biosynthesis of inositol and in the phosphoinositide second-messenger signalling pathway. Inhibition of this enzyme is a proposed mechanism for lithium's pharmacological action in bipolar illness (manic depression). Very little is known about how expression of this enzyme is regulated. Because the yeast Saccharomyces cerevisiae has been shown to be an excellent model system in which to understand the regulation of inositol metabolism, we characterized inositol monophosphatase in this yeast. Lithium inhibited monophosphatase activity in vitro. Growth in the presence of inositol resulted in increased expression of the enzyme in vivo, although inositol had no effect on enzyme activity in vitro. The inositol effect was apparent when cells were grown in glucose but not in glycerol/ethanol. Monophosphatase activity was derepressed as cells entered stationary phase. This effect was apparent only during growth in glucose plus inositol. The results demonstrate that S. cerevisiae monophosphatase is inhibited by lithium and regulated by factors affecting phospholipid biosynthesis.
肌醇单磷酸酶是肌醇从头生物合成以及磷酸肌醇第二信使信号通路中的关键酶。抑制该酶是锂盐治疗双相情感障碍（躁狂抑郁症）药理作用的一种推测机制。关于这种酶的表达是如何调控的，目前所知甚少。由于酿酒酵母已被证明是理解肌醇代谢调控的优秀模型系统，我们对这种酵母中的肌醇单磷酸酶进行了表征。锂盐在体外抑制单磷酸酶活性。在肌醇存在的情况下生长会导致该酶在体内的表达增加，尽管肌醇在体外对酶活性没有影响。当细胞在葡萄糖中生长而非在甘油/乙醇中生长时，肌醇的这种作用很明显。随着细胞进入稳定期，单磷酸酶活性被解除抑制。这种效应仅在葡萄糖加肌醇的生长过程中明显。结果表明，酿酒酵母单磷酸酶受到锂盐抑制，并受影响磷脂生物合成的因素调控。
