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首页> 外文期刊>Biochimica et Biophysica Acta. Protein Structure and Molecular Enzymology >Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae: genetic regulation
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Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae: genetic regulation

机译：酵母酿酒酵母中硫胺素代谢和硫胺素二磷酸依赖性酶的遗传调控

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The yeast Saccharomyces cerevisiae utilises external thiamin for the production of thiamin diphosphate (ThDP) or can synthesise the cofactor itself. Prior to uptake into the cell thiamin phosphates are first hydrolysed and thiamin is taken up as free vitamin which is then pyrophosphorylated by a pyrophosphokinase. Synthesis of ThDP starts with the production of hydroxyethylthiazole and hydroxymethylpyrimidine. Those are linked to yield thiamin phosphate which is hydrolysed to thiamin and subsequently pyrophosphorylated. The THI genes encoding the enzymes of these final steps of ThDP production and of thiamin utilisation have been identified. Their expression is controlled by the level of thiamin and a number of regulatory proteins involved in regulated expression of the THI genes are known. However, the molecular details of the regulatory circuits need to be deciphered. Since the nucleotide sequence of the entire yeast genome is known we can predict the number of ThDP-dependent enzymes in S. cerevisiae. Eleven such proteins have been found: pyruvate decarboxylase (Pdc, three isoforms), acetolactate synthase, a putative α-ketoisocaproate decarboxylase with a regulatory role in ThDP synthesis and two proteins of unknown function form the group of Pdc related enzymes. In addition there are two isoforms for transketolase as well as the E1 subunits of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase. Expression of most of these genes is either induced or repressed by glucose. Surprisingly, it has been found recently that expression of one of the genes for Pdc is repressed by thiamin. In addition, the regulatory protein Pdc2p was shown to be required for high level expression of both the THI and the PDC genes. Apparently, the production of ThDP and of the enzymes using this cofactor is coordinately regulated. Future research will focus on the elucidation of the molecular mechanisms of this novel type of regulation.
机译：酵母酿酒酵母利用外部硫胺素来生产二磷酸硫胺素（ThDP），或者可以合成辅助因子本身。在摄入细胞之前，首先将硫胺素磷酸酯水解，并以游离维生素的形式吸收硫胺素，然后将其通过焦磷酸激酶进行焦磷酸化。 ThDP的合成从羟乙基噻唑和羟甲基嘧啶的生产开始。那些被链接以产生硫胺磷酸酯，其被水解成硫胺素，随后被焦磷酸化。已经鉴定出编码ThDP产生和硫胺素利用这些最终步骤的酶的THI基因。它们的表达受硫胺素水平的控制，并且已知许多参与THI基因表达调控的调控蛋白。但是，需要弄清楚调节电路的分子细节。由于已知整个酵母基因组的核苷酸序列，因此我们可以预测酿酒酵母中ThDP依赖性酶的数量。已经发现了11种这样的蛋白：丙酮酸脱羧酶（Pdc，三种同工型），乙酰乳酸合酶，在ThDP合成中起调节作用的推定的α-酮异己酸脱羧酶和两种功能未知的蛋白形成了与Pdc相关的酶。另外，转酮酶以及丙酮酸脱氢酶和2-氧戊二酸脱氢酶的E1亚基有两种同工型。葡萄糖诱导或抑制了大多数这些基因的表达。令人惊讶地，最近发现，硫胺素可抑制Pdc基因之一的表达。另外，显示出调节蛋白Pdc2p对于THI和PDC基因的高水平表达都是必需的。显然，使用该辅因子可调节ThDP和酶的产生。未来的研究将集中于阐明这种新型调节的分子机制。

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