Regulatory Mechanisms of Gene Expression by Carbohydrates.

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  • Yamada Kazuya
    Department of Biochemistry, Fukui Medical University
  • Noguchi Tamio
    Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University

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  • 炭水化物による遺伝子の発現調節機構
  • タンスイカブツ ニ ヨル イデンシ ノ ハツゲン チョウセツ キコウ

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Abstract

Dietary carbohydrates regulate the expression of genes involved in carbohydrate and lipid metabolism. Although this regulation may be mediated by insulin, there is a considerable amount of evidence indicating that carbohydrates or their metabolites, and not insulin itself, are directly involved in gene regulation. The L-type isozyme (LPK) gene of pyruvate kinase, an important glycolytic enzyme, is a good example. This gene is expressed in liver, kidney, small intestine, and pancreatic β-cells, and is stimulated by carbohydrates such as glucose and fructose at both the transcriptional and post-transcriptional levels. Two cis-acting regulatory elements named L-II and L-III are required for transcriptional stimulation of the LPK gene by carbohydrates. Although the L-III element is itself responsive to carbohydrates, L-II functions as an accessory element. Both nuclear factor 1 proteins and hepatocyte nuclear factor 4 bind to the L-II element. Further studies have suggested that the former is involved in carbohydrate stimulation of the LPK gene. However, the L-III element binding protein that is involved in carbohydrate regulation remains to be clarified. Available evidence suggests that the carbohydrate signaling pathway to the LPK gene includes a glucose metabolite, possibly glucose 6-phosphate or xylulose 5-phosphate, as well as phosphorylation and dephosphorylation mechanisms.

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