がん細胞の糖代謝を特異的に担うヘキソキナーゼの同定とその機能解析

• 篠原 康雄

書誌事項

タイトル別名

• Identification and Characterization of Hexokinase Isozyme Predominantly Expressed in Malignant Tumor Cells
• ガン サイボウ ノ トウ タイシャ オ トクイテキ ニ ニナウ ヘキソキナーゼ ノ ドウテイ ト ソノ キノウ カイセキ

抄録

Tumor cells show a higher glycolytic rate than normal cells. Of glycolytic enzymes, the activity of hexokinase, known as a rate limiting enzyme in glycolysis, is amazingly high in malignant tumor cells. In mammals, four isozymes of hexokinase are expressed but the question which isozyme is responsible for the high hexokinase activity observed in tumor cells was not yet clearly answered. By Northern blot analysis, we found that the type II isozyme, which is only slightly expressed in normal heart, muscle and adipose tissue, was remarkably expressed in malignant tumor cells. We next tried to understand how the expression of type II hexokinase gene is regulated in tumor cells. For this purpose, we first isolated the type II hexokinase gene and characterized its structural features. We further investigated the regulatory machanisms of the expression of type II hexokinase in tumor cells. Results indicate the potential involvement of a serum responsive factor in the regulation of the expression of type II hexokinase in tumor cells. In addition to the remarkable expression, binding of the type II hexokinase to mitochondria is another characteristic of tumor cells, however, the physiological meaning of hexokinase binding to mitochondria was not yet fully understood. Our results clearly showed that the mitochondria-bound hexokinase utilize mitochondrially generated ATP more preferentially under normal conditions. However, when the rate of extramitochondrial ATP generating system (glycolysis) exceed that of mitochondrial ATP generating system (oxidative phosphorylation), the mitochondria-bound hexokinase utilize extramitochondrial ATP. This result indicates that the hexokinase binding enables a cross talk between oxidative phosphorylation and glycolysis.

収録刊行物

• 薬学雑誌

  薬学雑誌 120 (8), 657-666, 2000

  公益社団法人 日本薬学会

キーワード

• hexokinase
• energy metabolism
• mitochondria
• tumor cell

詳細情報

• CRID: 1390282681132569856
• NII論文ID: 110003648849
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi1947.120.8_657
• ISSN: 13475231
• ISSN: 00316903
• ISSN: http://id.crossref.org/issn/00316903
• NDL書誌ID: 5422682
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5422682
• Web Site: https://www.jstage.jst.go.jp/article/yakushi1947/120/8/120_8_657/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2001024611
• データソース種別:
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  • NDL
  • Crossref
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