The mechanism of -glucose formation by G6Pase of liver and inhibition of the enzyme
| Project/Area Number |
62570130
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Faculty of Medicine, Osaka University |
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Principal Investigator |
FURUYA Eisuke Faculty of Medicine, Osaka University, Associate Professor, 医学部, 助教授 (00028523)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | G6Pase / G6P translocase / G6Pase inhibition by F1P / glycogen synthesis / G6PアーゼF1Pによる阻害 / フルクトース / G6PアーゼのF1Pによる阻害 / 潅流肝 / G6Pアーゼ / 活性調節 / 1・デオキシグルコース6・りん酸 |
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| Research Abstract |
1. regulation of g6pase activity
It is widely believed that there is no regulatory mechanism of glucose 6-phosphatase activity in ER membrane of liver. In the present investigation, we obtained the results which supported the existence of the control mechanism.
In perfused rat liver, glycogen was synthesized at very poor rate even under the high concentration of glucose. When 2 mM fructose was administrated with glucose, active glycogen synthesis was observed. Based on the good correlations observed between the rate of glycogen synthesis, % a__2 form of glycogen synthase and cellular G6P level, it was concluded that the rate of glycogen synthesis and % a__- form of glycogen synthase are determined by intracellular G6P level. The stimulation of glycogen synthesis by fructose was shown to be due to the increase of G6P level, inhibiting G6Pase by accumulated F|P. These results suggest that perfused liver lost the mechanism which suppress G6Pase in vivo.
In regard to the mechanism, we thought the possibility that PPi-Ca works as an inhibitor of G6Pase, because in post-prandial state PPi is formed by UDPF-pyrophosphorylase reaction and activation of amino acids and fatty acids, and thus formed ppi which is a substrate of G6P translocase can penetrate to the lumen of ER where G6P phosphohydrolase and Ca are present. G6P phosphohydrolase can hydrolyze ppi but not Ca-PPi. Thus inhibition of G6Pase by Ca-PPi is highly possible. Although the accumulation of Ca-PPi in er is not shown yet, we succeeded to demonstrate the accumulation of Ca-PPi in perfused liver by the administration of acetate and two hormons, glucagon and adrenaline.
2. Purification of G6P translocase
We obtained partially purified G6P translocase preparation after solubilization by cholate and established the assay system by reconstitution using liposomes. We identified 55 KDa protein as G6P translocase on SDS-PAGE.
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Report
(3 results)
Research Products
(15 results)
