1995 Fiscal Year Final Research Report Summary
Research for the Inhibitor of Cholesterol Biosynthesis with the aid of Morus alba Callus Cultures
| Project/Area Number |
06672116
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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 |
Chemical pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
NOMURA Taro Toho University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90057505)
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| Co-Investigator(Kenkyū-buntansha) |
HANO Yoshio Toho University, Faculty of Pharmaceutical Sciences, associate, prof., 薬学部, 助教授 (00156382)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Morus alba Callus Cultures / Isoprenoid Biosynthesis / HMG CoA reductase / Compactin / beta-Sitosterol / Isoprenylated phenol / Cholesterol / Hypercholesteremia |
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| Research Abstract |
Morus alba Cell cultures have at least two isoprenoid biosynthetic pathways, one of which is that for isoprenylated phenols and the other is that for sterols. In the administration of experiment with compactin, a potential 3-hydroxy 3-methylglutaryl CoA (HMG CoA) reductase inhibitor, to the M.alba cell cultures, the biosynthesis of the isoprene unit of the isoprenylated phenol was not affected by compactin, while the biosynthesis of the isoprene unit of beta-sitosterol from acetate was inhibited. This result suggests that compactin is a specific inhibitor of sterol biosynthesis from acetate origin. This work thus indicates the occurrence of at least two isoprenoid biosynthetic pathways, one of which is susceptible to compactin and the other resistant to compactin in M.alba cell cultures. In the previous experiment with [2-^<13>C] acetate, it has been found that the tricarboxylic acid (TCA) cycle participates in the biosynthesis of the isoprene unit of the isoprenylated phenol in M.alba cell cultures. In the administration of [2-^<13>C] acetic acid N-acetylcysteamine thioester to the cell cultures, the acetate precursor was intact into the isoprene unit of the isoprenylated phenol without the participation of the TCA cycle.
On the other hand, the isoprenylated phenols in the cell cultures are biosynthesized from cinnamoylpolyketide intermediate. Simultaneous administration of ^<13>C-labeled L-phenylalanine and L-tyrosine as well as administration of ^<13>-labeled cinnamic acid N-acetylcysteamine thioester derivative to the M.alba cell cultures gave a conclusive evidence for the two independent pathways leading to p-coumaroyl CoA.One is pathway from L-phenylalanine to p-coumaroyl CoA by way of cinnamoyl CoA and the other is pathway from L-tyrosine to p-coumaroyl CoA through the deamination reaction.
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