| Project/Area Number |
02671084
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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 |
内分泌・代謝学
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| Research Institution | Chiba University, School of Medicine |
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Principal Investigator |
SHIRAI Kohji School of Medicine, Second Department of Internal Medicine, Lecturer, 医学部・内科学第二講座, 講師 (00150269)
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| Co-Investigator(Kenkyū-buntansha) |
森崎 信尋 千葉大学, 医学部, 助手 (40174411)
SAITO Yasushi School of Medicine, Second Department of Internal Medicine, Lecturer, 医学部, 講師 (50101358)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Lipoprotein lipase / Chylomicronemia / Interface recognition site / LpL Gene / リポ蛋白リパ-ゼ(LPL) / LPL Gene |
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| Research Abstract |
We have found a hyperchylomicronemic patient with functionally deficient lipoprotein lipase(LPL) in which a function of lipid interface recognition site was supposed to be impaired. The patient's LPL hydrolyzed tributyrin, but not Triton X-100-emulsified triolein. However, it hydrolyzed triolein emulsified with lysolecithin. The structure of the interface recognition site of lipoprotein lipase was evaluated by analyzing the LPL gene of the patient's LPL.
Sequence analysis of the patient's DNA revealed a heterozygous nucleotide change : a C-G transversion at position of 1595, resulting in changing the codon for Ser 447 to a stop codon. Expression studies of this mutant LPL CDNA in Cos-I cells produced and secreted the LPL in the cultured media. The mutated LPL hydrolyzed much less Triton X-100-triolein than wild type LPL, whereas the hydrolysis of tributyrin and the hydrolysis. of triolein emulsified with lysolecithin were the same with both the mutant LPL and wild LPL.
These results suggested that this mutation might be responsible for the dysfunction of the patient's LPL having a defect in lipid interface recognition, and that C terminal 447 and 448 might be involved in the lipid interface recognition of the enzyme.
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