| Co-Investigator(Kenkyū-buntansha) |
MORISAKI Nobuhiro Chiba University, School of Medicine, Second Department of Internal Medicine, As, 医学部・内科学第二, 助手 (40174411)
SAITO Yasushi Chiba University, School of Medicine, Second Department of Internal Medicine, As, 医学部・内科学第二, 講師 (50101358)
KOBAYASHI Junji Chiba University, School of Medicine, Second Department of Internal Medicine, Re
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We found functionally deficient lipoprotein lipase in a patient of hyperchylomicronemia. To characterize this LpL and seek therapy for it, the following items were investigated.
1. Purified LpL from post-heparin plasma of hyperchylomicronemic patient, 14 years old girl, could not hydrolyze long chain fatty acid esters, but could hydrolyze short chain fatty acid ester, tributyrin. This enzyme did not bind to very low density lipoproteins. But, the LpL could hydrolyze lysolecithine- emulsified triolein, indicating that her LpL lacks interface recognition site, and that it might be recovered with some modification of the substrate lipoprotein particles.
2. Her Hypertriglyceride level was well control by administration of medium chain triglyceride(MCT). After MCT administration, triglyceride clearance was enhanced, and triolein-emulsified with MCT was hydrolyzed by patient's LpL almost as same as control LpL, indicating that MCT may modify the surface of lipoprotein such as the interaction with her LpL recovered.
3. To determine abnormal amino acid sequence of IRS deficient LpL, DNA of Exon 4 of LpL gene in which, catalytic center is supposed to exist, was sequenced, but no abnormality was observed, suggesting that catalytic site is intact, but IRS, which exists in another site, is wrong, and those sequences are under investigation.
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