The recovery of dysfunctional lipoprotein lipase (Asp204-Glu) activity by modification of substrate

• Published in: Atherosclerosis Vol. 183; no. 1; pp. 101 - 107
• Main Authors: Murano, Takeyoshi, Sako, Tamami, Oikawa, Shinichi, Shirai, Kohji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-11-2005; Elsevier
• Subjects: Adult; Amino Acid Substitution; Animals; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiolipins - pharmacology; Cardiology. Vascular system; Cardiovascular system; Cercopithecus aethiops; COS Cells; DNA Mutational Analysis; Emulsifying Agents - pharmacology; Exons - genetics; Functional defect; Fundamental and applied biological sciences. Psychology; General aspects; Humans; Hydrogen-Ion Concentration; Hydrolysis; Hyperlipoproteinemia Type IV - enzymology; Hyperlipoproteinemia Type IV - genetics; Lipoprotein lipase; Lipoprotein Lipase - deficiency; Lipoprotein Lipase - genetics; Lipoprotein Lipase - isolation & purification; Lipoprotein Lipase - metabolism; Lipoproteins, VLDL - metabolism; LPL (Asp204-Glu); Male; Medical sciences; Mutagenesis, Site-Directed; Mutation, Missense; Octoxynol; Pancreatitis - etiology; Pharmacology. Drug treatments; Phosphatidylcholines - pharmacology; Phosphatidylethanolamines - pharmacology; Phosphatidylserines - pharmacology; Point Mutation; Structure-Activity Relationship; Substrate condition; Substrate Specificity; Transfection; Triglycerides - metabolism; Triolein - metabolism; Vascular wall; Vertebrates: cardiovascular system; LPL (Asp204-Glu); Substrate condition; Lipoprotein lipase; Functional defect; Diphosphatidylglycerol; Phospholipid; Cardiovascular disease; Lipids; Esterases; Hyperlipoproteinemia; Anticoagulant; Lipoprotein; Enzymopathy; Vascular disease; Missense mutation; Atherosclerosis; Dyslipemia; Phosphatidylserine; Pancreatic disease; Human; Enzyme; Pancreatitis; Metabolic diseases; Deficiency lipoprotein lipase; Triglyceride; Carboxylic ester hydrolases; Genetic disease; Mutagenesis; Hypertriglyceridemia; Phosphatidylcholine; Digestive diseases; Glycosaminoglycan; Hydrolases; Heparin
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.02.025

Functional deficiency of lipoprotein lipase (LPL) was found in a patient with severe hypertriglyceridemia. The patient was 39-year-old man with a plasma triglyceride level of 2032
mg/dl, and suffered from recurrent pancreatitis. His post heparin plasma LPL mass was almost normal, but the LPL activity was remarkably decreased. Gene analysis showed that homozygote missense mutation (204 Asp (GA
C)-Glu (GA
G)) exists in exon 5 of LPL gene. The patient LPL purified from post heparin plasma scarcely hydrolyzed VLDL-triglyceride and also triolein emulsified with Triton X-100 or phosphatidylcholine. When phosphatidylethenolamine, phosphatidylserine and cardiolipin were used as an emulsifier for triolein, triolein-hydrolyzing activity of the patient's LPL was observed and was much higher than that of wild-type LPL. Mutant LPL gene (Asp204-Glu) was made by site-direct mutagenesis and was transfected to COS-1 cell. The expressed LPL (Asp204-Glu) also showed the same properties. These results suggested that the LPL (Asp204-Glu) is a functional deficiency, and the activity could be recovered by using acidic phospholipids as an emulsifier.