Biochemistry · Lipid Metabolism (Fatty Acid Synthesis and Oxidation, Lipoproteins, Cholesterol)

A patient has markedly elevated serum triglycerides with xanthomas, lipaemia retinalis, and recurrent pancreatitis. Genetic testing confirms homozygous lipoprotein lipase (LPL) deficiency (Fredrickson type I). The primary biochemical defect causing chylomicron accumulation is:

  • A Impaired VLDL synthesis by the liver
  • B Inability to hydrolyze chylomicron and VLDL triglycerides at the capillary endothelium
  • C Defective apo B-48 synthesis reducing chylomicron formation
  • D Overexpression of HMG-CoA reductase driving excess VLDL secretion
Correct answer: B. Inability to hydrolyze chylomicron and VLDL triglycerides at the capillary endothelium

Explanation

Lipoprotein lipase (LPL) is located on the luminal surface of capillary endothelium in muscle and adipose tissue, activated by apo C-II (on chylomicrons and VLDL). LPL hydrolyzes triglycerides in circulating chylomicrons and VLDL, releasing free fatty acids for tissue uptake. LPL deficiency (or apo C-II deficiency) prevents TG hydrolysis, causing massive chylomicron accumulation (type I hyperlipidemia). Serum is lactescent; risk of pancreatitis is high when TG > 1000 mg/dL. Treatment: strict fat restriction (<10–15% calories). It does not primarily affect HDL or LDL metabolism.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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