Lipoprotein Metabolism & Hyperlipidemias
| Apolipoprotein / Enzyme | Primary Location | High-Yield Biochemical Function |
|---|---|---|
| Apo B-48 | Chylomicrons, Remnants | Mediates chylomicron secretion from enterocytes into lymphatics. Lacks the LDL-receptor binding domain. |
| Apo B-100 | VLDL, IDL, LDL | Mediates hepatic secretion of VLDL. Acts as the primary structural ligand for the LDL Receptor. |
| Apo C-II | Chylomicrons, VLDL, HDL | An essential cofactor that activates Lipoprotein Lipase (LPL) to hydrolyze core triglycerides. |
| Apo E | All except LDL | Mediates remnant uptake by driving binding to hepatic LRP and LDL receptors. |
| Apo A-I | HDL | Activates LCAT (Lecithin-cholesterol acyltransferase) to esterify cholesterol for reverse transport. |
| CETP | Plasma Shunt Protein | Mediates transfer of cholesteryl esters from HDL to VLDL/IDL/LDL in exchange for triglycerides. |
| PCSK9 | Hepatic Extracellular | Binds to the LDL receptor and targets it for lysosomal degradation, reducing clearance. |
High-Yield Familial Dyslipidemias:
- Type I – Familial Chylomicronemia: Autosomal recessive deficiency in LPL or Apo C-II. Chylomicrons build up, driving sky-high plasma triglycerides. Presents with recurrent eruptive xanthomas, milky plasma, and acute pancreatitis. No increased risk for atherosclerosis.
- Type IIa – Familial Hypercholesterolemia: Autosomal dominant defect or absence of functional LDL Receptors or mutant Apo B-100. Serum LDL levels skyrocket. Presents with premature coronary artery disease, tendon xanthomas (Achilles), and corneal arcus.
- Type III – Familial Dysbetalipoproteinemia: Patient is homozygous for the Apo E2 isoform, which binds poorly to hepatic receptors. Chylomicron remnants and IDL accumulate in circulation. Key markers: palmar xanthomas and premature cardiovascular disease.
- Abetalipoproteinemia Pathology: Autosomal recessive loss-of-function mutation in the Microsomal Triglyceride Transfer Protein (MTP). Enterocytes cannot load Apo B-48 and hepatocytes cannot load Apo B-100. Chylomicrons and VLDL are completely absent from plasma. Biopsy shows enterocytes packed with lipids; clinically presents with malabsorption, steatorrhea, acanthocytosis (spur cells), and retinitis pigmentosa.