Lipoprotein Functions Overview

Lipoproteins are composed of varying proportions of proteins, cholesterol, TGs, and phospholipids. LDL and HDL carry the most cholesterol. Cholesterol is needed to maintain cell membrane integrity and synthesize bile acids, steroids, and vitamin D.

Chylomicron

Delivers dietary TGs to peripheral tissues. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. Secreted by intestinal epithelial cells.

VLDL (Very Low-Density Lipoprotein)

Delivers hepatic TGs to peripheral tissue. Secreted by liver.

Lipoprotein Functions: IDL, LDL, and HDL

IDL (Intermediate-Density Lipoprotein)

Delivers TGs and cholesterol to liver. Formed from degradation of VLDL.

LDL (Low-Density Lipoprotein)

Delivers hepatic cholesterol to peripheral tissues. Formed by hepatic lipase modification of IDL in the liver and peripheral tissue. Taken up by target cells via receptor-mediated endocytosis. LDL is lethal.

HDL (High-Density Lipoprotein)

Mediates reverse cholesterol transport from peripheral tissues to liver. Acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism). Secreted from both liver and intestine. Alcohol ↑ synthesis. HDL is Healthy.

Abetalipoproteinemia

Autosomal recessive. Mutation in gene that encodes microsomal transfer protein (MTP). Chylomicrons, VLDL, LDL absent. Deficiency in apo B₄₈– and apo B₁₀₀-containing lipoproteins. Affected infants present with severe fat malabsorption, steatorrhea, failure to thrive. Later manifestations include retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, acanthocytosis. Intestinal biopsy shows lipid-laden enterocytes #boundingbox.

Treatment: restriction of long-chain fatty acids, large doses of oral vitamin E.

Familial Dyslipidemias: Types I & II

Type I—Hyperchylomicronemia

• Inheritance: AR (Autosomal Recessive)
• Pathogenesis: Lipoprotein lipase or apo CII deficiency
• ↑ Blood Level: Chylomicrons, TG, cholesterol
• Clinical: Pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas (no ↑ risk for atherosclerosis). Creamy layer in supernatant.

Type II—Hypercholesterolemia

• Inheritance: AD (Autosomal Dominant)
• Pathogenesis: Absent or defective LDL receptors, or defective apo B₁₀₀
• ↑ Blood Level: IIa: LDL, cholesterol; IIb: LDL, cholesterol, VLDL
• Clinical: Heterozygotes (1:500) have cholesterol ≈ 300 mg/dL; homozygotes (very rare) have cholesterol ≥ 700 mg/dL. Accelerated atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus.

Familial Dyslipidemias: Types III & IV

Type III—Dysbetalipoproteinemia

• Inheritance: AR (Autosomal Recessive)
• Pathogenesis: ApoE (defective in type three)
• ↑ Blood Level: Chylomicrons, VLDL
• Clinical: Premature atherosclerosis, tuberoeruptive and palmar xanthomas.

Type IV—Hypertriglyceridemia

• Inheritance: AD (Autosomal Dominant)
• Pathogenesis: Hepatic overproduction of VLDL
• ↑ Blood Level: VLDL, TG
• Clinical: Hypertriglyceridemia (> 1000 mg/dL) can cause acute pancreatitis. Related to insulin resistance.

Topics Covered:

• Lipoprotein Functions: Chylomicron & VLDL
• Lipoprotein Functions: IDL, LDL, HDL
• Abetalipoproteinemia
• Familial Dyslipidemias: Hyperchylomicronemia & Hypercholesterolemia
• Familial Dyslipidemias: Dysbetalipoproteinemia & Hypertriglyceridemia