🐭 RAT series
Points to Ponder for NEET-PG, FMGE & NEXT
- LCAT deficiency disrupts cholesterol metabolism by preventing HDL maturation.
- LCAT deficiency leads to unesterified cholesterol accumulation and potentially corneal opacities, hemolytic anemia, and kidney disease.
- LCAT deficiency causes severely low HDL and elevated triglycerides on a lipid panel.
LCAT Deficiency
- LCAT Deficiency is a rare autosomal recessive disorder characterized by a deficiency in the enzyme Lecithin-cholesterol acyltransferase (LCAT). LCAT plays a critical role in cholesterol metabolism.
LCAT Function:
- Cholesterol exits cells as free cholesterol.
- The substrate for LCAT is HDL, which contains apo A-I, its most potent activator.
- LCAT esterifies free cholesterol on HDL (high-density lipoprotein), converting it to cholesterol ester.
- This esterification process allows HDL to mature and effectively transport cholesterol.
Pathophysiology:
- LCAT deficiency disrupts HDL maturation, leading to:
- Accumulation of unesterified cholesterol in tissues (e.g., cornea, kidneys).
- Rapid breakdown of HDL and its apolipoproteins (apoA-1, apoA-2).
- Predominance of nascent HDL (immature form) in circulation.
Laboratory Findings:
- Lipid panel:
- Severely low HDL cholesterol.
- Elevated VLDL (very-low-density lipoprotein) and triglycerides.
- High plasma unesterified cholesterol.
- Low plasma cholesterol ester.
Apolipoproteins:
- Play a crucial role in lipoprotein structure and function.
- Major HDL apolipoproteins: ApoA-1 and ApoA-2 (facilitate cholesterol efflux from cells).
- Main LDL (low-density lipoprotein) apolipoprotein: ApoB-100 (transports cholesterol to peripheral tissues).
- Also found in VLDL.
- Chylomicron apolipoprotein: ApoB-48 (truncated form synthesized in the intestine).
- ApoB-100 is synthesized in the liver.
- RNA editing process creates ApoB-48 by introducing a stop codon in the ApoB-100 mRNA transcript.
- Other apolipoproteins:
- ApoC-I, ApoC-II, ApoC-III: Smaller, transferable between lipoproteins.
- ApoE: Found in VLDL, HDL, chylomicrons, and remnants; facilitates remnant clearance by the liver.
