Lipid Metabolism & Physiology Flashcards

PCSK9 promotes LDL receptor degradation by which mechanism?

Answer: It binds LDLR extracellularly, causing lysosomal degradation of the receptor-LDL complex

PCSK9 binds to LDLR on the hepatocyte surface and redirects the receptor-LDL complex to lysosomal degradation instead of receptor recycling, reducing LDLR surface expression.

In familial hypercholesterolemia (FH), what is the most common molecular defect?

Answer: Loss-of-function mutation in the LDL receptor gene

The most common cause of FH is loss-of-function mutations in the LDLR gene, impairing LDL clearance and resulting in markedly elevated LDL-C from birth.

Sitosterolemia (phytosterolemia) results from mutations in which transporters?

Answer: ABCG5 and ABCG8

Loss-of-function mutations in ABCG5 or ABCG8 impair the secretion of plant sterols back into the intestinal lumen and bile, causing accumulation of sitosterol and other plant sterols in blood and tissues.

Which condition is characterized by extremely low or absent LDL-C due to a mutation in apolipoprotein B?

Answer: Abetalipoproteinemia and hypobetalipoproteinemia

Abetalipoproteinemia (MTP mutations) and familial hypobetalipoproteinemia (APOB mutations) both result in absent or markedly reduced ApoB-containing lipoprotein production and very low LDL-C.

The SREBP-2 transcription factor primarily regulates expression of genes involved in which pathway?

Answer: Cholesterol synthesis and LDL receptor expression

SREBP-2 (sterol regulatory element-binding protein 2) is activated when intracellular cholesterol is low, upregulating HMG-CoA reductase, LDLR, and other genes to restore cholesterol levels.

Hepatic lipase (HL) plays a role in converting which lipoprotein to another?

Answer: IDL to LDL and HDL2 to HDL3

Hepatic lipase hydrolyzes triglycerides and phospholipids in IDL (converting it to LDL) and in HDL2 (converting it to smaller, denser HDL3), playing a key role in both endogenous and reverse cholesterol transport pathways.

A patient has palmar xanthomas (xanthoma striata palmaris). Which lipid disorder is most characteristic of this finding?

Answer: Type III hyperlipidemia (dysbetalipoproteinemia)

Palmar (or planar) xanthomas in the skin creases of the palms are pathognomonic for type III hyperlipidemia (dysbetalipoproteinemia), caused by ApoE2/E2 genotype with IDL accumulation.