Sites of HDL (high-density lipoprotein) biogenesis In human lipoprotein metabolism, where are nascent HDLs synthesized before they mature in plasma?

Introduction / Context:
High density lipoproteins (HDLs) mediate reverse cholesterol transport, shuttling excess cholesterol from peripheral tissues to the liver. Understanding where HDLs originate helps explain clinical biomarkers such as HDL cholesterol and the actions of apolipoproteins like ApoA I.

Given Data / Assumptions:

• HDL particles begin as small, discoidal, protein rich particles.
• ApoA I is the signature apolipoprotein of HDL.
• Plasma enzymes (LCAT) and transporters (ABCA1, ABCG1) remodel HDLs after secretion.

Concept / Approach:

Nascent HDLs are synthesized and secreted primarily by hepatocytes (liver) and enterocytes (intestine). These tissues produce ApoA I and other components. Once in plasma, interactions with ABCA1 on peripheral cells load free cholesterol and phospholipid onto ApoA I to form discoidal HDL, which is then esterified by LCAT into cholesteryl esters, generating spherical HDL that can exchange lipids via CETP and deliver cholesterol to the liver via SR B1.

Step-by-Step Solution:

Verification / Alternative check:

Tracer studies and gene expression data show high ApoA I production in liver and intestine; genetic defects in ABCA1 cause Tangier disease with near absence of HDL, supporting the biogenesis pathway.

Why Other Options Are Wrong:

Blood is the conduit, not the site of synthesis; particles are cell derived. Pancreas and kidney are not primary HDL synthetic organs. Adipose tissue contributes lipids but does not synthesize nascent HDL as the main source.

Common Pitfalls:

Assuming HDL forms spontaneously in plasma without cellular origin or confusing HDL origin with chylomicron origin (intestine only).

Final Answer:

Liver and intestine (both tissues)