Harvey's Garden

Lipid transport

3 min read

See also Lipid-lowering agents

Key Points

  • TG
    • Energy reserve
    • Synthesized in liver and adipocytes
    • Stored in adipocytes
  • Cholesterol
    • Incorporated in all cell membranes in the lipid bilayer: increases membrane fluidity and stability
    • Precursor for synthesis of:
      • Steroid hormones (e.g., androgens, estrogens, mineralocorticoids, glucocorticoids)
      • Bile acids
      • Vitamin D
    • Transport in blood via lipoproteins
      • From the intestine to the liver: together with TAGs in chylomicrons
      • From the liver to peripheral tissues: via VLDL and LDL
      • From peripheral tissues to the liver (reverse cholesterol transport): via HDL and IDL
  • HDL
    • Transport cholesterol from peripheral tissues (e.g., atherosclerotic arteries) to the liver (reverse cholesterol transport), where it is excreted (e.g., via bile)
  • LDL
    • Transport cholesterol from the liver to peripheral tissues and arteries
  • VLDL
    • Transport hepatic triglycerides from the liver to peripheral tissues
  • Chylomicron
    • Secreted by the intestinal epithelial cells into lymphatics
    • Transport dietary triglycerides from the intestine to peripheral tissues

Lipoproteins (HDL, VLDL, LDL)

  • Protein is denser than fat.
  • Therefore, the higher the ratio of protein to fat, the higher the density of the lipoprotein particle.
    • VLDL: ~0.98 g/mL (high TG, to adipocytes)
    • IDL: ~1.0 g/mL (“intermediate” means an intermediate step between VLDL and LDL, not intermediate density)
    • LDL: ~1.04 g/mL (high cholesterol, to peripheral cells)
    • HDL: ~1.12 g/mL

I. Lipid Synthesis

This primarily occurs in the liver in the well-fed state (stimulated by insulin).

A. Fatty Acid Synthesis

  • Location: Cytoplasm.
  • Substrate: Acetyl-CoA (transported from mitochondria via the citrate shuttle).
  • Rate-Limiting Enzyme: Acetyl-CoA Carboxylase (ACC). It converts acetyl-CoA to malonyl-CoA and requires biotin (vitamin B7).
    • Activation: Insulin, Citrate.
    • Inhibition: Glucagon, Palmitoyl-CoA.
  • Key Enzyme Complex: Fatty Acid Synthase. It uses malonyl-CoA and requires NADPH to produce palmitate (a 16-carbon fatty acid).

B. Cholesterol Synthesis

  • Location: Cytoplasm and smooth endoplasmic reticulum.
  • Substrate: Acetyl-CoA.
  • Rate-Limiting Enzyme: HMG-CoA Reductase. It converts HMG-CoA to mevalonate.
    • Inhibition: High cholesterol levels, Glucagon. Statins are competitive inhibitors of this enzyme.
    • Activation: Insulin.

II. Lipid Transport via Lipoproteins

Lipids are transported in the blood as lipoproteins, which consist of a lipid core and an outer shell of apolipoproteins and phospholipids.

Key Apolipoproteins

  • ApoA-I: Activates LCAT for HDL maturation. Found on HDL.
  • ApoB-48: Mediates chylomicron secretion from enterocytes.
  • ApoB-100: Binds to the LDL receptor for uptake. Found on VLDL, IDL, and LDL.
  • ApoC-II: Activates lipoprotein lipase (LPL) to break down triglycerides.
  • ApoE: Mediates remnant uptake by the liver.

Transport Pathways

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Exogenous Pathway: Transport of Dietary Lipids

Endogenous Pathway: Transport of Endogenously Synthesized Lipids

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  1. Exogenous Pathway (Dietary Fat)

    • Chylomicrons are created in the intestine (containing ApoB-48) to transport dietary triglycerides.
    • In the blood, they acquire ApoC-II and ApoE from HDL.
    • Lipoprotein Lipase (LPL), activated by ApoC-II, cleaves triglycerides, releasing fatty acids to peripheral tissues.
    • Chylomicron remnants (rich in cholesterol) are cleared by the liver via ApoE.

  2. Endogenous Pathway (Liver-Synthesized Fat)

    • VLDL is created in the liver (containing ApoB-100) to transport endogenous triglycerides.
    • LPL degrades triglycerides in VLDL, forming IDL (VLDL remnant).
    • IDL can be cleared by the liver or further processed by hepatic lipase into LDL.
    • LDL (“bad cholesterol”) delivers cholesterol to peripheral tissues via LDL receptors that recognize ApoB-100.

  3. Reverse Cholesterol Transport

    • HDL (“good cholesterol”) is secreted by the liver and intestine (containing ApoA-I).
    • It picks up excess cholesterol from peripheral tissues.
    • LCAT (activated by ApoA-I) esterifies the cholesterol, trapping it in the HDL core.
    • HDL returns the cholesterol to the liver for excretion in bile.

Common steps for exo and endo pathways: bind to HDL, deliver TG to adipocytes, bind to ApoE receptor and cleared by hepatic lipase

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