Apolipoprotein

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Apolipoproteins are lipid-binding proteins which are the constituents of the plasma lipoproteins, sub-microscopic spherical particles that transport dietary lipids through the bloodstream from the intestine to the liver, and endogenously synthesized lipids from the liver to tissues that can store them (adipocytes), metabolize them (muscle, heart, lung), or secrete them (breast).

The amphipathic (detergent-like) properties of apolipoproteins solubilize the hydrophobic lipid constituents of lipoproteins, but apolipoproteins also serve as enzyme co-factors, receptor ligands, and lipid transfer carriers that regulate the intravascular metabolism of lipoproteins and their ultimate tissue uptake.

Structure

Classification

Apolipoprotein Predominant lipoprotein Minor lipoproteins Plasma concentration (mg/dL) Role Molecular Weight (kDa) Chromosome
ApoA-I HDL Chylomicrons 90–160 LCAT activation 28.3 11q23
ApoA-II HDL Chylomicrons 25–45 Hepatic Lipase (HL) activation 17 1q21-23
ApoA-IV HDL 10-20 LCAT and Lipoprotein Lipase (LPL) activation 45 11q23
ApoB-48 Chylomicrons 0-100 Structural 241 2q23-24
ApoB-100 LDL, VLDL IDL, Lp(a) 50–150 LDLr binding 512 2q23–24
ApoC-I Chylomicrons, HDL IDL, VLDL 5–6 LCAT activation 6.63 19q13.2
ApoC-II Chylomicrons, VLDL HDL, IDL 3–5 LPL activation 8.84 19q13.2
ApoC-III Chylomicrons, VLDL HDL, IDL, LDL 10–14 LPL activation 8.76 11q23
ApoD HDL 4–7 CETP activation 33 3q26.2
ApoE Chylomicron remnants, IDL HDL, LDL,VLDL 2-8 LDLr binding 34 19q13.2
Apo(a) Lp(a) 0–200 Plasminogen activation inhibition 250–800 6q27

Metabolism

Apolipoprotein synthesis in the intestine is regulated principally by the fat content of the diet.

Apolipoprotein synthesis in the liver is controlled by a host of factors, including dietary composition, hormones (insulin, glucagon, thyroxin, estrogens, androgens), alcohol intake, and various drugs (statins, niacin,and fibric acids).

Role

  • ApoA-I: principal structural protein of HDL but also found in chylomicrons and activates lecithin:cholesterol acyltransferase (LCAT).
  • ApoA-II: another structural protein of HDL also found in chylomicrons and activates hepatic lipase (HL).
  • ApoA-IV: predominantly found in HDL and activates LCAT and lipoprotein lipase (LPL).
  • ApoB-48: exclusively found in chylomicrons, derived from the apoB-100 gene, and reduced to 48% of the N-terminal component of B-100 by RNA editing, with no LDL receptor (LDLr) binding domain.
  • ApoB-100: principal structural protein of LDL, alsofound in VLDL, IDL, and Lp(a); ligand for LDLr.
  • ApoC-I: primarily found in HDL and chylomicrons and also in IDL and VLDL and activates LCAT.
  • ApoC-II: protein primarily of VLDL and chylomicrons and also found in HDL and IDL and activates LPL.
  • ApoC-III: found broadly in HDL, IDL, LDL, VLDL, and chylomicrons but more consistently in VLDL and chylomicrons and inhibits LPL.
  • ApoD: exclusively found in HDL and possibly activates CE transfer protein (CETP).
  • ApoE: also found broadly in HDL, IDL, LDL, VLDL, and chylomicrons and binds to LDLr with varying affinity dependent on the inherited apoE allele. Three different apoE isoforms exist in humans: apoE2 with lower affinity to LDLr, apoE3 with intermediate binding affinity, and apoE4 with higher affinity.
  • Apo(a): distinguishing structural protein of Lp(a) that is covalently bound to apoB-100 and inhibits plasminogen activation

References


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