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. In addition, 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
ApoA-V VLDL, HDL Metabolism of triglyceride rich lipoprotein 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 inhibition 8.76 11q23
ApoD HDL 4–7 CETP (CE transfer protein) activation 33 3q26.2
ApoE Chylomicron remnants, IDL HDL, LDL,VLDL 2-8 LDLr binding 34 19q13.2
ApoH Chylomicron, VLDL, LDL, HDL B2 glycoprotein 17q23
ApoJ HDL 10 Complement system 70 18p21
ApoL(1-6) HDL 43.9 22q12.3
ApoM HDL 25 66p21.3
Apo(a) Lp(a) 0–200 Plasminogen activation inhibition 250–800 6q27

Notes

  • ApoB-48 is exclusively found in chylomicrons. It is derived from the apoB-100 gene and is reduced to 48% of the N-terminal component of B-100 by RNA editing, with no LDL receptor (LDLr) binding domain.
  • ApoE is 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) is a distinguishing structural protein of lipoprotein(a). It is covalently bound to apoB-100 and inhibits plasminogen activation.

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).

References


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