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.

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					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
ApoH	Chylomicron, VLDL, LDL, HDL					17q23
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