Plasma Lipid and Lipoproteins (VLDL, LDL, HDL)

Plasma lipoproteins
Lipids are mainly free cholesterol, cholesteryl ester, triglycerides and phospholipids, which exert crucial functions in humans:

Functions of lipids
Cholesterol and phospholipids: structural components of plasma membranes
Cholesterol: precursor of steroid hormones and bile acids
Triglycerides and free fatty acids: a major source of energy


Structure of lipoproteins
  • Lipids are transported in plasma within complex spherical particles called lipoproteins in which hydrophobic molecules (lipids) are associated with hydrophilic protein molecules, named apolipoproteins.
  • Apolipoproteins are structural components of lipoprotein particles (apo B, apo A-I, apo A-II), but they are also ligands for receptors on cell membranes (apo B, apo E), and can work as activators or inhibitors of key enzymes (apo A-I, apo C-II, apo C-III) or as activators or inhibitors of transport systems (apo A-IV, apo F).
  • Less hydrophobic components (free cholesterol, apolipoproteins and phospholipids) form the lipoprotein 'shell', while the most hydrophobic components (cholesteryl ester and triglycerides) form the 'core' of the particle.


Types of lipoproteins
Lipoproteins are divided into four broad classes:

Functions of lipids
Chylomicrons
  • normally detectable in plasma only in the postprandial state; are the largest particles
  • are mainly composed of triglycerides; their protein moiety comprises apo B48, apo A-I and apo C, with small amounts of apo A-II, apo A-IV and apo E
Very low-density lipoproteins (VLDLs)
  • are triglyceride-rich lipoproteins that circulate in plasma in the fasting state
  • intermediate-density lipoproteins (IDLs) show an intermediate composition between VLDL and IDL apolipoproteins are apo B100, apo Cs and apo E
LDLs
  • are smaller and heavier than VLDL since their protein-to-lipid ratio is higher
  • their apolipoproteins are apo B100 (95% of the proteins), apo Cs and apo E
  • note that each VLDL particle contains just one molecule of apo B100, located on the surface of the particle; when it is secreted by the liver, it retains this single apo B molecule in the downstream products of the lipolytic cascade (IDL and LDL)
High-density lipoproteins (HDLs)
  • are the smallest and heaviest lipoproteins
  • approximately 45% of their weight is made up of apolipoproteins, 65% of which is apo A-I, 10-25% apo A-II, 5-15% apo C, 1-3% apo E, plus trace amounts of apo A-IV

The four broad classes can be further divided into subclasses, on the basis of their density in preparative ultracentrifugation. The diameter, electrophoretic mobility and composition of the lipoproteins are given in Table 1.

Table 1. Characteristics and composition of plasma lipoproteins.


Lipid metabolism
Lipid metabolism follows two major pathways:
  • exogenous pathway occurring after fat absorption; and
  • endogenous pathway occurring in the postprandial state
Both pathways contribute to the lipoprotein levels in the fasting state.

The dyslipidaemias that have an important role in the pathogenesis of clinical atherosclerosis have been well defined in the fasting state. All lipoprotein classes, VLDL, LDL and HDL, are involved in different ways.

Peripheral lipoprotein transport
An overview of the interplay between the major lipoprotein classes is given in Figure 5. The physiological functions of this lipoprotein transport are two-fold:

  • It provides peripheral tissues with triglycerides as energy source.
  • It delivers cholesterol to peripheral cells as building blocks of cell membranes and to hepatocytes for elimination via the bile.
    • Triglycerides are assimilated by the tissues after lipolysis of the triglyceride-rich VLDL.
    • The cholesterol-rich LDL particles are taken up by the cells through the action of the LDL receptor and cholesterol becomes available to the cells after breakdown of the LDL molecule.
Figure 5. Overview of the interplay between the major lipopprotein classes.


Centripetal lipoprotein transport: reverse cholesterol transport
Cell cholesterol may be taken up by HDL particles, which then deliver the cholesterol to the liver. The cholesterol can then be excreted from the body after transformation to bile acids.



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