The unique role of apolipoprotein A-I in HDL remodeling and metabolism

Henry J. Pownall, Christian Ehnholm

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations


Purpose of review: To rationalize the distinctive biological behavior of apolipoprotein (apo)A-I and apoA-II in light of differences in their respective structures, properties, and physicochemical behavior. Recent findings: The distinctive metabolic behavior of apoA-I compared with that of apoA-II, which are revealed as differences in their interactions with the HDL receptor, scavenger receptor class B type I, can be understood in terms of their physico-chemical properties. Detergent and chaotropic perturbation of HDL unmasks properties that distinguish apoA-I from apoA-II and emulate the secondary effects of lecithin : cholesterol acyltransferase, cholesteryl ester transfer protein, and phospholipid transfer protein - the key protein factors in HDL remodeling, that is, formation of lipid-free apoA-I but not apoA-II and particle fusion. Thus, of the two major HDL apolipoproteins, apoA-I is the more plastic and labile and this difference gives apoA-I a unique physiological role that has been verified in mouse models of HDL metabolism. Summary: The compositions, structures, and properties of HDL particles are important determinants of the mechanisms by which these antiatherogenic lipoproteins are metabolized. Although the plasma lipid transfer proteins and lipid-modifying enzymes are important determinants of HDL processing, the distinctive structures and properties of apoA-I and apoA-II, the two major HDL proteins, determine in different ways the thermodynamic stability of HDL - the former through its greater plasticity and the latter by its higher lipophilicity. These distinctions have been revealed by physico-chemical studies of HDL stability in the context of numerous studies of enzyme and lipid transfer activities and of the interaction of HDL with its hepatic scavenger receptor.

Original languageEnglish (US)
Pages (from-to)209-213
Number of pages5
JournalCurrent opinion in lipidology
Issue number3
StatePublished - Jun 2006


  • Apolipoprotein
  • Atherosclerosis
  • Cholesterol transport
  • HDL
  • Lipid metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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