Lipoprotein lipase is active as a monomer

Anne P. Beigneux, Christopher M. Allan, Norma P. Sandoval, Geoffrey W. Cho, Patrick J. Heizer, Rachel S. Jung, Kimber L. Stanhope, Peter J. Havel, Gabriel Birrane, Muthuraman Meiyappan, John E. Gill Iv, Masami Murakami, Kazuya Miyashita, Katsuyuki Nakajima, Michael Ploug, Loren G. Fong, Stephen G. Young

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Lipoprotein lipase (LPL), the enzyme that hydrolyzes triglycerides in plasma lipoproteins, is assumed to be active only as a homodimer. In support of this idea, several groups have reported that the size of LPL, as measured by density gradient ultracentrifugation, is ∼110 kDa, twice the size of LPL monomers (∼55 kDa). Of note, however, in those studies the LPL had been incubated with heparin, a polyanionic substance that binds and stabilizes LPL. Here we revisited the assumption that LPL is active only as a homodimer. When freshly secreted human LPL (or purified preparations of LPL) was subjected to density gradient ultracentrifugation (in the absence of heparin), LPL mass and activity peaks exhibited the size expected of monomers (near the 66-kDa albumin standard). GPIHBP1-bound LPL also exhibited the size expected for a monomer. In the presence of heparin, LPL size increased, overlapping with a 97.2-kDa standard. We also used density gradient ultracentrifugation to characterize the LPL within the high-salt and low-salt peaks from a heparin- Sepharose column. The catalytically active LPL within the high-salt peak exhibited the size of monomers, whereas most of the inactive LPL in the low-salt peak was at the bottom of the tube (in aggregates). Consistent with those findings, the LPL in the low-salt peak, but not that in the high-salt peak, was easily detectable with single mAb sandwich ELISAs, in which LPL is captured and detected with the same antibody. We conclude that catalytically active LPL can exist in a monomeric state.

Original languageEnglish (US)
Pages (from-to)6319-6328
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jan 1 2019


  • Lipase
  • Lipolysis
  • Triglycerides

ASJC Scopus subject areas

  • General


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