Comparative studies of vertebrate lipoprotein lipase: A key enzyme of very low density lipoprotein metabolism

Roger S. Holmes, John L. Vandeberg, Laura A. Cox

    Research output: Contribution to journalArticlepeer-review

    16 Scopus citations

    Abstract

    Lipoprotein lipase (LIPL or LPL; E.C.3.1.1.34) serves a dual function as a triglyceride lipase of circulating chylomicrons and very-low-density lipoproteins (VLDL) and facilitates receptor-mediated lipoprotein uptake into heart, muscle and adipose tissue. Comparative LPL amino acid sequences and protein structures and LPL gene locations were examined using data from several vertebrate genome projects. Mammalian LPL genes usually contained 9 coding exons on the positive strand. Vertebrate LPL sequences shared 58-99% identity as compared with 33-49% sequence identities with other vascular triglyceride lipases, hepatic lipase (HL) and endothelial lipase (EL). Two human LPL N-glycosylation sites were conserved among seven predicted sites for the vertebrate LPL sequences examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied. A CpG island was identified within the 5′-untranslated region of the human LPL gene which may contribute to the higher than average (×4.5 times) level of expression reported. Phylogenetic analyses examined the relationships and potential evolutionary origins of vertebrate lipase genes, LPL, LIPG (encoding EL) and LIPC (encoding HL) which suggested that these have been derived from gene duplication events of an ancestral neutral lipase gene, prior to the appearance of fish during vertebrate evolution. Comparative divergence rates for these vertebrate sequences indicated that LPL is evolving more slowly (2-3 times) than for LIPC and LIPG genes and proteins.

    Original languageEnglish (US)
    Pages (from-to)224-234
    Number of pages11
    JournalComparative Biochemistry and Physiology - Part D: Genomics and Proteomics
    Volume6
    Issue number2
    DOIs
    StatePublished - Jun 2011

    Keywords

    • Amino acid sequence
    • Evolution
    • Gene duplication
    • Lipoprotein lipase
    • Vertebrates

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology
    • Molecular Biology
    • Genetics

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