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Cited by 114Lipid Membrane Structure and BehaviorLipid metabolism and biosynthesisSphingolipid Metabolism and Signaling

Review of four major distinct types of human phospholipase A2

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Vasquez, Alexis M., Mouchlis, Varnavas D., Dennis, Edward A.·2018·Advances in Biological Regulation
DOI 10.1016/j.jbior.2017.10.009PMC PMC5807221
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Abstract

The phospholipase A 2 superfamily of enzymes plays a significant role in the development and progression of numerous inflammatory diseases. Through their catalytic action on membrane phospholipids, phospholipases are the upstream regulators of the eicosanoid pathway releasing free fatty acids for cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes which produce various well-known inflammatory mediators including leukotrienes, thromboxanes and prostaglandins. Elucidating the association of phospholipases A 2 with the membrane, the extraction and binding of phospholipid substrates, and their interactions with small-molecule inhibitors is crucial for the development of new anti-inflammatory therapeutics. Studying phospholipases has been challenging because they act on the surface of cellular membranes and micelles. Multidisciplinary approaches including hydrogen/deuterium exchange mass spectrometry, molecular dynamics simulations, and other computer-aided drug design techniques have been successfully employed by our laboratory to study interactions of phospholipases with membranes, phospholipid substrates and inhibitors. This review summarizes the application of these techniques to study four human recombinant phospholipases A 2.

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  • PLA2 consists of four major types: secretory PLA2 (sPLA2), cytosolic Ca2+-dependent PLA2 (cPLA2), Ca2+-independent PLA2 (iPLA2), and lipoprotein-associated PLA2 (lpPLA2).

    “PLA2 consists of four major types, secretory PLA2 (sPLA2), cytosolic Ca2+-dependent PLA2 (cPLA2) and Ca2+-independent PLA2 (iPLA2), and lipoprotein-associated PLA2 (lpPLA2) (27).”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [27]

    The Introduction (§1) identifies six major types of PLA2, including the four listed in the claim plus LPLA2 and AdPLA2. The paper reviews four types, but it does not say PLA2 consists of only those four. (LLM, conf=0.90)

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References 62 · Cited by 114

Research works printed but not linked: 60

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Authors
Vasquez, A. M., Mouchlis, V. D., & Dennis, E. A.
Affiliations
University of California San Diego (US)
Corresponding author
  • Mouchlis, Varnavas D.
  • Dennis, Edward A.
ORCID
Venue
Advances in Biological Regulation
Publisher
Elsevier BV
Published
2018-01
Volume
67
Pages
212-218
ISSN
2212-4926 (ISSN-L)
DOI
10.1016/j.jbior.2017.10.009
PMC
PMC5807221
OpenAlex
W2765607029
Cited by
114
References
62
Citations by year
2026: 3 · 2025: 13 · 2024: 8 · 2023: 25 · 2022: 10 · 2021: 8 · 2020: 16 · 2019: 20 · 2018: 11
FWCI
1.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Advances in Biological Regulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institutes of Health (GM20501-41)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
membrane binding, phospholipase inhibitors, eicosanoid pathway, inflammatory mediators, anti-inflammatory drug design, hydrogen-deuterium exchange mass spectrometry, molecular dynamics simulation, enzyme-membrane interaction
MeSH terms
Cell Membrane, Humans, Phospholipids, Mass Spectrometry, Deuterium Exchange Measurement, Phospholipases A2, Molecular Dynamics Simulation

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