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Biosynthetic Enzymes of Membrane Glycerophospholipid Diversity as Therapeutic Targets for Drug Development

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Druggable Lipid Signaling Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1274))

Abstract

Biophysical properties of membranes are dependent on their glycerophospholipid compositions. Lysophospholipid acyltransferases (LPLATs) selectively incorporate fatty chains into lysophospholipids to affect the fatty acid composition of membrane glycerophospholipids. Lysophosphatidic acid acyltransferases (LPAATs) of the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family incorporate fatty chains into phosphatidic acid during the de novo glycerophospholipid synthesis in the Kennedy pathway. Other LPLATs of both the AGPAT and the membrane bound O-acyltransferase (MBOAT) families further modify the fatty chain compositions of membrane glycerophospholipids in the remodeling pathway known as the Lands’ cycle. The LPLATs functioning in these pathways possess unique characteristics in terms of their biochemical activities, regulation of expressions, and functions in various biological contexts. Essential physiological functions for LPLATs have been revealed in studies using gene-deficient mice, and important roles for several enzymes are also indicated in human diseases where their mutation or dysregulation causes or contributes to the pathological condition. Now several LPLATs are emerging as attractive therapeutic targets, and further understanding of the mechanisms underlying their physiological and pathological roles will aid in the development of novel therapies to treat several diseases that involve altered glycerophospholipid metabolism.

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Acknowledgements

The Lipid Signaling Project, National Center for Global Health and Medicine receives funding from ONO Pharmaceuticals. This work was supported by AMED-CREST 19gm0910011 (to HS), AMED-P-CREATE 19 cm0106116 (to HS), AMED Program for Basic and Clinical Research on Hepatitis JP19fk0210041 (to HS).

Conflicts of Interest

The authors have no conflicts of interest affecting the objectivity of this review.

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Authors and Affiliations

  1. Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan

    William J. Valentine, Tomomi Hashidate–Yoshida, Shota Yamamoto & Hideo Shindou

  2. Department of Molecular Therapy, National Center of Neurology and Psychiatry, Tokyo, Japan

    William J. Valentine

  3. Department of Lipid Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hideo Shindou

  4. Japan Agency for Medical Research and Development, Tokyo, Japan

    Hideo Shindou

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  1. William J. Valentine
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  2. Tomomi Hashidate–Yoshida
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  3. Shota Yamamoto
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  4. Hideo Shindou
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Correspondence to William J. Valentine or Hideo Shindou .

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  1. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

    Yasuyuki Kihara

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Valentine, W.J., Hashidate–Yoshida, T., Yamamoto, S., Shindou, H. (2020). Biosynthetic Enzymes of Membrane Glycerophospholipid Diversity as Therapeutic Targets for Drug Development. In: Kihara, Y. (eds) Druggable Lipid Signaling Pathways. Advances in Experimental Medicine and Biology, vol 1274. Springer, Cham. https://doi.org/10.1007/978-3-030-50621-6_2

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