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Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases

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Sphingolipid Metabolism and Metabolic Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1372))

Abstract

Sphingolipids (SL) are a class of chemically diverse lipids that have important structural and physiological functions in eukaryotic cells. SL entail a long chain base (LCB) as the common structural element, which is typically formed by the condensation of l-serine and long chain acyl-CoA. This condensation is the first and the rate-limiting step in the de novo SL synthesis and catalyzed by the enzyme serine palmitoyltransferase (SPT). Although palmitoyl-CoA is the preferred substrate, SPT can also metabolize other acyl-CoAs, thereby forming a variety of LCBs, which differ in structures and functions. The mammalian SPT enzyme is composed of three core subunits: SPTLC1, SPTLC2, and SPTLC3. Whereas SPTLC1 and SPTLC2 are ubiquitously expressed, SPTLC3 expression is restricted to a few specific tissues. The SPTLC1 subunit is essential and can associate with either SPTLC2 or SPTLC3 to form an active enzyme. Depending on the stoichiometry of the SPTLC2 and SPTLC3 subunits, the spectrum of SPT products varies. While SPTLC1 and SPTLC2 primarily form C18 and C20 LCBs, the combination of SPTLC1 and SPTLC3 produces a broader spectrum of LCBs. Genetic and population based studies have shown that SPTLC3 expression and function are associated with an altered plasma SL profile and an increased risk for cardio-metabolic diseases. Animal and in vitro studies showed that SPTLC3 might be involved in hepatic and cardiac pathology and could be a therapeutic target for these conditions.

Here we present an overview of the current data on the role of SPTLC3 in normal and pathological conditions.

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Authors and Affiliations

  1. Institute for Clinical Chemistry, University Hospital and University of Zürich, Zürich, Switzerland

    Museer A. Lone & Thorsten Hornemann

  2. Institute for Biochemistry, University of Zürich, Zürich, Switzerland

    Florence Bourquin

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  1. Museer A. Lone
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  2. Florence Bourquin
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  3. Thorsten Hornemann
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Correspondence to Thorsten Hornemann .

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Editors and Affiliations

  1. Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA

    Xian-Cheng Jiang

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Lone, M.A., Bourquin, F., Hornemann, T. (2022). Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases. In: Jiang, XC. (eds) Sphingolipid Metabolism and Metabolic Disease. Advances in Experimental Medicine and Biology, vol 1372. Springer, Singapore. https://doi.org/10.1007/978-981-19-0394-6_4

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