1-Deoxysphingolipids

Lone, Museer A.; Santos, T. C.; Alecu, Irina; Silva, Liana C.; Hornemann, Thorsten

doi:10.1016/j.bbalip.2018.12.013

Cited by 75 publications

(69 citation statements)

References 94 publications

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“…These sphingolipids form by the incorporation of alanine to palmitoyl‐CoA via serine palmitoyltransferase (Figure S2, Supporting Information). [ 23 ] Similar to sphinganine, deoxysphinganine can be acylated with fatty acids of various chain lengths giving rise to different species of deoxyceramides. However, due to the lack of the 1‐hydroxyl group, deoxyceramides cannot form complex sphingolipids or be degraded via the salvage pathway.…”

Section: Resultsmentioning

confidence: 99%

Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

2020

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Therapy-induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro-survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1-deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.

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Section: Resultsmentioning

confidence: 99%

Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

2020

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“…1-DeoxySLs are atypical SLs, which are generated from alanine instead of serine and involved in a variety of pathological conditions, including the rare hereditary sensory neuropathy type 1 (HSAN1) (2). Typically, LCBs present with a canonical ⌬4E double bond (DB).…”

Section: Sphingolipids (Sls)mentioning

confidence: 99%

FADS3 is a Δ14Z sphingoid base desaturase that contributes to gender differences in the human plasma sphingolipidome

Karsai

Lone

Kutalik

et al. 2020

Journal of Biological Chemistry

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Sphingolipids (SLs) are structurally diverse lipids that are defined by the presence of a long-chain base (LCB) backbone. Typically, LCBs contain a single Δ4E double bond (DB) (mostly d18:1), whereas the dienic LCB sphingadienine (d18:2) contains a second DB at the Δ14Z position. The enzyme introducing the Δ14Z DB is unknown. We analyzed the LCB plasma profile in a gender-, age-, and BMI-matched subgroup of the CoLaus cohort (n = 658). Sphingadienine levels showed a significant association with gender, being on average ∼30% higher in females. A genome-wide association study (GWAS) revealed variants in the fatty acid desaturase 3 (FADS3) gene to be significantly associated with the plasma d18:2/d18:1 ratio (p = −log 7.9). Metabolic labeling assays, FADS3 overexpression and knockdown approaches, and plasma LCB profiling in FADS3-deficient mice confirmed that FADS3 is a bona fide LCB desaturase and required for the introduction of the Δ14Z double bond. Moreover, we showed that FADS3 is required for the conversion of the atypical cytotoxic 1-deoxysphinganine (1-deoxySA, m18:0) to 1-deoxysphingosine (1-deoxySO, m18:1). HEK293 cells overexpressing FADS3 were more resistant to m18:0 toxicity than WT cells. In summary, using a combination of metabolic profiling and GWAS, we identified FADS3 to be essential for forming Δ14Z DB containing LCBs, such as d18:2 and m18:1. Our results unravel FADS3 as a Δ14Z LCB desaturase, thereby disclosing the last missing enzyme of the SL de novo synthesis pathway.

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“…This prevents its breakdown by S1P-lyase, meaning that deoxySLs cannot be terminally degraded by the canonical catabolic pathway [239]. A detailed overview on the metabolism and biological aspects of deoxySLs is described in a very recent review [244]. Herein, we briefly describe the biological, biophysical and pathological implications of DSB.…”

Section: Deoxy-sphingoid Basesmentioning

confidence: 99%

Mammalian sphingoid bases: Biophysical, physiological and pathological properties

Carreira

Santos

Lone

et al. 2019

Progress in Lipid Research

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Sphingoid bases encompass a group of long chain amino alcohols which form the essential structure of sphingolipids. Over the last years, these amphiphilic molecules were moving more and more into the focus of biomedical research due to their role as bioactive molecules. In fact, free sphingoid bases interact with specific receptors and target molecules and have been associated with numerous biological and physiological processes. In addition, they can modulate the biophysical properties of biological membranes. Several human diseases are related to pathological changes in the structure and metabolism of sphingoid bases. Yet, the mechanisms underlying their biological and pathophysiological actions remain elusive. Within this review, we aimed to summarize the current knowledge on the biochemical and biophysical properties of the most common sphingoid bases and to discuss their importance in health and disease.

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1-Deoxysphingolipids

Cited by 75 publications

References 94 publications

Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

FADS3 is a Δ14Z sphingoid base desaturase that contributes to gender differences in the human plasma sphingolipidome

Mammalian sphingoid bases: Biophysical, physiological and pathological properties

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