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Sphingoid Base Diversity.

Thorsten Hornemann1

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Summary
This summary is machine-generated.

Minor sphingolipids (SLs) and their backbone structures (SPBs) are vital in cell functions. Dysregulation of SPB synthesis by serine palmitoyltransferase (SPT) subunits, like SPTLC3, links to neurotoxic and cardiometabolic diseases.

Keywords:
FADS3Long chain baseSPTLC3Serine-palmitoyltransferaseSphingoid baseSphingolipids

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolomics

Background:

  • Sphingolipids (SLs) are essential membrane components regulating diverse cellular processes.
  • Sphingoid bases (SPBs) form the structural backbone of all SLs, exhibiting heterogeneity in length and structure.
  • Understanding minor SPBs and their synthesis is crucial for cellular homeostasis.

Purpose of the Study:

  • To review the current understanding of minor sphingoid bases (SPBs).
  • To elucidate the role of serine palmitoyltransferase (SPT) subunits, particularly SPTLC3 and SPTSSA/B, in SPB formation.
  • To discuss the pathological implications of atypical SPBs in neurological and cardiometabolic diseases.

Main Methods:

  • Literature review focusing on sphingolipid metabolism and related enzymes.
  • Analysis of the role of SPT subunits in synthesizing structurally and metabolically distinct SPBs.
  • Examination of the association between atypical SPBs and diseases like HSAN1, diabetic neuropathy, obesity, and type 2 diabetes.

Main Results:

  • Minor SPBs, including neurotoxic 1-deoxysphingolipids (1-deoxySLs), are linked to neurological disorders.
  • Atypical SPBs, influenced by SPTLC3 induction, are implicated in the pathology of cardiometabolic conditions.
  • Alterations in SPB profiles contribute to disease progression in metabolic and neurodegenerative contexts.

Conclusions:

  • Understanding neglected aspects of sphingolipid metabolism, particularly minor SPBs, offers potential therapeutic targets.
  • Targeting SPT subunits involved in SPB synthesis could provide novel strategies for treating metabolic and neurodegenerative diseases.
  • Further research into sphingolipid metabolism is essential for developing new therapeutic interventions.