Sphingoid Base Diversity

Abstract

Sphingolipids (SL) are crucial components of cellular membranes and play pivotal roles in various biological processes, including cell growth, differentiation, apoptosis, and stress responses. All SL contain a sphingoid base (SPB) backbone which is the shared and class-defining element. SPBs are heterogeneous in length and structure. This review summarizes our current understanding on minor SPBs and the role of the serine palmitoyltransferase (SPT) in particular of its subunits SPTLC3 and SPTSSA/B in forming a spectrum of structurally and metabolically distinct SPBs. Some minor SPBs, such as 1-deoxysphingolipids (1-deoxySL) are neurotoxic and associated with neurological disorders such as hereditary sensory neuropathy type 1 (HSAN1) and diabetic neuropathy. Furthermore, the review discusses the pathological implications of atypical SPBs in cardiometabolic conditions such as obesity, type 2 diabetes or cardiomyopathy, where the induction of the SPTLC3 subunit alters the SPB profile and contributes to disease progression. Understanding these, often neglected aspects of the sphingolipid metabolism provides potential therapeutic targets for metabolic and neurodegenerative diseases, emphasizing the need for continued research in this area.

Keywords: FADS3; Long chain base; SPTLC3; Serine-palmitoyltransferase; Sphingoid base; Sphingolipids.