Institute for Clinical Chemistry, University Hospital and University of Zürich, Zürich, Switzerland.
Institute for Biochemistry, University of Zürich, Zürich, Switzerland.
Adv Exp Med Biol. 2022;1372:47-56. doi: 10.1007/978-981-19-0394-6_4.
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 C and C 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.
鞘脂类（SL）是一类化学多样性的脂质，在真核细胞中具有重要的结构和生理功能。SL 包含一个长链碱基（LCB）作为共同的结构元件，通常由 L-丝氨酸和长链酰基辅酶 A 的缩合形成。这种缩合是从头合成 SL 的第一步和限速步骤，由丝氨酸棕榈酰转移酶（SPT）催化。虽然棕榈酰-CoA 是首选底物，但 SPT 也可以代谢其他酰基辅酶 A，从而形成结构和功能各异的 LCB。哺乳动物 SPT 酶由三个核心亚基组成：SPTLC1、SPTLC2 和 SPTLC3。尽管 SPTLC1 和 SPTLC2 广泛表达，但 SPTLC3 的表达仅限于少数特定组织。SPTLC1 亚基是必需的，它可以与 SPTLC2 或 SPTLC3 结合形成活性酶。根据 SPTLC2 和 SPTLC3 亚基的比例，SPT 产物的谱发生变化。虽然 SPTLC1 和 SPTLC2 主要形成 C 和 C LCB，但 SPTLC1 和 SPTLC3 的组合产生了更广泛的 LCB 谱。基于遗传和人群的研究表明，SPTLC3 的表达和功能与改变的血浆 SL 谱和增加的心血管代谢疾病风险相关。动物和体外研究表明，SPTLC3 可能参与肝和心脏病理学，并可能成为这些疾病的治疗靶点。在这里，我们概述了 SPTLC3 在正常和病理条件下的作用的现有数据。
