Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD

Acylcarnitines play an essential role in regulating the balance of intracellular sugar and lipid metabolism. They serve as carriers to transport activated long-chain fatty acids into mitochondria for β-oxidation as a major source of energy for cell activities. The liver is the most important organ for endogenous carnitine synthesis and metabolism. Hepatocellular carcinoma (HCC), a primary malignancy of the live with poor prognosis, may strongly influence the level of acylcarnitines. In this paper, the function, detection and alteration of acylcarnitine metabolism in HCC were briefly reviewed. An overview was provided to introduce the metabolic roles of acylcarnitines involved in fatty acid β-oxidation. Then different analytical platforms and methodologies were also briefly summarised. The relationship between HCC and acylcarnitine metabolism was described. Many of the studies reported that short, medium and long-chain acylcarnitines were altered in HCC patients. These findings presented current evidence in support of acylcarnitines as new candidate biomarkers for studies on the pathogenesis and development of HCC. Finally we discussed the challenges and perspectives of exploiting acylcarnitine metabolism and its related metabolic pathways as a target for HCC diagnosis and prognosis.

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Poor expression of long-chain noncoding RNA GAPLINC inhibits epithelial–mesenchymal transition, and invasion and migration of hepatocellular carcinoma cells

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000752 ◽

2019 ◽

Vol 30 (8) ◽

pp. 784-794 ◽

Cited By ~ 1

Author(s):

Weijia Zhang ◽

Hui Yao ◽

Yali Wu

Keyword(s):

Hepatocellular Carcinoma ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration ◽

Long Chain

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Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1516733112 ◽

2015 ◽

Vol 112 (42) ◽

pp. 12962-12967 ◽

Cited By ~ 31

Author(s):

Lihong Zhao ◽

Stefka Spassieva ◽

Kenneth Gable ◽

Sita D. Gupta ◽

Lan-Ying Shi ◽

...

Keyword(s):

Chain Length ◽

Small Subunit ◽

Fatty Acyl ◽

Substrate Affinity ◽

Serine Palmitoyltransferase ◽

Membrane Structures ◽

Long Chain Base ◽

Chain Lengths ◽

Long Chain

Sphingolipids typically have an 18-carbon (C18) sphingoid long chain base (LCB) backbone. Although sphingolipids with LCBs of other chain lengths have been identified, the functional significance of these low-abundance sphingolipids is unknown. The LCB chain length is determined by serine palmitoyltransferase (SPT) isoenzymes, which are trimeric proteins composed of two large subunits (SPTLC1 and SPTLC2 or SPTLC3) and a small subunit (SPTssa or SPTssb). Here we report the identification of an Sptssb mutation, Stellar (Stl), which increased the SPT affinity toward the C18 fatty acyl-CoA substrate by twofold and significantly elevated 20-carbon (C20) LCB production in the mutant mouse brain and eye, resulting in surprising neurodegenerative effects including aberrant membrane structures, accumulation of ubiquitinated proteins on membranes, and axon degeneration. Our work demonstrates that SPT small subunits play a major role in controlling SPT activity and substrate affinity, and in specifying sphingolipid LCB chain length in vivo. Moreover, our studies also suggest that excessive C20 LCBs or C20 LCB-containing sphingolipids impair protein homeostasis and neural functions.

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T1622 Hepatic Steatosis and Increase Risk of Hepatocellular Carcinoma in Mice Heterozygous for Long Chain 3-Hydorxy Acyl-CoA Dehydrogenase (LCHAD)

Gastroenterology ◽

10.1016/s0016-5085(09)63922-6 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-851

Author(s):

Raad S. Gitan ◽

Ghassan M. Hammoud ◽

Jerry J. Angdisen ◽

Alberto A. Diaz-Arias ◽

Jamal A. Ibdah

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Steatosis ◽

Increase Risk ◽

Long Chain

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Subunit composition of the mammalian serine-palmitoyltransferase defines the spectrum of straight and methyl-branched long-chain bases

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2002391117 ◽

2020 ◽

Vol 117 (27) ◽

pp. 15591-15598 ◽

Cited By ~ 3

Author(s):

Museer A. Lone ◽

Andreas J. Hülsmeier ◽

Essa M. Saied ◽

Gergely Karsai ◽

Christoph Arenz ◽

...

Keyword(s):

Enzyme Activity ◽

Mammalian Cells ◽

High Density Lipoproteins ◽

Serine Palmitoyltransferase ◽

Product Spectrum ◽

Long Chain Base ◽

The Individual ◽

And Function ◽

Long Chain

Sphingolipids (SLs) are chemically diverse lipids that have important structural and signaling functions within mammalian cells. SLs are commonly defined by the presence of a long-chain base (LCB) that is normally formed by the conjugation ofl-serine and palmitoyl-CoA. This pyridoxal 5-phosphate (PLP)-dependent reaction is mediated by the enzyme serine-palmitoyltransferase (SPT). However, SPT can also metabolize other acyl-CoAs, in the range of C14to C18, forming a variety of LCBs that differ by structure and function. Mammalian SPT consists of three core subunits: SPTLC1, SPTLC2, and SPTLC3. Whereas SPTLC1 and SPTLC2 are ubiquitously expressed, SPTLC3 expression is restricted to certain tissues only. The influence of the individual subunits on enzyme activity is not clear. Using cell models deficient in SPTLC1, SPTLC2, and SPTLC3, we investigated the role of each subunit on enzyme activity and the LCB product spectrum. We showed that SPTLC1 is essential for activity, whereas SPTLC2 and SPTLC3 are partly redundant but differ in their enzymatic properties. SPTLC1 in combination with SPTLC2 specifically formed C18, C19, and C20 LCBs while the combination of SPTLC1 and SPTLC3 yielded a broader product spectrum. We identifiedanteiso-branched-C18 SO (meC18SO) as the primary product of the SPTLC3 reaction. The meC18SO was synthesized fromanteiso-methyl-palmitate, in turn synthesized from a precursor metabolite generated in the isoleucine catabolic pathway. The meC18SO is metabolized to ceramides and complex SLs and is a constituent of human low- and high-density lipoproteins.

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