Structure of plasma sphingadienine

Renkonen, Ossi; Hirvisalo, E. L.

doi:10.1016/s0022-2275(20)43032-9

Cited by 54 publications

(19 citation statements)

References 16 publications

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“…3 C). This is likely due to the lack of a sphingadiene (L-18;2;2) long-chain base, which is known to have a second double bond in addition to the usual Δ4E double bond found in sphingosine 16 . However, we also find several sphinganine (L-18:0;2) lipids reduced, which have no double bond at all, e.g., most prominently SM 34:0;2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

A set of gene knockouts as a resource for global lipidomic changes

Spiegel

Lauber²,

Bachmann

et al. 2022

Sci Rep

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Enzyme specificity in lipid metabolic pathways often remains unresolved at the lipid species level, which is needed to link lipidomic molecular phenotypes with their protein counterparts to construct functional pathway maps. We created lipidomic profiles of 23 gene knockouts in a proof-of-concept study based on a CRISPR/Cas9 knockout screen in mammalian cells. This results in a lipidomic resource across 24 lipid classes. We highlight lipid species phenotypes of multiple knockout cell lines compared to a control, created by targeting the human safe-harbor locus AAVS1 using up to 1228 lipid species and subspecies, charting lipid metabolism at the molecular level. Lipid species changes are found in all knockout cell lines, however, some are most apparent on the lipid class level (e.g., SGMS1 and CEPT1), while others are most apparent on the fatty acid level (e.g., DECR2 and ACOT7). We find lipidomic phenotypes to be reproducible across different clones of the same knockout and we observed similar phenotypes when two enzymes that catalyze subsequent steps of the long-chain fatty acid elongation cycle were targeted.

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Section: Resultsmentioning

confidence: 99%

A set of gene knockouts as a resource for global lipidomic changes

Spiegel

Lauber²,

Bachmann

et al. 2022

Sci Rep

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“…In addition, two mammalian hydroxylated species of ceramides were studied: C18(2OH)-ceramide, (i.e., the [2 0 R]-isomer of the a-hydroxylated ceramide with a sphingosine long-chain base, and C16-phytoceramide with the [4 0 R]-hydroxysphinganine long-chain base (31,33,34,36,37)). Also the biologically potent metabolite ceramide-1-phosphate (38,39) (i.e., the product of ceramide kinase activity, and a ceramide containing a diunsaturated sphingadiene long-chain base [18:2 D4t,14c ], which is found in human plasma and aorta (40,41)), were included in this study. To compare the effect of the somewhat uncommon cis-double bond in the sphingadiene long-chain base with a cis-double bond at a comparable bilayer depth in the N-acyl chain, a ceramide with an unsaturated C18:1 D12c N-linked acyl chain was included in the study, although such a molecular species has not, according to the best of our knowledge, been reported among mammalian ceramide species.…”

Section: Introductionmentioning

confidence: 99%

Influence of Hydroxylation, Chain Length, and Chain Unsaturation on Bilayer Properties of Ceramides

Maula

Sazzad

Slotte

2015

Biophysical Journal

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Mammalian ceramides constitute a family of at least a few hundred closely related molecules distinguished by small structural differences, giving rise to individual molecular species that are expressed in distinct cellular compartments, or tissue types, in which they are believed to execute distinct functions. We have examined how specific structural details influence the bilayer properties of a selection of biologically relevant ceramides in mixed bilayers together with sphingomyelin, phosphatidylcholine, and cholesterol. The ceramide structure varied with regard to interfacial hydroxylation, the identity of the headgroup, the length of the N-acyl chain, and the position of cis-double bonds in the acyl chains. The interactions of the ceramides with sphingomyelin, their lateral segregation into ceramide-rich domains in phosphatidylcholine bilayers, and the effect of cholesterol on such domains were studied with DSC and various fluorescence-based approaches. The largest differences arose from the presence and relative position of cis-double bonds, causing destabilization of the ceramide's interactions and lateral packing relative to common saturated and hydroxylated species. Less variation was observed as a consequence of interfacial hydroxylation and the N-acyl chain length, although an additional hydroxyl in the sphingoid long-chain base slightly destabilized the ceramide's interactions and packing relative to a nonhydroxyceramide, whereas an additional hydroxyl in the N-acyl chain had the opposite effect. In conclusion, small structural details conferred variance in the bilayer behavior of ceramides, some causing more dramatic changes in the bilayer properties, whereas others imposed only fine adjustments in the interactions of ceramides with other membrane lipids, reflecting possible functional implications in distinct cell or tissue types.

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“…The extract was partitioned in the biphasic system chloro- form-methanol-water (8:4:3) (Folch et al, 1957) and the lipids were recovered from the lower layer. The glycerolipids were destroyed with mild alkaline methanolysis and unchanged ceramide hexosides together with sterol glucosides were then isolated from the methanolysates by column chromatography on silicic acid, as described previously (Renkonen and Hirvisalo, 1969). In addition to ceramide monohexosides small amounts of three slowly migrating glycolipids were revealed in this fraction with thin-layer chromatography (tic).…”

Section: Methodsmentioning

confidence: 99%