Chemical Properties of Epidermal Lipids, Especially Sphingolipids, of the Antarctic Minke Whale

Yunoki, Keita; Ishikawa, Hajime; Fukui, Yutaka; Ohnishi, Masao

doi:10.1007/s11745-007-3145-2

Cited by 7 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent studies of a marine virus (Coccolithovirus) revealed that the viral genome contains a cluster of putative sphingolipid biosynthetic genes, including an SPT-like enzyme (23) that utilizes myristoyl-CoA and, therefore, generates C 16 -sphingoid bases when expressed in yeast. Sphingoid bases with 16 carbon atoms were also found in bovine milk (24,25) and as a part of the black epidermis from the Antarctic minke whale (26). A few earlier reports indicate the presence of C 16 -sphingoid bases in human plasma (27,28).…”

Section: Discussionmentioning

confidence: 94%

The SPTLC3 Subunit of Serine Palmitoyltransferase Generates Short Chain Sphingoid Bases

Hornemann

Penno

Rütti

et al. 2009

Journal of Biological Chemistry

152

118

View full text Add to dashboard Cite

The enzyme serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in the de novo synthesis of sphingolipids. Previously the mammalian SPT was described as a heterodimer composed of two subunits, SPTLC1 and SPTLC2. Recently we identified a novel third SPT subunit (SPTLC3). SPTLC3 shows about 68% identity to SPTLC2 and also includes a pyridoxal phosphate consensus motif. Here we report that the overexpression of SPTLC3 in HEK293 cells leads to the formation of two new sphingoid base metabolites, namely C 16 -sphinganine and C 16 -sphingosine. SPTLC3-expressing cells have higher in vitro SPT activities with lauryl-and myristoyl-CoA than SPTLC2-expressing cells, and SPTLC3 mRNA expression levels correlate closely with the C 16 -sphinganine synthesis rates in various human and murine cell lines. Approximately 15% of the total sphingolipids in human plasma contain a C 16 backbone and are found in the high density and low density but not the very low density lipoprotein fraction. In conclusion, we show that the SPTLC3 subunit generates C 16 -sphingoid bases and that sphingolipids with a C 16 backbone constitute a significant proportion of human plasma sphingolipids.Sphingolipids comprise a class of bioactive lipids that contribute to plasma membrane and plasma lipoprotein formation and exert a broad range of cellular signaling functions such as cell proliferation, endocytosis, and the response of cells to inflammatory and apoptotic stress signals (1-4).Sphingolipids are derived from the aliphatic amino alcohol sphingosine, which is formed from the precursors L-serine and palmitoyl-CoA. The condensation of serine with palmitoylCoA is catalyzed by the enzyme serine palmitoyltransferase (SPT) 3 (EC 2.3.1.50) and leads to the intermediate 3-ketodihydrosphingosine. 3-Ketodihydrosphingosine is then rapidly converted to dihydrosphingosine (sphinganine) and dihydroceramide. The desaturation of dihydroceramide generates ceramide, and the breakdown of ceramide by ceramidase finally forms sphingosine. The sphingosine backbone of ceramide is usually O-linked to a polar head group such as phosphocholine or carbohydrates and amide-linked to an acyl group. The combination of the sphingosine backbone with different head groups, in particular with various oligosaccharides, leads to a complex variety of different sphingolipid metabolites (5, 6). Moreover, it was shown recently that SPT is also able to use L-alanine as an alternative substrate, thereby generating the atypical sphingoid base 1-deoxysphinganine (7).SPT belongs to the family of pyridoxal phosphate-dependent ␣-oxoamine synthases. Other members of this family include 5-aminolevulinic acid synthase, 2-amino-3 ketobutyrate ligase, and 8-amino-7-oxononanoate synthase (8). SPT is ubiquitously expressed, and enzyme activity has been detected in all tissues tested so far including brain, lung, liver, kidney, and muscle (9). SPT is essential for embryonic development, and homozygous SPT knock-out mice are not viable (10). SPT has been believed to be a heterodimer compose...

show abstract

Section: Discussionmentioning

confidence: 94%

The SPTLC3 Subunit of Serine Palmitoyltransferase Generates Short Chain Sphingoid Bases

Hornemann

Penno

Rütti

et al. 2009

Journal of Biological Chemistry

152

118

View full text Add to dashboard Cite

show abstract

“…Milk gangliosides appear to contain the unusual sphingoid bases 3-ethoxy-d15:0, 3-ethoxy-d17:0, and 9-methyl-3-ethoxy-d15:0 (29). Sphingomyelin and cerebrosides in black epidermis from the Antarctic minke whale also have a high proportion (∼25%) of 16 carbon sphingoid bases (30). …”

Section: Diversity In the Sphingoid Base Backbones Of Sphingolipidsmentioning

confidence: 99%

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Pruett

Bushnev

Hagedorn

et al. 2008

Journal of Lipid Research

408

341

View full text Add to dashboard Cite

“Sphingosin” was first described by J. L. W. Thudichum in 1884 and structurally characterized as 2S,3R,4E-2-aminooctadec-4-ene-1,3-diol in 1947 by Herb Carter, who also proposed the designation of “lipides derived from sphingosine as sphingolipides.” This category of amino alcohols is now known to encompass hundreds of compounds that are referred to as sphingoid bases and sphingoid base-like compounds, which vary in chain length, number, position, and stereochemistry of double bonds, hydroxyl groups, and other functionalities. Some have especially intriguing features, such as the tail-to-tail combination of two sphingoid bases in the α,ω-sphingoids produced by sponges. Most of these compounds participate in cell structure and regulation, and some (such as the fumonisins) disrupt normal sphingolipid metabolism and cause plant and animal disease. Many of the naturally occurring and synthetic sphingoid bases are cytotoxic for cancer cells and pathogenic microorganisms or have other potentially useful bioactivities; hence, they offer promise as pharmaceutical leads. This thematic review gives an overview of the biodiversity of the backbones of sphingolipids and the broader field of naturally occurring and synthetic sphingoid base-like compounds.

show abstract

“…For example, the gangliosides of mammalian brain (33) and human gastrointestinal mucosa (34), as well as equine kidney sphingolipids (35), contain substantial amounts of C20-sphingoid bases. Shorter sphingoid bases can be found in relatively high amounts in, e.g., bovine sphingolipids (36)(37)(38) and the skin of the Antarctic minke whale (39), which contain sphingoid bases with 16 carbon atoms. Moreover, insect sphingolipids contain primarily shorter sphingoid bases (C14 and C16) (40,41).…”

Section: Introductionmentioning

confidence: 99%

Importance of the Sphingoid Base Length for the Membrane Properties of Ceramides

Maula

Artetxe

Grandell

et al. 2012

Biophysical Journal

View full text Add to dashboard Cite

The sphingoid bases of sphingolipids, including ceramides, can vary in length from 12 to >20 carbons. To study how such length variation affects the bilayer properties of ceramides, we synthesized ceramides consisting of a C12-, C14-, C16-, C18-, or C20-sphing-4-enin derivative coupled to palmitic acid. The ceramides were studied in mixtures with palmitoyloleoylphosphocholine (POPC) and/or palmitoylsphingomyelin (PSM), and in more complex bilayers also containing cholesterol. The trans-parinaric acid lifetimes showed that 12:1- and 14:1-PCer failed to increase the order of POPC bilayers, whereas 16:1-, 18:1-, and 20:1-PCer induced ordered- or gel-phase formation. Nevertheless, all of the analogs were able to thermally stabilize PSM, and a chain-length-dependent increase in the main phase transition temperature of equimolar PSM/Cer bilayers was revealed by differential scanning calorimetry. Similar thermal stabilization of PSM-rich domains by the ceramides was observed in POPC bilayers with a trans-parinaric acid-quenching assay. A cholestatrienol-quenching assay and sterol partitioning experiments showed that 18:1- and 20:1-PCer formed sterol-excluding gel phases with PSM, reducing the overall bilayer affinity of sterol. The effect of 16:1-PCer on sterol distribution was less dramatic, and no displacement of sterol from the PSM environment was observed with 12:1- and 14:1-PCer. The results are discussed in relation to other structural features that affect the bilayer properties of ceramides.

show abstract

Chemical Properties of Epidermal Lipids, Especially Sphingolipids, of the Antarctic Minke Whale

Cited by 7 publications

References 33 publications

The SPTLC3 Subunit of Serine Palmitoyltransferase Generates Short Chain Sphingoid Bases

The SPTLC3 Subunit of Serine Palmitoyltransferase Generates Short Chain Sphingoid Bases

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Importance of the Sphingoid Base Length for the Membrane Properties of Ceramides

Contact Info

Product

Resources

About