Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases

Tomomi, Narita; Naganuma, Tatsuro; Sase, Yurie; Kihara, Akio

doi:10.1038/srep25469

Cited by 27 publications

(21 citation statements)

References 49 publications

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“…Dietary SM, in particular, is known to dose-dependently reduce the intestinal absorption of cholesterol, TG, and fatty acids in rodents [10]. Products of SM digestion, such as ceramides and sphingosine, also inhibit cholesterol and fatty acid absorption [59][60][61]. Compared to SM derived from egg yolk, SM from milk has been shown to have stronger effects on inhibiting the intestinal absorption of fat and cholesterol in rats, potentially due to stronger hydrophobic interactions between milk SM and other lipids [62].…”

Section: Effects On Intestinal Lipid Absorptionmentioning

confidence: 99%

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Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

et al. 2020

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Milk fat is encased in a polar lipid-containing tri-layer milk fat globule membrane (MFGM), composed of phospholipids (PLs) and sphingolipids (SLs). Milk PLs and SLs comprise about 1% of total milk lipids. The surfactant properties of PLs are important for dairy products; however, dairy products vary considerably in their polar lipid to total lipid content due to the existence of dairy foods with different fat content. Recent basic science and clinical research examining food sources and health effects of milk polar lipids suggest they may beneficially influence dysfunctional lipid metabolism, gut dysbiosis, inflammation, cardiovascular disease, gut health, and neurodevelopment. However, more research is warranted in clinical studies to confirm these effects in humans. Overall, there are a number of potential effects of consuming milk polar lipids, and they should be considered as food matrix factors that may directly confer health benefits and/or impact effects of other dietary lipids, with implications for full-fat vs. reduced-fat dairy.

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Section: Effects On Intestinal Lipid Absorptionmentioning

confidence: 99%

“…In vitro studies suggest that SM in mixed micelles can reduce TG hydrolysis by inhibiting human pancreatic lipase-colipase activity [65,66]. Long-chain bases of SLs and long-chain fatty acids also have been reported to compete with each other for cellular uptake, since they both utilize acyl-CoA synthetases [61].…”

Section: Effects On Intestinal Lipid Absorptionmentioning

confidence: 99%

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

et al. 2020

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“…We recently revealed the FA transporter family (also known as acyl-CoA synthetase family) members Faa1 and Faa4 are involved in importing both LCBs and long-chain FAs (30). We found here that Rsb1 facilitated export of DHS and 1-hexadecanol, but not palmitic acid (Fig.…”

Section: Discussionmentioning

confidence: 68%

Loop 5 region is important for the activity of the long-chain base transporter Rsb1

2016

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Intracellular lipid amounts are regulated not only by metabolism but also by efflux. Yeast Rsb1 is the only known transporter/floppase of the sphingolipid components long-chain bases (LCBs). However, even fundamental knowledge about Rsb1, such as important amino acid residues for activity and substrate recognition, still remains unclear. Rsb1 belongs to the Rta1-like family. To date, it has not been determined whether all family members share a common ability to export LCBs. Here, we revealed that within the Rta1-like family, only Rsb1 suppressed the hypersensitivity of the mutant cells lacking LCB 1-phoshate-degrading enzymes, suggesting that LCB-exporting activity is specific to Rsb1. Rsb1 contains a characteristic region (loop 5), which does not exist in other proteins of the Rta1-like family. We found that deletion of this region caused loss of Rsb1 function. Further mutational analysis of loop 5 revealed that the charged amino acid residues E223, D225 and R236 were important for Rsb1 activity. In addition to LCBs, Rsb1 facilitated the export of 1-hexadecanol, but not palmitic acid, which suggests that Rsb1 recognizes the C1 hydroxyl group. Thus, our findings provide an important clue for understanding the molecular mechanism of LCB export.

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“…and Faa4 (7,37). We found that an exogenous supply of sphingosine, a major LCB in mammals, can also rescue the growth of…”

Section: E Effect Of Remodeling Of the Structure Of Longchain Bases mentioning

confidence: 77%

Structure–Function Relationship of Complex Sphingolipids in Yeast

Tani

2016

Trends in Glycoscience and Glycotechnology

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Complex sphingolipids are major components of eukaryotic membranes and play critical roles in many physiologically important events. In mammals, complex glycosphingolipids can carry hundreds of sugar chains as polar head groups, and this structural diversity and complexity is thought to be closely related to their multiple biological functions. In the budding yeast Saccharomyces cerevisiae, the complex sphingolipids have five types of ceramide differing in hydroxylation status, and three types of polar head group containing inositol phosphate and mannose, and thus S. cerevisiae complex sphingolipids can be classified into 15 subtypes in total. Due to the limited molecular classes, the structural diversity of sphingolipids in S. cerevisiae is relatively simple as compared with that in mammalian cells. In S. cerevisiae, depletion of all complex sphingolipids causes a strong growth defect. In contrast, addition of hydroxyl groups to the ceramide moiety in complex sphingolipids and extension of the polar head group are non-essential for growth. However, recent studies indicated that these structural modifications of complex sphingolipids are important for many cellular functions. This review focuses on the physiological importance of each detailed structure and the structural diversity of complex sphingolipids in S. cerevisiae and the other yeasts.

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Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases

Cited by 27 publications

References 49 publications

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

Loop 5 region is important for the activity of the long-chain base transporter Rsb1

Structure–Function Relationship of Complex Sphingolipids in Yeast

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