ESFINGOLIPIDOS PDF

Abstract Sphingolipids in biological membranes have attracted a renewed interest in the last decades because of their remarkable biological effects, namely their capacity to act as metabolic signals in a variety of regulatory cascades. Sphingolipids exhibit special affinities towards other lipids, and in some cases they can induce lateral phase segregation and membrane heterogeneities. Thus lipid-lipid interactions involving bioactive sphingolipids, such as ceramides, have become increasingly relevant. This review focuses on the recent studies in the field, and how simple bioactive sphingolipids can modulate the biophysical properties of membranes through lipid-lipid interactions, either between them or with other lipids such as common phospholipids or cholesterol. Todos ellos se denominan colectivamente como esfingoides. Fig 1.

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Structure[ edit ] The long-chain bases, sometimes simply known as sphingoid bases, are the first non-transient products of de novo sphingolipid synthesis in both yeast and mammals. These compounds, specifically known as phytosphingosine and dihydrosphingosine also known as sphinganine, [2] although this term is less common , are mainly C18 compounds, with somewhat lower levels of C20 bases.

Sphingoid bases are the fundamental building blocks of all sphingolipids. The main mammalian sphingoid bases are dihydrosphingosine and sphingosine, while dihydrosphingosine and phytosphingosine are the principle sphingoid bases in yeast. Ceramides , as a general class, are N-acylated sphingoid bases lacking additional head groups. Dihydroceramide is produced by N-acylation of dihydrosphingosine.

Dihydroceramide is found in both yeast and mammalian systems. Ceramide is produced in mammalian systems by desaturation of dihydroceramide by dihydroceramide desaturase 1 DES1.

This highly bioactive molecule may also be phosphorylated to form ceramidephosphate. Phytoceramide is produced in yeast by hydroxylation of dihydroceramide at C Complex sphingolipids may be formed by addition of head groups to ceramide or phytoceramide: Sphingomyelins have a phosphocholine or phosphoethanolamine molecule with an ester linkage to the 1-hydroxy group of a ceramide.

Cerebrosides have a single glucose or galactose at the 1-hydroxy position. Sulfatides are sulfated cerebrosides. Gangliosides have at least three sugars, one of which must be sialic acid. Inositol -containing ceramides, which are derived from phytoceramide, are produced in yeast. These include inositol phosphorylceramide, mannose inositol phosphorylceramide, and mannose diinositol phosphorylceramide. Mammalian sphingolipid metabolism[ edit ] De novo sphingolipid synthesis begins with formation of 3-keto-dihydrosphingosine by serine palmitoyltransferase.

However, studies have demonstrated that serine palmitoyltransferase has some activity toward other species of fatty acyl-CoA [8] and alternative amino acids , [9] and the diversity of sphingoid bases has recently been reviewed. Dihydrosphingosine is acylated by a dihydro -ceramide synthase, such as Lass1p or Lass2p also termed as CerS , to form dihydroceramide.

Sphingolipidoses are labeled at corresponding stages that are deficient. Ceramide may subsequently have several fates. It may be phosphorylated by ceramide kinase to form ceramidephosphate.

Alternatively, it may be glycosylated by glucosylceramide synthase or galactosylceramide synthase. Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase. Diacylglycerol is generated by this process. Finally, ceramide may be broken down by a ceramidase to form sphingosine.

Sphingosine may be phosphorylated to form sphingosinephosphate. This may be dephosphorylated to reform sphingosine. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide.

Similarly, sphingomyelin may be broken down by sphingomyelinase to form ceramide. This forms ethanolamine phosphate and hexadecenal. Certain complex glycosphingolipids were found to be involved in specific functions, such as cell recognition and signaling. Cell recognition depends mainly on the physical properties of the sphingolipids, whereas signaling involves specific interactions of the glycan structures of glycosphingolipids with similar lipids present on neighboring cells or with proteins.

These sphingolipid-based microdomains, or " lipid rafts " were originally proposed to sort membrane proteins along the cellular pathways of membrane transport. At present, most research focuses on the organizing function during signal transduction. Sphingolipids are virtually absent from mitochondria and the ER , but constitute a molar fraction of plasma membrane lipids. Bacteria that do produce sphingolipids are found in family Sphingomonadaceae , the FCB group some members , and some parts of Deltaproteobacteria.

These single-celled organisms are often more genetically tractable than mammalian cells, and strain libraries are available to supply strains harboring almost any non-lethal open reading frame single deletion. The two most commonly used yeasts are Saccharomyces cerevisiae and Schizosaccharomyces pombe , although research is also done in the pathogenic yeast Candida albicans. These effects include regulation of endocytosis , ubiquitin-dependent proteolysis and, thus, regulation of nutrient uptake [26] , cytoskeletal dynamics, the cell cycle , translation , posttranslational protein modification, and the heat stress response.

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Sphingolipide

En las posiciones 4 o 6 pueden tener grupos hidroxilos y dobles enlaces en otras posiciones o incluso ramificaciones como grupos metilo. Esfingomielinas Esfingomileina. Negro: esfingosina. Rojo: fosfocolina. Se parecen, por supuesto, a las fosfatidilcolinas en estructura tridimensional y en propiedades generales ya que no tienen carga en sus cabezas polares. No poseen grupos fosfato.

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