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Some 40 years ago, there was a rumor in the research community that lipids are the stuff you have to throw away before starting biochemical experiments. This view has changed. Nowadays, it is widely accepted that lipids play an important role in many biochemical and cell biological processes. They are involved in the formation of biological membranes and therefore are important elements of organelle...
Phospholipids are the main components of biological membranes and as such act as the major permeability barrier between cells and the extracellular space, as well as defining the physical boundaries of intracellular organelles. Phospholipid types are defined by in large by their head groups that in turn are the major determinants of phospholipid function. Within a specific phospholipid type, heterogeneity...
Phospholipids represent the second family of lipids after the galactolipids in photosynthetic tissues and the first in non-photosynthetic tissues. Their distribution among the membranes of the secretory pathway and the various organelles shows extensive compartmentation. The metabolic pathways involved in phospholipid biosynthesis are also distributed between several organelles. As a consequence,...
In the yeast Saccharomyces cerevisiae, as in other eukaryotes, glycerophospholipids are important cellular components required for growth and cell proliferation. Besides their function as structural constituents of subcellular membranes, phospholipids contribute to the maintenance of organelle morphology, transport and sorting processes, and signal transduction. Synthesis of glycerophospholipids is...
Defects in eight different enzymes of cholesterol biosynthesis that result in serious clinical consequences have been identified. Most of these were identified in the last decade. One of these, the Smith-Lemli-Opitz syndrome is fairly common with an incidence of perhaps 1 in 20,000. Defects in 3β-hydroxysteroid Δ7-reductase are responsible for this syndrome. In severely affected SLO patients, cholesterol...
Higher plants synthesize a bewildering array of sterols, with sitosterol, stigmasterol, and 24-methylcholesterol as major compounds. All plant tissues contain free and conjugated sterols. The first steps of sterol biosynthesis occur via the classical acetate/mevalonate pathway, concomitantly with synthesis of many other isoprenoids. A crosstalk between cytosolic and plastid 2-C-methylerythritol phosphate...
Saccharomyces cerevisiae has been a major model system for the study of sterol biosynthesis and function. All of the genes encoding the enzymes involved in ergosterol biosynthesis have been isolated and characterized including those participating in the complex reactions involved in C-4 demethylation. Emerging information on sterol biosynthesis and its localization, storage of excess sterol,...
Mammalian isozymes of ACAT, DGAT, and MGAT are encoded by the ACAT and DGAT2 gene families. These enzymes catalyze the synthesis of neutral lipid cholesteryl esters (CE) and triacylglycerols (TG). CE and TG are the major constituents of the lipid core in the lipoprotein particles. In addition, CE is the major lipid material present in foam cells during development of atherosclerosis, while TG is the...
The biosynthesis of storage lipids (triacylglycerols) in higher plants is now known to occur via a number of different routes. These include the Kennedy pathway, using sequential acylation and acyl-CoA substrates. It has recently been observed that several other alternative pathways also operate, including acyl-CoA-independent enzymes, which appear to sequentially “enrich” storage lipids with polyunsaturated...
The reactions leading to the biosynthesis of neutral lipids are excellent targets for therapeutic intervention in several disease states including cardiovascular disease and obesity, where neutral lipid accumulation is a clear risk factor. Prior to developing such therapeutics, an understanding of the mechanism and physiological role of the numerous enzymes involved in neutral lipid synthesis is critical...
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite implicated in the regulation of vital biological processes. Ample evidence indicates that S1P acts as both an intracellular messenger and an extracellular ligand for a specific G protein-coupled receptor family. Cellular levels of S1P are tightly regulated in a spatio-temporal manner through its synthesis catalysed by sphingosine...
Plants contain a multiplicity of sphingolipid metabolites, such as long-chain bases, long-chain base phosphates, ceramides, glycosylceramides, phosphosphingolipids, and glycosyl inositol phosphorylceramide anchors of membrane proteins. Most of these compounds are also known from other eukaryotic organisms, but plant sphingolipids show some structural features that differ from those present in mammals...
Saccharomyces cerevisiae has been an invaluable tool for the dissection of sphingolipid metabolic pathways and cloning of enzymes involved in sphingolipid metabolism. Due to the biochemical conservation of these pathways in mammalian cells, information gained in yeast has greatly contributed to the understanding of sphingolipid formation and function in mammals. Sphingolipids are involved...
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