9 Mechanisms and mediators of neutral lipid biosynthesis in eukaryotic cells

Oelkers, Peter; Sturley, Stephen L.

doi:10.1007/978-3-540-40999-1_10

Cited by 8 publications

(23 citation statements)

References 87 publications

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“…ACAT1 is widely expressed with the highest levels in macrophages, steroidogenic tissues, sebaceous glands, and atherosclerotic lesions. ACAT2, on the other hand, is limited in its expression to the liver and small intestine (9,79). The tissue distribution of the ACAT enzymes suggests that ACAT1 is involved primarily with deposition of CE into cytoplasmic lipid droplets, whereas ACAT2 is likely involved with lipoprotein assembly.…”

Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

“…DAG is esterified to form TAG by the DGAT reaction (79). There are at least two independent mammalian enzymes known to catalyze this reaction, DGAT1 and DGAT2 (34).…”

Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

“…This homology is maintained in the whole human DGAT2 gene family and includes the conservation of residues at the active sites of bacterial glycerol-3-phosphate acyltransferases. Both the ACAT and DGAT2 enzyme families are conserved across multiple organisms, including yeast and plants (79), as is the PDAT family.…”

Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

“…Cells that lack ARE1 and ARE2 are unable to esterify sterols yet are viable due to adaptive downregulation of ergosterol synthesis. Whereas ARE2 prefers ergosterol as its substrate, ARE1 esterifies a wider range of sterols and may serve as both a detoxification and storage reaction for sterol biosynthetic intermediates (79).…”

Section: Model Systems For Studying Acyltransferasesmentioning

confidence: 99%

“…Furthermore, deletion of ARE1 in such a strain obliterates the ability of such cells to synthesize SE and TAG. Subsequently, utilization of such strains devoid of neutral lipids has facilitated the study of mammalian enzymes involved in neutral lipid synthesis (79).…”

Section: Model Systems For Studying Acyltransferasesmentioning

confidence: 99%

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The genetics of neutral lipid biosynthesis: an evolutionary perspective

Turkish¹,

Sturley²

2009

American Journal of Physiology-Endocrinology and Metabolism

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Turkish AR, Sturley SL. The genetics of neutral lipid biosynthesis: an evolutionary perspective. Am J Physiol Endocrinol Metab 297: E19 -E27, 2009. First published December 30, 2008 doi:10.1152/ajpendo.90898.2008.-The storage of fatty acids and fatty alcohols in the form of neutral lipids such as triacylglycerol (TAG), cholesteryl ester (CE), and wax ester (WE) serves to provide reservoirs for membrane formation and maintenance, lipoprotein trafficking, lipid detoxification, evaporation barriers, and fuel in times of stress or nutrient deprivation. This ancient process likely originated in actinomycetes and has persisted in eukaryotes, albeit by different molecular mechanisms. A surfeit of neutral lipids is strongly, perhaps causally, related to several human diseases such as diabetes mellitus, obesity, atherosclerosis and nonalcoholic fatty liver disease. Therefore, understanding the metabolic pathways of neutral lipid synthesis and the roles of the enzymes involved may facilitate the development of new therapeutic interventions for these syndromes. STORAGE OF FATTY ACIDS, fatty alcohols, and sterols in the form of neutral lipids serves to allocate resources for potential use in vital functions such as membrane formation, epidermal integrity, bile acid synthesis, lipoprotein trafficking, and steroidogenesis. Neutral lipids, such as cholesteryl ester (CE), triacylglycerol (TAG), and wax ester (WE), provide organisms with inert forms of energy used in conditions of nutrient deprivation and environmental stress. They also provide an excellent "sink" to buffer the toxic effects of fatty acids and fatty alcohols. In times of plenty (such as a typical Western diet), energy in the form of fat is efficiently stored, but with consequences. Elevated cytoplasmic deposition of neutral lipids (primarily CE and TAG) is a significant risk factor for several disease pathologies, including diabetes, obesity, atherosclerosis, and nonalcoholic fatty liver disease (41,53,101). For example, the accumulation of CE in smooth muscle cells and macrophages in the vessel wall comprises the earliest recognizable stage in atherosclerotic plaque formation (90). Furthermore, serum levels of TAG and total cholesterol are independent risk factors for atherosclerosis. Similarly, the loading of TAG into the cytoplasm of adipocytes represents the basic unit of obesity and thus accounts for fat accumulation in all obese syndromes.TAG, a fatty acyl ester derivative of glycerol, represents the major energy depot of all eukaryotic and some bacterial cells (16) and is formed primarily via an acyl-CoA diacylglycerol acyltransferase (DGAT) reaction, although in some organisms acyl-CoA-independent reactions also contribute to these pools. The energy of complete oxidation of the alkyl chains of TAG (38 KJ/g) is more than twice the same weight of carbohydrate or protein, and unlike polysaccharide, TAG carries no extra weight as water of solvation. Furthermore, TAG is deposited into cytoplasmic lipid droplets and thus has no effect on the osmolarity of the...

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Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

“…DAG is esterified to form TAG by the DGAT reaction (79). There are at least two independent mammalian enzymes known to catalyze this reaction, DGAT1 and DGAT2 (34).…”

Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

Section: Eukaryotic Acyltransferasesmentioning

confidence: 99%

Section: Model Systems For Studying Acyltransferasesmentioning

confidence: 99%

Section: Model Systems For Studying Acyltransferasesmentioning

confidence: 99%

See 3 more Smart Citations

The genetics of neutral lipid biosynthesis: an evolutionary perspective

Turkish¹,

Sturley²

2009

American Journal of Physiology-Endocrinology and Metabolism

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Co‐utilization of amino acid‐rich wastes and glycerol for microbial lipid production

Kamal

Huang

Wang

et al. 2021

Biofuels Bioprod Bioref

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Microbial lipids are considered to be potential raw materials for biodiesel production. However, the costs of such a process remain high due to the use of expensive feedstocks for microbial lipid production. The meat industry and biodiesel refineries generate amino acid (AA) wastes and crude glycerol, respectively, which could be explored as relatively cheap feedstocks for oleaginous yeasts. Unfortunately, AA wastes have a high nitrogen content and crude glycerol contains several impurities, discouraging microbial lipid production. Here, glycerol was co-used with AA, or with AA blends with compositional profiles matching those of different meats, so that the media had favorable carbon-tonitrogen (C/N) ratios to promote AA conversion into lipids using the oleaginous yeast Cryptococcus curvatus ATCC 20509 under two-stage culture conditions. Co-utilization of glycerol and AA resulted in improved lipid production. The highest lipid yield of 20.9 g 100 g -1 was achieved with lysine and glycerol, where the lipid yield was 13.9 g 100 g -1 , using an AA blend of similar composition to sheep viscera and glycerol. The lipid products comprised over 93% of 16 and 18 carbon-containing fatty acids, showing high potential for biodiesel production. The co-use of glycerol with AA improved AA conversion into lipids while decreasing the inhibitory effects at relatively high AA concentrations. The utilization of crude glycerol and AA-rich wastes from the meat industry could help both the development of biorefineries and waste minimization.

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The life cycle of neutral lipids: synthesis, storage and degradation

Athenstaedt

Daum

2006

Cell. Mol. Life Sci.

276

191

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Triacylglycerols (TAGs), steryl esters (SEs) and wax esters (WEs) form the group of neutral lipids. Whereas TAGs are present in all types of cell, the occurrence of SEs in prokaryotes is questionable, and the presence of WEs as storage molecules is restricted to plants and a few bacteria. Here, we summarize recent knowledge on the formation, storage and degradation of TAGs and SEs in various cell types. We describe the biochemical pathways involved in TAG and SE synthesis and discuss the subcellular compartmentation of these processes. Recently, several novel enzymes governing the metabolism of storage lipids have been identified and characterized. Regulatory aspects of neutral lipid storage are just beginning to be understood. Finally, we describe consequences of defects in neutral lipid metabolism. Since severe diseases like atherosclerosis, obesity and type 2 diabetes are caused by lipid accumulation, mechanisms underlying neutral lipid synthesis, depot formation and mobilization are of major interest for curing such diseases that are increasingly associated with modern civilization.

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9 Mechanisms and mediators of neutral lipid biosynthesis in eukaryotic cells

Cited by 8 publications

References 87 publications

The genetics of neutral lipid biosynthesis: an evolutionary perspective

The genetics of neutral lipid biosynthesis: an evolutionary perspective

Co‐utilization of amino acid‐rich wastes and glycerol for microbial lipid production

The life cycle of neutral lipids: synthesis, storage and degradation

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