Detection of a homologous series of C26-C38 polyenoic fatty acids in the brain of patients without peroxisomes (Zellweger's syndrome).
Ontology highlight
ABSTRACT:
SUBMITTER: Poulos A
PROVIDER: S-EPMC1146726 | biostudies-other | 1986 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The polyenoic fatty acids with carbon chain lengths from 26 to 38 (very-long-chain fatty acids, VLCFA) previously detected in abnormal amounts in Zellweger syndrome brain have been shown to be n-6 derivatives and therefore probably derived by chain elongation of shorter-chain n-6 fatty acids such as linoleic acid and arachidonic acid. Polyenoic VLCFA are also present in Zellweger syndrome liver, but this tissue differs significantly from brain in that the saturated and mono-unsaturated derivatives are the major VLCFA. Zellweger syndrome brain polyenoic VLCFA are present in the neutral lipids predominantly in cholesterol esters, with smaller amounts in the non-esterified fatty acid and triacylglycerol fractions. These fatty acids are barely detectable in any of the major phospholipids, but are present in significant amounts in an unidentified minor phospholipid. The polyenoic VLCFA composition of this lipid differs markedly from that observed for all other lipids, as it contains high proportions of pentaenoic and hexaenoic fatty acids with 34, 36 and 38 carbon atoms. A polar lipid with the chromatographic properties in normal brain contains similar fatty acids. It is postulated that the polyenoic VLCFA may play an important role in normal brain and accumulate in Zellweger syndrome brain because of a deficiency in the peroxisomal beta-oxidation pathway, although a possible peroxisomal role in the control of carbon-chain elongation cannot be discounted.
| S-EPMC1148500 | biostudies-other
Project description:Rat brain has been shown to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38. These fatty acids are almost exclusively located in unusual molecular species of phosphatidylcholine at the sn-1 position of the glycerol backbone, whereas saturated, monoenoic and polyenoic fatty acids with less than 24 carbon atoms are present at the sn-2 position. Polyenoic VLCFA phosphatidylcholine in neonatal rat brain is enriched with n-6 pentaenoic and n-3 hexaenoic VLCFA with up to 36 carbon atoms, whereas the corresponding phospholipid in adult rat brain mainly contains n-6 tetraenoic and n-3 pentaenoic VLCFA with up to 38 carbon atoms. The total amount of polyenoic VLCFA associated with phosphatidylcholine is highest in the brain of immature animals. Polyenoic VLCFA phosphatidylcholine appears to be predominantly confined to nervous tissue in rats, and it is envisaged that this phospholipid is of physiological significance.
| S-EPMC1133699 | biostudies-other
Project description:In rat seminiferous tubules (ST), cells that contain polar and neutral lipids with long-chain polyenoic fatty acids (PUFA) and sphingomyelins (SM) and ceramides (Cer) with very long chain (VLC) PUFA of the n-6 series coexist. In this study, pachytene spermatocytes and round spermatids were isolated to determine how these lipids change during spermatogenesis. As the amount per cell of PUFA-rich glycerophospholipids (GPL) decreased with cell size, the 22:5/20:4 ratio increased with cell differentiation. The elovl2 and elovl5 genes, required for 22:5 formation, were expressed (mRNA) in both cell types. Residual bodies- particles with compacted organelles and materials discarded from late spermatids-concentrated cholesterol, 22:5-rich triacylglycerols, and GPL, including plasmalogens and phosphatidylserine. Species of SM and Cer with nonhydroxylated (n-) VLCPUFA (28:4, 30:5, and 32:5) predominated in pachytene spermatocytes, whereas species with the corresponding 2-hydroxy (2-OH) VLCPUFA prevailed in round spermatids. Thus, a dramatic increase in the 2-OH/n-VLCPUFA ratio in SM and Cer was a hallmark of differentiation. A substantial decrease of 2-OH SM occurred between spermatids and mature spermatozoa and 2-OH SM species were collected in residual bodies "en route" to Sertoli cells. Notably, spermatids and spermatozoa gained a significant amount of ceramides devoid of n-VLCPUFA but having 2-OH VLCPUFA as their main fatty acids.
| S-EPMC2936765 | biostudies-literature
Project description:In their transit from the caput to the cauda segments of the epididymis, rat spermatozoa undergo significant modifications in lipid content and composition. The amount of lipid phosphorus per cell decreases, and most lipid classes show specific changes in their constituent fatty acids. A depletion of phosphatidylcholine and phosphatidylethanolamine, concomitant with a virtually unchanged amount of the corresponding plasmalogens, are the major alterations, plasmenylcholine thereby becoming the major phospholipid. Diphosphatidylglycerol, sphingomyelin and the phosphoinositides decrease to a lesser extent or do not change at all, also resulting in relative increases with sperm maturation. Concerning the fatty acids, the proportions of oleate (C18:1, n-9) and linoleate (C18:2, n-6) in most lipids decrease on movement of sperm from caput to cauda, augmenting in turn the proportions of longer-chain (C20 to C24) and more unsaturated fatty acids. Docosapentaenoate (C22:5, n-6) is a major acyl chain present in all lipids at both stages, but uncommon long-chain polyenoic fatty acids of the n-9 series are also present, being almost exclusively found in the choline glycerophospholipids. These fatty acids are found to undergo the most significant changes during sperm maturation. They are minor components of plasmenylcholine in immature spermatozoa, but increase severalfold on maturation, representing more than half of the acyl chains of this major lipid in cells from the cauda. The high concentration of n-9 polyenes in mature sperm plasmenylcholine raises intriguing questions on the possible role epididymal cells may play in providing spermatozoa with such an unusual phospholipid. These plasmenylcholines could contribute to the characteristic lipid domain organization of the mature spermatozoa plasma membrane.
| S-EPMC1131019 | biostudies-other
Project description:The n-6 tetra- and pentaenoic fatty acids with carbon chain lengths greater than 32 found in normal brain are located predominantly in a separable species of phosphatidylcholine. A similar phospholipid is found in increased amounts in the brain of peroxisome-deficient (Zellweger's syndrome) patients, but the fatty acid composition differs in that penta- and hexaenoic derivatives predominate. Our data strongly suggest that the polyenoic very long chain fatty acids are confined to the sn-1 position of the glycerol moiety, while the sn-2 position is enriched in saturated, monounsaturated and polyunsaturated fatty acids with less than 24 carbon atoms. It is postulated that these unusual molecular species of phosphatidylcholine may play some, as yet undefined, role in brain physiology.
| S-EPMC1149355 | biostudies-other
Project description:Mast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the functions of many immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils through their selective production of multiple cytokines and chemokines. MCs generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors through both degranulation dependent and independent pathways. Recent studies suggested that metabolic shifts dictate the activation and granule content secretion by MCs, however the metabolic signaling promoting these events is at its infancy. Lipid metabolism is recognized as a pivotal immunometabolic regulator during immune cell activation. Peroxisomes are organelles found across all eukaryotes, with a pivotal role in lipid metabolism and the detoxification of reactive oxygen species. Peroxisomes are one of the emerging axes in immunometabolism. Here we identified the peroxisome as an essential player in MCs activation. We determined that lack of functional peroxisomes in murine MCs causes a significant reduction of interleukin-6, Tumor necrosis factor and InterleukinL-13 following immunoglobulin IgE-mediated and Toll like receptor 2 and 4 activation compared to the Wild type (WT) BMMCs. We linked these defects in cytokine release to defects in free fatty acids homeostasis. In conclusion, our study identified the importance of peroxisomal fatty acids homeostasis in regulating mast cell-mediated immune functions.
| S-EPMC9215104 | biostudies-literature
Project description:Peroxisomes are essential organelles for the specialized oxidation of a wide variety of fatty acids, but they are also able to degrade fatty acids that are typically handled by mitochondria. Using a combination of pharmacological inhibition and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 genome editing technology to simultaneously manipulate peroxisomal and mitochondrial fatty acid β-oxidation (FAO) in HEK-293 cells, we identified essential players in the metabolic crosstalk between these organelles. Depletion of carnitine palmitoyltransferase (CPT)2 activity through pharmacological inhibition or knockout (KO) uncovered a significant residual peroxisomal oxidation of lauric and palmitic acid, leading to the production of peroxisomal acylcarnitine intermediates. Generation and analysis of additional single- and double-KO cell lines revealed that the D-bifunctional protein (HSD17B4) and the peroxisomal ABC transporter ABCD3 are essential in peroxisomal oxidation of lauric and palmitic acid. Our results indicate that peroxisomes not only accept acyl-CoAs but can also oxidize acylcarnitines in a similar biochemical pathway. By using an Hsd17b4 KO mouse model, we demonstrated that peroxisomes contribute to the plasma acylcarnitine profile after acute inhibition of CPT2, proving in vivo relevance of this pathway. We summarize that peroxisomal FAO is important when mitochondrial FAO is defective or overloaded.-Violante, S., Achetib, N., van Roermund, C. W. T., Hagen, J., Dodatko, T., Vaz, F. M., Waterham, H. R., Chen, H., Baes, M., Yu, C., Argmann, C. A., Houten, S. M. Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4.
| S-EPMC6404569 | biostudies-literature
Project description:Background:Oleate-enriched triacylglycerides are well-suited for lubricant applications that require high oxidative stability. Fatty acid carbon chain length and degree of desaturation are key determinants of triacylglyceride properties and the ability to manipulate fatty acid composition in living organisms is critical to developing a source of bio-based oil tailored to meet specific application requirements. Results:We sought to engineer the oleaginous yeast Yarrowia lipolytica for production of high-oleate triacylglyceride oil. We studied the effect of deletions and overexpressions in the fatty acid and triacylglyceride synthesis pathways to identify modifications that increase oleate levels. Oleic acid accumulation in triacylglycerides was promoted by exchanging the native ?9 fatty acid desaturase and glycerol-3-phosphate acyltransferase with heterologous enzymes, as well as deletion of the ?12 fatty acid desaturase and expression of a fatty acid elongase. By combining these engineering steps, we eliminated polyunsaturated fatty acids and created a Y. lipolytica strain that accumulates triglycerides with >?90% oleate content. Conclusions:High-oleate content and lack of polyunsaturates distinguish this triacylglyceride oil from plant and algal derived oils. Its composition renders the oil suitable for applications that require high oxidative stability and further demonstrates the potential of Y. lipolytica as a producer of tailored lipid profiles.
| S-EPMC5941336 | biostudies-literature
Project description:When a single dose of X-rays is applied to the adult rat testis, stem spermatogonia are damaged, and spermatogenesis is interrupted. Supported by Sertoli cells, spermatogenic cells that endure irradiation complete their differentiation and gradually leave the testis as spermatozoa. In this study, the in vivo changes taking place a number of weeks after irradiation revealed cell-specific features of testicular lipid classes. A linear drop, taking about six weeks, in testis weight, nonlipid materials, free cholesterol, and 22:5n-6-rich glycerophospholipids took place with germ cell depletion. Sphingomyelins and ceramides with nonhydroxy very long-chain polyenoic fatty acids (n-VLCPUFA) disappeared in four weeks, together with the last spermatocytes, whereas species with 2-hydroxy VLCPUFA lasted for six weeks, disappearing with the last spermatids and spermatozoa. The amount per testis of 22:5n-6-rich triacylglycerols, unchanged for four weeks, fell between weeks 4 and 6, associating these lipids with spermatids and their residual bodies, detected as small, bright lipid droplets. In contrast, 22:5n-6-rich species of cholesterol esters and large lipid droplets increased in seminiferous tubules up to week 6, revealing they are Sertoli cell products. At week 30, the lipid and fatty acid profiles reflected the resulting permanent testicular involution. Our data highlight the importance of Sertoli cells in maintaining lipid homeostasis during normal spermatogenesis.
| S-EPMC2918443 | biostudies-literature
Project description:Fatty acids with carbon chain lengths greater than 22 (VLCFA) have been detected in boar, ram, bull and human spermatozoa. Saturated and mono-unsaturated fatty acids were present in all spermatozoa but, except for human spermatozoa, polyenoic fatty acids were quantitatively the most important components. Marked differences in polyenoic fatty acid composition were observed. Whereas human spermatozoa contain predominantly di-, tri- and tetraenoic fatty acids with up to 32 carbon atoms, boar, ram and bull spermatozoa also contain pentaenoic and/or hexaenoic acids with up to 34 carbon atoms. Human and boar spermatozoa differ markedly from those of the ram and bull in that only n-6 series acids are present.
| S-EPMC1147503 | biostudies-other