A study of the fatty acid metabolism of the yeast Pityrosporum ovale.
Ontology highlight
ABSTRACT:
SUBMITTER: Wilde PF
PROVIDER: S-EPMC1198797 | biostudies-other | 1968 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:S-Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S-adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition.
| S-EPMC5900771 | biostudies-literature
Project description:Genome-scale metabolic models are built using information from an organism's annotated genome and, correspondingly, information on reactions catalyzed by the set of metabolic enzymes encoded by the genome. These models have been successfully applied to guide metabolic engineering to increase production of metabolites of industrial interest. Congruity between simulated and experimental metabolic behavior is influenced by the accuracy of the representation of the metabolic network in the model. In the interest of applying the consensus model of Saccharomyces cerevisiae metabolism for increased productivity of triglycerides, we manually evaluated the representation of fatty acid, glycerophospholipid, and glycerolipid metabolism in the consensus model (Yeast v6.0). These areas of metabolism were chosen due to their tightly interconnected nature to triglyceride synthesis. Manual curation was facilitated by custom MATLAB functions that return information contained in the model for reactions associated with genes and metabolites within the stated areas of metabolism. Through manual curation, we have identified inconsistencies between information contained in the model and literature knowledge. These inconsistencies include incorrect gene-reaction associations, improper definition of substrates/products in reactions, inappropriate assignments of reaction directionality, nonfunctional ?-oxidation pathways, and missing reactions relevant to the synthesis and degradation of triglycerides. Suggestions to amend these inconsistencies in the Yeast v6.0 model can be implemented through a MATLAB script provided in theSupplementary Materials, Supplementary Data S1(Supplementary Data are available online at www.liebertpub.com/ind).
| S-EPMC3963290 | biostudies-literature
Project description:Cancer cells often have characteristic changes in metabolism. Cellular proliferation, a common feature of all cancers, requires fatty acids for synthesis of membranes and signaling molecules. Here, we provide a view of cancer cell metabolism from a lipid perspective, and we summarize evidence that limiting fatty acid availability can control cancer cell proliferation.
| S-EPMC3742569 | biostudies-literature
Project description:The emergence of bone as an endocrine organ able to influence whole body metabolism, together with comorbid epidemics of obesity, diabetes, and osteoporosis, have prompted a renewed interest in the intermediary metabolism of the osteoblast. To date, most studies have focused on the utilization of glucose by this specialized cell, but the oxidation of fatty acids results in a larger energy yield. Osteoblasts express the requisite receptors and catabolic enzymes to take up and then metabolize fatty acids, which appears to be required during later stages of differentiation when the osteoblast is dedicated to matrix production and mineralization. In this article, we provide an overview of fatty acid ?-oxidation and highlight studies demonstrating that the skeleton plays a significant role in the clearance of circulating lipoproteins and non-esterified fatty acids. Additionally, we review the requirement for long-chain fatty acid metabolism during post-natal bone development and the effects of anabolic stimuli on fatty acid utilization by osteoblasts. These recent findings may help to explain the skeletal manifestations of human diseases associated with impaired lipid metabolism while also providing additional insights into the metabolic requirements of skeletal homeostasis.
| S-EPMC5832496 | biostudies-literature
Project description:As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.
| S-EPMC8230306 | biostudies-literature
Project description:While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analysing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type ?-oxidation of fatty acids [acyl-coenzyme A (CoA) dehydrogenase, enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase] with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three ?-oxidation enzymes working in the reverse direction could potentially catalyse biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications.
| S-EPMC4019937 | biostudies-literature
Project description:A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 ?M affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 ? and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.
| S-EPMC3360150 | biostudies-literature
Project description:A common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K-AKT-mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.
| S-EPMC6964678 | biostudies-literature
Project description:Fatty acid metabolism, including the de novo synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.
| S-EPMC8795701 | biostudies-literature
Project description:Polyunsaturated fatty acids (PUFA) play important roles in the normal physiology and in pathological states including inflammation and cancer. While much is known about the biosynthesis and biological activities of eicosanoids derived from ω6 PUFA, our understanding of the corresponding ω3 series lipid mediators is still rudimentary. The purpose of this review is not to offer a comprehensive summary of the literature on fatty acids in prostate cancer but rather to highlight some of the areas where key questions remain to be addressed. These include substrate preference and polymorphic variants of enzymes involved in the metabolism of PUFA, the relationship between de novo lipid synthesis and dietary lipid metabolism pathways, the contribution of cyclooxygenases and lipoxygenases as well as terminal synthases and prostanoid receptors in prostate cancer, and the potential role of PUFA in angiogenesis and cell surface receptor signaling.
| S-EPMC3865857 | biostudies-literature