China
Africa
Explore chapters and articles related to this topic
Nature, Function, and Biosynthesis of Surfactant Lipids
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
A fatty acid-binding protein has been isolated and characterized from rat lung tissue.301 This protein has high affinity for long-chain acyl-CoAs and stimulates acyl-CoA synthetase.300 Subsequently, it has been shown to enhance phosphatidic acid synthesis through stimulation of glycerophosphate acyltransferase activity; fatty acyl CoAs bound to the protein would represent preferential substrates for glycerophosphate acyltransferase. By contrast, this binding protein does not seem to activate lysophosphatidylcholine acyltransferase.302
The Changes in Hepatic Lipid and Carbohydrate Metabolism In Sepsis *
Published in Timothy R. Billiar, Ronald D. Curran, Hepatocyte and Kupffer Cell Interactions, 2017
We have begun to assess what factors may contribute to the fate of radiolabeled oleic acid, a monoenoic saturated fatty acid, and arachidonic acid, a polyunsaturated long-chain fatty acid, in cultured hepatocytes after incubation with either endotoxin-stimulated Kupffer cell supernatant or the cytokines IL-1, IL-6, and TNF. In our studies, the hepatocyte responds to the presence of Kupffer cell supernatant stimulated with LPS by significantly reducing the distribution of both labeled oleic acid into the triglyceride fraction found in the hepatocyte supernatant while increasing the extracellular levels of labeled free fatty acid (Figure 4). Similar changes were measured when the hepatocytes were incubated with labeled arachidonic acid. No changes were detected in the phospholipid fraction in the hepatocyte. These results agree with those of Rodrigez de Turco and Spitzer,77 who reported that the arachidonic acid-associated triglyceride fraction accounted for approximately 50 to 60% of the total labeled arachidonate esterified into glycerolipids and probably reflects a small, but metabolically very active acyl-storage site. Our results suggest a possible decreased efficiency of esterifying lipids by the acyl-CoA synthetase system that effects both the utilization of metabolic lipids (oleic acid) and structural fatty acids (arachidonate).
Lipid Metabolism in the Intestinal Tract and Its Modification by Ethanol
Published in Victor R. Preedy, Ronald R. Watson, Alcohol and the Gastrointestinal Tract, 2017
Prior to their utilization in the synthesis of TG, FAs must be activated to their CoA derivatives. The enzyme catalyzing this reaction is acyl-CoA synthetase. TGs are synthesized in the enterocyte by two distinct metabolic pathways; the MG pathway and the glycerophosphate pathway. In the MG pathway, absorbed 2-MGs are acylated by acyl-CoA in a stepwise manner with intermediate formation of diacylglycerol (diglyceride) to form TGs. The major enzymes involved in the MG pathway are monoglyceride acyl transferase and diglyceride acyl transferase. The MG pathway is primarily associated with the smooth ER (SER).25 In the glycerophosphate pathway, glycerophosphate is acylated by acyl-CoA to form phosphatidic acid. Then the phosphatidic acid is hydrolyzed to 1,2-DGs via the action of phosphatidate phosphohydrolase, and DGs are finally acylated to TGs. The glycerophosphate pathway is associated with the rough ER (RER).25
Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment
Published in Drug Delivery, 2023
Ling Zhang, Bing-Zhong Zhai, Yue-Jin Wu, Yin Wang
The function of acetate and acetate-metabolizing enzymes in cancer cells has recently been demonstrated (Schug et al., 2016). Both substrates could be oxidized when 13 C-glucose and 13 C-acetate were infused into mice with orthotopic glioblastomas. However, in plasma, the tumors oxidized more quickly than the nearby normal brain tissues did. Acetate oxidation has been seen in metastatic brain tumors, suggesting that this pathway is a common characteristic of tumors in the brain (Mashimo et al., 2014). Infusion of a similar mixture of 13 C-glucose and 13 C-acetate in human patients also revealed extensive acetate oxidation in gliomas and brain metastases. An Acyl-CoA Synthetase Short Chain 2 (ACSS2) deficient mouse model was used to examine the role of this enzyme in tumor growth (Huang et al., 2018). These embryonic fibroblasts lacking ACSS2 are unable to use exogenous acetate for lipogenesis and histone acetylation. Furthermore, ACSS2 knockout in two hepatocellular carcinoma models lessens the tumor burden (Huang et al., 2018; Bidkhori et al., 2018). According to the selective ACSS2 inhibitors hypothesis, targeting acetate metabolism may have a potent therapeutic effect in some types of cancer (Olson et al., 2016). Given the importance of the aforementioned cancer metabolic pathways, nanoparticles can be used to target specific metabolic sections in these pathways to identify potential cancer therapeutic strategies.
Targeting cellular energy metabolism- mediated ferroptosis by small molecule compounds for colorectal cancer therapy
Published in Journal of Drug Targeting, 2022
Gang Wang, Jun-Jie Wang, Xiao-Na Xu, Feng Shi, Xing-Li Fu
Fatty acid metabolic enzymes are related to the prognosis and progression of several cancers, including colorectal cancer [40,41]. Notably, acyl CoA synthetase (ACSL) expression and clinical outcomes indicate that ACSL1, which is used more for triglyceride synthesis [42], is upregulation in CRC [43]. Acylcarnitines are generated through the transfer of carnitine for CoA on acyl-CoA derivatives of long-chain FA by carnitine palmitoyltransferase (CPT), to transport them through the mitochondrial membrane [44]. Thus, elevated acylcarnitine levels can be due to increased CPT activity resulting from an increase in the cytoplasmic acyl-CoA substrate levels, such as the ACSL1 products. Regarding glycolytic perturbations, increased phosphoenolpyruvate (PEP) levels and normal pyruvate could be a reflection of less of a demand of TCA feeding from pyruvate (from carbohydrates) explaining a lower basal oxygen consumption rate (OCR), since a more energetic status is achieved through other alternative supplies, such as FAO, that could be fed by ACSL1 overexpression [45]. For instance, the FAO inhibitor etomoxir is insufficient for reversing the EMT phenotype of ACSL/SCD cells that, conversely, can be achieved upon a more drastic energetic restriction caused by the reactivation of AMP-activated protein kinase (AMPK) signalling upon metformin treatment [46].
An overview of the latest in state-of-the-art murine models for prostate cancer
Published in Expert Opinion on Drug Discovery, 2021
Elisabete Nascimento-Gonçalves, Fernanda Seixas, Rita Ferreira, Bruno Colaço, Belmiro Parada, Paula A. Oliveira
The various foundations and research centers in each country, as well as European centers and international funds, support a number of research projects in oncology – using clinical trials and animal experimentation. Currently in the PCa field, there are some ongoing projects. For example, AF Castillo and her team are working on the development of selective inhibitors for acyl-CoA synthetase 4, an isoenzyme involved in the development of tumor aggressiveness in PCa. A recently published paper that used PC-3 prostate-tumor xenografts treated with the novel inhibitor, PRGL493, in a study, reported a significant inhibition of tumor growth [189]. Leibold and colleagues developed a model to introduce genetic alterations relevant to the human disease directly into the prostate gland of GEMM mice, using tissue electroporation. Through this model, they showed a functional role for the WNT signaling pathway in driving PCa metastasis and validated these pathways as a therapeutic target in metastatic PCa [190]. A PDX-murine model was used to show that enzalutamide (androgen deprivation therapy) induced the expression of pro-oncogenic ephrin type-A receptor 2 (EphA2), a receptor overexpressed in several cancers and associated with poor prognosis [191]. In the same study, a PC-3 orthotopic xenograft model treated with agonistic EphA2 was effective in suppressing cell migration and tumor metastases. Hence, this investigation validates EphA2 as an potential target in metastatic PCa treatment [191].