Acyl-CoA

About: Acyl-CoA is a research topic. Over the lifetime, 527 publications have been published within this topic receiving 25134 citations. The topic is also known as: Acyl Coenzyme A.

Concerted regulation of free arachidonic acid and hormone-induced steroid synthesis by acyl-CoA thioesterases and acyl-CoA synthetases in adrenal cells

Abstract: Although the role of arachidonic acid (AA) in the regulation of steroidogenesis is well documented, the mechanism for AA release is not clear. Therefore, the aim of this study was to characterize the role of an acyl-CoA thioesterase (ARTISt) and an acyl-CoA synthetase as members of an alternative pathway in the regulation of the intracellular levels of AA in steroidogenesis. Purified recombinant ARTISt releases AA from arachidonoyl-CoA (AA-CoA) with a Km of 2 µm. Antibodies raised against recombinant acyl-CoA thioesterase recognize the endogenous protein in both adrenal tissue and Y1 adrenal tumor cells by immunohistochemistry and immunocytochemistry and Western blot. Stimulation of Y1 cells with ACTH significantly stimulated endogenous mitochondrial thioesterases activity (1.8-fold). Nordihydroguaiaretic acid (NDGA), an inhibitor of AA release known to affect steroidogenesis, affects the in vitro activity of recombinant ARTISt and also the endogenous mitochondrial acyl-CoA thioesterases. ACTH-stimulated steroid synthesis in Y1 cells was significantly inhibited by a synergistic effect of NDGA and triacsin C an inhibitor of the AA-CoA synthetase. The apparent IC50 for NDGA was reduced from 50 µm to 25, 7.5 and 4.5 µm in the presence of 0.1, 0.5 and 2 µm triacsin C, respectively. Our results strongly support the existence of a new pathway of AA release that operates in the regulation of steroid synthesis in adrenal cells.

The biochemistry of copper deficiency. II. Synthetic processes.

Abstract: The biochemistry of copper deficiency is studied in order to gain some understanding of the metabolic disturbances which lead to demyelination of the central nervous system in disease. In the preceding paper we reported our investigation of the enzyme systems, blood chemistry and amino-acid excretion in copper-deficient rats, and in this paper extend the study to investigate the syntheses of phospholipid, long-chain fatty acids, ribose nucleic acid, protein and protohaem. Phospholipid synthesis is found to be depressed considerably in copper deficiency. This is due to a failure in the process of condensation of acyl CoA with α-glycerophosphate to form phosphatidic acids. The reasons are discussed. The syntheses of long-chain fatty acids and ribose nucleic acid are normal, whilst the synthesis of protein is inconstantly affected by copper deficiency. Protohaem synthesis is depressed by a degree which exactly parallels the anaemia. The conclusion is drawn that the anaemia is due to a decrease in haematopoiesis rather than an increased destruction of red cells. The possible interrelationships of the disturbances of phospholipid synthesis and cytochrome oxidase activity and the relevance of each to demyelination of the central nervous system are discussed.

FadR-Based Biosensor-Assisted Screening for Genes Enhancing Fatty Acyl-CoA Pools in Saccharomyces cerevisiae.

Abstract: Fatty acid-derived compounds have a range of industrial applications, from chemical building blocks to biofuels. Due to the highly dynamic nature of fatty acid metabolism, it is difficult to identify genes modulating fatty acyl-CoA levels using a rational approach. Metabolite biosensors can be used to screen genes from large-scale libraries in vivo in a high throughput manner. Here, a fatty acyl-CoA sensor based on the transcription factor FadR from Escherichia coli was established in Saccharomyces cerevisiae and combined with a gene overexpression library to screen for genes increasing the fatty acyl-CoA pool. Fluorescence-activated cell sorting, followed by data analysis, identified genes enhancing acyl-CoA levels. From these, overexpression of RTC3, GGA2, and LPP1 resulted in about 80% increased fatty alcohol levels. Changes in fatty acid saturation and chain length distribution could also be observed. These results indicate that the use of this acyl-CoA biosensor combined with a gene overexpression library allows for identification of gene targets improving production of fatty acids and derived products.