Functional flexibility as a prelude to signal diversity? Role of a fatty acyl reductase in moth pheromone evolution

Sphingolipids are bioactive lipids responsible for regulating diverse cellular functions such as proliferation, migration, senescence, and death. These lipids are characterized by a long-chain sphingosine backbone amide-linked to a fatty acyl chain with variable length. The length of the fatty acyl chain is determined by specific ceramide synthases, and this fatty acyl length also determines the sphingolipid’s specialized functions within the cell. One function in particular, the regulation of the selective autophagy of mitochondria, or mitophagy, is closely regulated by ceramide, a key regulatory sphingolipid. Mitophagy alterations have important implications for cancer cell proliferation, response to chemotherapeutics, and mitophagy-mediated cell death. This review will focus on the alterations of ceramide synthases in cancer and sphingolipid regulation of lethal mitophagy, concerning cancer therapy.

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L-Carnitine in Drosophila: A Review

Antioxidants ◽

10.3390/antiox9121310 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1310

Author(s):

Maria Rosaria Carillo ◽

Carla Bertapelle ◽

Filippo Scialò ◽

Mario Siervo ◽

Gianrico Spagnuolo ◽

...

Keyword(s):

Transport System ◽

Essential Role ◽

Energy Homeostasis ◽

Current Knowledge ◽

Fatty Acyl ◽

Amino Acid Derivative ◽

Carnitine Transport ◽

Human Transport ◽

Drosophila Models

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.

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How do mechanosensitive channels sense membrane tension?

Biochemical Society Transactions ◽

10.1042/bst20160018 ◽

2016 ◽

Vol 44 (4) ◽

pp. 1019-1025 ◽

Cited By ~ 14

Author(s):

Tim Rasmussen

Keyword(s):

Membrane Lipids ◽

Osmotic Shock ◽

Md Simulations ◽

Fatty Acyl ◽

Membrane Bilayer ◽

Cross Sectional ◽

Conducting Path ◽

Lipid Chain ◽

Acyl Chains

Mechanosensitive (MS) channels provide protection against hypo-osmotic shock in bacteria whereas eukaryotic MS channels fulfil a multitude of important functions beside osmoregulation. Interactions with the membrane lipids are responsible for the sensing of mechanical force for most known MS channels. It emerged recently that not only prokaryotic, but also eukaryotic, MS channels are able to directly sense the tension in the membrane bilayer without any additional cofactor. If the membrane is solely viewed as a continuous medium with specific anisotropic physical properties, the sensitivity towards tension changes can be explained as result of the hydrophobic coupling between membrane and transmembrane (TM) regions of the channel. The increased cross-sectional area of the MS channel in the active conformation and elastic deformations of the membrane close to the channel have been described as important factors. However, recent studies suggest that molecular interactions of lipids with the channels could play an important role in mechanosensation. Pockets in between TM helices were identified in the MS channel of small conductance (MscS) and YnaI that are filled with lipids. Less lipids are present in the open state of MscS than the closed according to MD simulations. Thus it was suggested that exclusion of lipid fatty acyl chains from these pockets, as a consequence of increased tension, would trigger gating. Similarly, in the eukaryotic MS channel TRAAK it was found that a lipid chain blocks the conducting path in the closed state. The role of these specific lipid interactions in mechanosensation are highlighted in this review.

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Expansion of the fatty acyl reductase gene family shaped pheromone communication in Hymenoptera

10.1101/362509 ◽

2018 ◽

Author(s):

Michal Tupec ◽

Aleš Buček ◽

Heiko Vogel ◽

Václav Janoušek ◽

Darina Prchalová ◽

...

Keyword(s):

Fatty Acid ◽

Gene Family ◽

Fat Body ◽

Functional Characterization ◽

Acid Methyl Ester ◽

Fatty Acyl ◽

Sequencing Analysis ◽

Pheromone Communication ◽

Marking Pheromone ◽

Fatty Acyl Reductase

AbstractThe conserved fatty acyl reductase (FAR) family is involved in biosynthesis of fatty alcohols that serve a range of biological roles. In moths, butterflies (Lepidoptera), and bees (Hymenoptera), FARs biosynthesize fatty alcohol pheromones participating in mate-finding strategies. Using a combination of next-generation sequencing, analysis of transposable elements (TE) in the genomic environment of FAR genes, and functional characterization of FARs from Bombus lucorum, B. lapidarius, and B. terrestris, we uncovered a massive expansion of the FAR gene family in Hymenoptera, presumably facilitated by TEs. Expansion occurred in the common ancestor of bumblebees (Bombini) and stingless bees (Meliponini) after their divergence from the honeybee lineage. We found that FARs from the expanded FAR-A orthology group contributed to the species-specific male marking pheromone composition. Our results indicate that TE-mediated expansion and functional diversification of the FAR gene family played a key role in the evolution of pheromone communication in the crown group of Hymenoptera.AbbreviationsMMP: male marking pheromone, FA: fatty acid, FAME: fatty acid methyl ester, FAR: fatty acyl reductase, LG: labial gland, FB: fat body, TE: transposable element.

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Fatty Alcohols for Wax Esters in Marinobacter aquaeolei VT8: Two Optional Routes in the Wax Biosynthesis Pathway

Applied and Environmental Microbiology ◽

10.1128/aem.02420-13 ◽

2013 ◽

Vol 79 (22) ◽

pp. 7055-7062 ◽

Cited By ~ 26

Author(s):

Eric M. Lenneman ◽

Janet M. Ohlert ◽

Nagendra P. Palani ◽

Brett M. Barney

Keyword(s):

Fatty Alcohol ◽

Fatty Acyl ◽

Wax Esters ◽

Transcriptional Analysis ◽

Wax Ester ◽

Fatty Aldehyde ◽

Marinobacter Aquaeolei

ABSTRACTThe biosynthesis of wax esters in bacteria is accomplished by a unique pathway that combines a fatty alcohol and a fatty acyl coenzyme A substrate. Previousin vitroenzymatic studies indicated that two different enzymes could be involved in the synthesis of the required fatty alcohol inMarinobacter aquaeoleiVT8. In this study, we demonstrate through a series of gene deletions and transcriptional analysis that either enzyme is capable of fulfilling the role of providing the fatty alcohol required for wax ester biosynthesisin vivo, but evolution has clearly selected one of these, a previously characterized fatty aldehyde reductase, as the preferred enzyme to perform this reaction under typical wax ester-accumulating conditions. These results complement previousin vitrostudies and provide the first glimpse into the role of each enzymein vivoin the native organism.

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"Dehydrogenase" and "Oxidase" Reactions of Medium-Chain Fatty Acyl-CoA Dehydrogenase Utilizing Chromogenic Substrates: Role of the 3',5'-Adenosine Diphosphate Moiety of the Coenzyme A Thioester in Catalysis

Biochemistry ◽

10.1021/bi00014a016 ◽

1995 ◽

Vol 34 (14) ◽

pp. 4625-4632 ◽

Cited By ~ 8

Author(s):

D. K. Srivastava ◽

N. Ravi Kumar ◽

Kevin L. Peterson

Keyword(s):

Coenzyme A ◽

Adenosine Diphosphate ◽

Fatty Acyl ◽

Chromogenic Substrates ◽

Medium Chain

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Towards Employee Creativity in the Healthcare Sector: Investigating the Role of Polychronicity, Job Engagement and Functional Flexibility

Healthcare ◽

10.3390/healthcare9070837 ◽

2021 ◽

Vol 9 (7) ◽

pp. 837

Author(s):

Junaid Waheed ◽

Wen Jun ◽

Zahid Yousaf ◽

Magdalena Radulescu ◽

Hadi Hussain

Keyword(s):

Healthcare Sector ◽

Job Engagement ◽

Employee Creativity ◽

Cross Sectional ◽

Job Commitment ◽

Individual Level ◽

Functional Flexibility ◽

Mediating Role ◽

Regression Techniques

Given the importance of individual level creativity, this paper investigates the influence of employee polychronicity on employee creativity among nurses in the healthcare sector. The current research also tests how job engagement acts as a mediator between employees’ polychronicity and creativity. Finally, thepaper analyzes the role of functional flexibility as a moderator that enhances the influence of polychronicity on employee creativity. The current paper presents empirical research, and cross-sectional data were gathered from 457 nurses (Subordinate Staff) and 127 doctors (Supervisors) working in 37DHQ (District Head Quarters) hospitals in Pakistan. Descriptive statistics, correlation, and multiple-regression techniques were applied for analyzing the collected data. The findings proved that the nurses’ polychronic attitude increases their creativity. Findings revealed that job commitment plays a mediating role between polychronicity and employee creativity. The findings proved that functional flexibility enhances the link between polychronicity and creativity. This research has contributed to both theory and managerial practice about the interplay of polychronicity, creativity, job engagement, and functional flexibility among nurses. The management in practice should focus on employee attitude, i.e., polychronicity, for improving their creativeness.

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A Study on the Effect of Lysolecithin and Phospholipase A on Membrane-Bound Galactosyltransferase

Canadian Journal of Biochemistry ◽

10.1139/o74-147 ◽

1974 ◽

Vol 52 (11) ◽

pp. 1053-1066 ◽

Cited By ~ 33

Author(s):

Sailen Mookerjea ◽

James W. M. Yung

Keyword(s):

Liver Microsomes ◽

Fatty Acyl ◽

Phospholipase A ◽

Synthetase Activity ◽

Rat Liver Microsomes ◽

Physiological Concentration ◽

Activation Effect ◽

Membrane Bound ◽

Hydrolysis Of

Addition of lysolecithin caused very marked activation of UDP-galactose:glycoprotein galactosyltransferase in rat liver microsomes and in Golgi-rich membranes. Lysolecithin activated galactosyltransferase when the enzyme was assayed both with endogenous acceptor and with exogenous proteins or monosaccharides as acceptors. Lactose synthetase activity in presence of α-lactalbumin was also stimulated by lysolecithin. Lecithin, lysophosphatidylethanolamine, lysophosphatidic acid, and glycerophosphorylcholine did not activate the enzyme, suggesting that both fatty acyl and phosphorylcholine groups of the lysolecithin molecule are required for the observed activation. The degree of activation was about the same when myristoyl-, palmitoyl-, oleoyl-, or stearoyllysolecithin were tested. The activation by lysolecithin was observed well within the physiological concentration of the lipid in the liver cell. Saturating amounts of Triton masked the effect of lysolecithin.Brief preincubation with phospholipase A activated the enzyme and generated lysolecithin in the membranes. Triton and lysolecithin activated the enzyme without any lag time, whereas phospholipase A activation was dependent on preincubation and also on an alkaline pH favorable for the hydrolysis of phospholipid. EDTA blocked the activation effect of phospholipase A but had no effect on activation by lysolecithin. Albumin and cholesterol opposed the effects of lysolecithin and phospholipase A on the enzyme. Two successive incubations of the microsomes with lysolecithin caused considerable release of the enzyme into the soluble fraction. The role of lysolecithin in the activation of the enzyme is probably related to the solubilization of the membrane and consequent enhanced interaction of the enzyme with substrate. Lysolecithin also activated N-acetylglucosaminyl- and sialyltransferase activities in microsomes. A possible role of lysolecithin is indicated in the regulation of glycosylation reactions in mammalian system.

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Biochemical and physiological function of stearoyl-CoA desaturase

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90897.2008 ◽

2009 ◽

Vol 297 (1) ◽

pp. E28-E37 ◽

Cited By ~ 335

Author(s):

Chad M. Paton ◽

James M. Ntambi

Keyword(s):

Metabolic Diseases ◽

De Novo ◽

Metabolic Response ◽

Control Point ◽

Lipid Synthesis ◽

Monounsaturated Fatty Acids ◽

Fatty Acyl ◽

Physiological Importance ◽

Stearoyl Coa Desaturase

A key and highly regulated enzyme that is required for the biosynthesis of monounsaturated fatty acids is stearoyl-CoA desaturase (SCD), which catalyzes the D9- cis desaturation of a range of fatty acyl-CoA substrates. The preferred substrates are palmitoyl- and stearoyl-CoA, which are converted into palmitoleoyl- and oleoyl-CoA respectively. Oleate is the most abundant monounsaturated fatty acid in dietary fat and is therefore readily available. Studies of mice that have a naturally occurring mutation in the SCD-1 gene isoform as well as a mouse model with a targeted disruption of the SCD gene (SCD-1−/−) have revealed the role of de novo synthesized oleate and thus the physiological importance of SCD-1 expression. SCD-1 deficiency results in reduced body adiposity, increased insulin sensitivity, and resistance to diet-induced obesity. The expression of several genes of lipid oxidation are upregulated, whereas lipid synthesis genes are downregulated. SCD-1 was also found to be a component of the novel metabolic response to the hormone leptin. Therefore, SCD-1 appears to be an important metabolic control point, and inhibition of its expression could be of benefit for the treatment of obesity, diabetes, and other metabolic diseases. In this article, we summarize the recent and timely advances concerning the important role of SCD in the biochemistry and physiology of lipid metabolism.

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