scholarly journals MMPL-Family Proteins in Bacteria, Protozoa, Fungi, Plants and Animals: A Bioinformatics and Structural Investigation

2021 ◽  
Author(s):  
Eric Oldfield ◽  
Satish R. Malwal
Keyword(s):  
Fatty Acid ◽  
Cell Function ◽  
Proton Translocation ◽  
Domain Architecture ◽  
Life Forms ◽  
Active Site Residues ◽  
Fatty Acid Transporter ◽  
Lipid Transporters ◽  
Tm Domain ◽  
Trehalose Monomycolate

Lipid transporters play an important role in most if not all organisms, ranging from bacteria to humans. For example, in Mycobacterium tuberculosis, the trehalose monomycolate transporter MmpL3 is involved in cell wall biosynthesis, while in humans, cholesterol transporters are involved in normal cell function as well as in disease. Here, using structural and bioinformatics information, we propose that there are proteins that also contain “MmpL3-like” (MMPL) transmembrane (TM) domains in many protozoa, including Trypanosoma cruzi, as well as in the bacterium Staphylococcus aureus, where the fatty acid transporter FarE has the same set of “active-site” residues as those found in the mycobacterial MmpL3s, and in T. cruzi. We also show that there are strong sequence and predicted structural similarities between the TM proton-translocation domain seen in the X-ray structures of mycobacterial MmpL3s and several human as well as fungal lipid transporters, leading to the proposal that there are similar proteins in apicomplexan parasites, and in plants. The animal, fungal, apicomplexan and plant proteins have larger extra-membrane domains than are found in the bacterial MmpL3, but they have a similar TM domain architecture, with the introduction of a (catalytically essential) Phe>His residue change, and a Ser/Thr H-bond network, involved in H -transport. Overall, the results are of interest since they show that MMPL-family proteins are present in essentially all life-forms: archaea, bacteria, protozoa, fungi, plants and animals and, where known, they are involved in “lipid” (glycolipid, phospholipid, sphingolipid, fatty acid, cholesterol, ergosterol) transport, powered by transmembrane molecular pumps having similar structures.

scholarly journals Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing

2009 ◽  
Vol 297 (3) ◽  
pp. R655-R664 ◽  
Author(s):  
Christelle Le Foll ◽  
Boman G. Irani ◽  
Christophe Magnan ◽  
Ambrose A. Dunn-Meynell ◽  
Barry E. Levin
Keyword(s):  
Fatty Acid ◽  
Energy Homeostasis ◽  
Cell Function ◽  
Uncoupling Protein ◽  
Pharmacological Agents ◽  
Species Formation ◽  
Metabolic States ◽  
Fatty Acid Transporter ◽  
Metabolic Sensing ◽  
Long Chain

We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity as a potential means of regulating energy homeostasis. Fura-2 calcium (Ca2+) and membrane potential dye imaging, together with pharmacological agents, were used to assess the mechanisms by which oleic acid (OA) alters the activity of dissociated VMN neurons from 3- to 4-wk-old rats. OA excited up to 43% and inhibited up to 29% of all VMN neurons independently of glucose concentrations. In those neurons excited by both 2.5 mM glucose and OA, OA had a concentration-dependent effective excitatory concentration (EC50) of 13.1 nM. Neurons inhibited by both 2.5 mM glucose and OA had an effective inhibitory concentration (IC50) of 93 nM. At 0.5 mM glucose, OA had markedly different effects on these same neurons. Inhibition of carnitine palmitoyltransferase, reactive oxygen species formation, long-chain acetyl-CoA synthetase and ATP-sensitive K+ channel activity or activation of uncoupling protein 2 (UCP2) accounted for only ∼20% of OA's excitatory effects and ∼40% of its inhibitory effects. Inhibition of CD36, a fatty acid transporter that can alter cell function independently of intracellular fatty acid metabolism, reduced the effects of OA by up to 45%. Thus OA affects VMN neuronal activity through multiple pathways. In glucosensing neurons, its effects are glucose dependent. This glucose-OA interaction provides a potential mechanism whereby such “metabolic sensing” neurons can respond to differences in the metabolic states associated with fasting and feeding.

scholarly journals Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

2017 ◽  
Vol 32 (6) ◽  
pp. 971-978 ◽  
Author(s):  
Xiaohua Yang ◽  
Patricia Glazebrook ◽  
Geraldine C. Ranasinghe ◽  
Maricela Haghiac ◽  
Virtu Calabuig-Navarro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fatty Acid ◽  
Obese Women ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Transporter Expression

Palmitate movement across red and white muscle membranes of rainbow trout

2004 ◽  
Vol 286 (1) ◽  
pp. R46-R53 ◽  
Author(s):  
Jeff G. Richards ◽  
Arend Bonen ◽  
George J. F. Heigenhauser ◽  
Chris M. Wood
Keyword(s):  
Fatty Acid ◽  
Rainbow Trout ◽  
White Muscle ◽  
Specific Inhibitor ◽  
Fatty Acid Binding ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Fatty Acid Transporter ◽  
Palmitate Uptake ◽  
High Concentrations

We examined the movement of [3H]palmitate across giant sarcolemmal vesicles prepared from red and white muscle of rainbow trout ( Oncorhynchus mykiss). Red and white muscle fatty acid carriers have similar affinities for palmitate (apparent Km = 26 ± 6 and 33 ± 8 nM, respectively); however, red muscle has a higher maximal uptake compared with white muscle ( Vmax = 476 ± 41 vs. 229 ± 23 pmol·mg protein-1·s-1, respectively). Phloretin (250 μM) inhibited palmitate influx in red and white muscle vesicles by ∼40%, HgCl2 (2.5 mM) inhibited palmitate uptake by 20-30%, and the anion-exchange inhibitor DIDS (250 μM) inhibited palmitate influx in red and white muscle vesicles by ∼15 and 30%, respectively. Western blot analysis of red and white muscle vesicles did not detect a mammalian-type fatty acid transporter (FAT); however, preincubation of vesicles with sulfo- N-succinimidyloleate, a specific inhibitor of FAT in rats, reduced palmitate uptake in red and white muscle vesicles by ∼15 and 25%, respectively. A mammalian-type plasma membrane fatty acid-binding protein was identified in trout muscle using Western blotting, but the protein differed in size between red and white muscle. At low concentrations of free palmitate (2.5 nM), addition of high concentrations (111 μM total) of oleate (18:0) caused ∼50% reduction in palmitate uptake by red and white muscle vesicles, but high concentrations (100 μM) of octanoate (8:0) caused no inhibition of uptake. Five days of aerobic swimming at ∼2 body lengths/s and 9 days of chronic cortisol elevation in vivo, both of which stimulate lipid metabolism, had no effect on the rate of palmitate movement in red or white muscle vesicles.

scholarly journals Hyperinsulinemia Enhances Hepatic Expression of the Fatty Acid Transporter Cd36 and Provokes Hepatosteatosis and Hepatic Insulin Resistance

2015 ◽  
Vol 290 (31) ◽  
pp. 19034-19043 ◽  
Author(s):  
Pär Steneberg ◽  
Alexandros G. Sykaras ◽  
Fredrik Backlund ◽  
Jurate Straseviciene ◽  
Ingegerd Söderström ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Insulin Resistance ◽  
Hepatic Expression ◽  
Fatty Acid Transporter ◽  
Acid Transporter

scholarly journals Phenomics reveals a novel putative chloroplast fatty acid transporter in the marine diatom Skeletonema marinoi involved in temperature acclimation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Oskar N. Johansson ◽  
Mats Töpel ◽  
Jenny Egardt ◽  
Matthew I. M. Pinder ◽  
Mats X. Andersson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Temperature Acclimation ◽  
Marine Diatom ◽  
Specific Gene ◽  
Hypothetical Proteins ◽  
Omega 3 ◽  
Fatty Acid Transporter ◽  
Future Value ◽  
Acid Transporter

Abstract Diatoms are the dominant phytoplankton in temperate oceans and coastal regions and yet little is known about the genetic basis underpinning their global success. Here, we address this challenge by developing the first phenomic approach for a diatom, screening a collection of randomly mutagenized but identifiably tagged transformants. Based upon their tolerance to temperature extremes, several compromised mutants were identified revealing genes either stress related or encoding hypothetical proteins of unknown function. We reveal one of these hypothetical proteins is a novel putative chloroplast fatty acid transporter whose loss affects several fatty acids including the two omega-3, long-chain polyunsaturated fatty acids - eicosapentaenoic and docosahexaenoic acid, both of which have medical importance as dietary supplements and industrial significance in aquaculture and biofuels. This mutant phenotype not only provides new insights into the fatty acid biosynthetic pathways in diatoms but also highlights the future value of phenomics for revealing specific gene functions in these ecologically important phytoplankton.

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