scholarly journals A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Huanhu Zhu ◽  
Huali Shen ◽  
Aileen K Sewell ◽  
Marina Kniazeva ◽  
Min Han
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Growth And Development ◽  
Postembryonic Development ◽  
Chain Fatty Acid ◽  
Metabolic Status ◽  
Animal Development ◽  
Branched Chain

Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR.

Properties of Acetate Kinase Isozymes and a Branched-Chain Fatty Acid Kinase from a Spirochete

1982 ◽  
Vol 152 (1) ◽  
pp. 246-254
Author(s):  
Caroline S. Harwood ◽  
Ercole Canale-Parola
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Molecular Weight ◽  
Fatty Acid ◽  
Branched Chain Amino Acids ◽  
Chain Fatty Acid ◽  
Acetate Kinase ◽  
Nucleoside Triphosphate ◽  
Branched Chain ◽  
Chain Fatty Acids

Spirochete MA-2, which is anaerobic, ferments glucose, forming acetate as a major product. The spirochete also ferments (but does not utilize as growth substrates) small amounts of l -leucine, l -isoleucine, and l -valine, forming the branched-chain fatty acids isovalerate, 2-methylbutyrate, and isobutyrate, respectively, as end products. Energy generated through the fermentation of these amino acids is utilized to prolong cell survival under conditions of growth substrate starvation. A branched-chain fatty acid kinase and two acetate kinase isozymes were resolved from spirochete MA-2 cell extracts. Kinase activity was followed by measuring the formation of acyl phosphate from fatty acid and ATP. The branched-chain fatty acid kinase was active with isobutyrate, 2-methylbutyrate, isovalerate, butyrate, valerate, or propionate as a substrate but not with acetate as a substrate. The acetate kinase isozymes were active with acetate and propionate as substrates but not with longer-chain fatty acids as substrates. The acetate kinase isozymes and the branched-chain fatty acid kinase differed in nucleoside triphosphate and cation specificities. Each acetate kinase isozyme had an apparent molecular weight of approximately 125,000, whereas the branched-chain fatty acid kinase had a molecular weight of approximately 76,000. These results show that spirochete MA-2 synthesizes a branched-chain fatty acid kinase specific for leucine, isoleucine, and valine fermentation. It is likely that a phosphate branched-chain amino acids is also synthesized by spirochete MA-2. Thus, in spirochete MA-2, physiological mechanisms have evolved which serve specifically to generate maintenance energy from branched-chain amino acids.

Biosynthesis of Branched-chain Fatty Acid inBacilli: FabD (malonyl-CoA:ACP transacylase) Is Not Essential forIn VitroBiosynthesis of Branched-chain Fatty Acids

2003 ◽  
Vol 67 (10) ◽  
pp. 2106-2114 ◽  
Author(s):  
Hirosuke OKU ◽  
Naoya FUTAMORI ◽  
Kenichi MASUDA ◽  
Yumiko SHIMABUKURO ◽  
Tomoyo OMINE ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

scholarly journals Exogenous Isoleucine and Fatty Acid Shortening Ensure the High Content of Anteiso-C15:0 Fatty Acid Required for Low-Temperature Growth of Listeria monocytogenes

2005 ◽  
Vol 71 (12) ◽  
pp. 8002-8007 ◽  
Author(s):  
Kun Zhu ◽  
Xiang Ding ◽  
Mudcharee Julotok ◽  
Brian J. Wilkinson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Listeria Monocytogenes ◽  
Low Temperature ◽  
Fatty Acid Profile ◽  
Acyl Carrier Protein ◽  
Critical Role ◽  
Chain Fatty Acid ◽  
Fatty Acid Chain ◽  
Branched Chain

ABSTRACT Previous studies have demonstrated that the branched-chain fatty acid anteiso-C15:0 plays a critical role in the growth of Listeria monocytogenes at low temperatures by ensuring sufficient membrane fluidity. Studies utilizing a chemically defined minimal medium revealed that the anteiso fatty acid precursor isoleucine largely determined the fatty acid profile and fatty acid response of the organism to lowered growth temperature. When isoleucine was sufficient, the fatty acid profile was very uniform, with anteiso fatty acids comprising up to 95% of total fatty acid, and the major fatty acid adjustment to low temperature was fatty acid chain shortening, which resulted in an increase of anteiso-C15:0 solely at the expense of anteiso-C17:0. When isoleucine was not supplied, the fatty acid profile became more complex and was readily modified by leucine, which resulted in a significant increase of corresponding iso fatty acids and an inability to grow at 10°C. Under this condition, the increase of anteiso-C15:0 at low temperature resulted from the combined effect of increasing the anteiso:iso ratio and chain shortening. A branched-chain α-keto acid dehydrogenase-defective strain largely lost the ability to increase the anteiso:iso ratio. Cerulenin, an inhibitor of β-ketoacyl-acyl carrier protein synthase (FabF), induced a similar fatty acid chain shortening as low temperature did. We propose that the anteiso precursor preferences of enzymes in the branched-chain fatty acid biosynthesis pathway ensure a high production of anteiso fatty acids, and cold-regulated chain shortening results in a further increase of anteiso-C15:0 at the expense of anteiso-C17:0.

scholarly journals Monomethyl branched-chain fatty acid mediates amino acid sensing by mTORC1

2020 ◽  
Author(s):  
Mengnan Zhu ◽  
Fukang Teng ◽  
Na Li ◽  
Li Zhang ◽  
Jing Shao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Protein Translation ◽  
Postembryonic Development ◽  
Chain Fatty Acid ◽  
Nutrient Sensing ◽  
Acid Deficiency ◽  
Branched Chain ◽  
Amino Acid Sensing ◽  
The Impact

AbstractAnimals have developed various nutrient-sensing mechanisms for survival under fluctuating environments. Although extensive cultured cell-based analyses have discovered diverse mediators of amino acid sensing by mTOR, studies using animal models to illustrate intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid, and downstream glycosphingolipid, that critically mediate overall amino acid sensing by intestinal and neuronal mTORC1 that, in turn, regulates postembryonic development partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may be conserved in mammals. This study uncovers an unexpected amino acid sensing mechanism mediated by a lipid biosynthesis pathway.

scholarly journals Regulatory effects of fatty acids on decarboxylation of leucine and 4-methyl-2-oxopentanoate in the perfused rat heart

1984 ◽  
Vol 221 (3) ◽  
pp. 593-599 ◽  
Author(s):  
D B Buxton ◽  
L L Barron ◽  
M K Taylor ◽  
M S Olson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Heart ◽  
Chain Fatty Acid ◽  
Oxidative Decarboxylation ◽  
Enzyme Complex ◽  
Acid Dehydrogenase ◽  
Dehydrogenase Reaction ◽  
Regulatory Effects ◽  
Branched Chain

The regulatory effects of fatty acids on the oxidative decarboxylation of leucine and 4-methyl-2-oxopentanoate were investigated in the isolated rat heart. Infusion of the long-chain fatty acid palmitate resulted in both an inactivation of the branched-chain 2-oxo acid dehydrogenase and an inhibition of the measured metabolic flux through this enzyme complex. Pyruvate addition also caused both an inactivation and an inhibition of the flux through the complex. On the other hand, the medium-chain fatty acid octanoate caused an activation of and a stimulation of flux through the branched-chain 2-oxo acid dehydrogenase when the perfusion conditions before octanoate addition maintained the enzyme complex in its inactive state. When the enzyme complex was activated before octanoate infusion, this fatty acid caused a significant inhibition of the flux through the branched-chain 2-oxo acid dehydrogenase reaction. Inclusion of glucose in the perfusion medium prevented the octanoate-mediated activation of the branched-chain 2-oxo acid dehydrogenase.

Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts

2002 ◽  
Vol 283 (3) ◽  
pp. C688-C703 ◽  
Author(s):  
Barbara P. Atshaves ◽  
Stephen M. Storey ◽  
Anca Petrescu ◽  
Cynthia C. Greenberg ◽  
Olga I. Lyuksyutova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Lipid Accumulation ◽  
Phytanic Acid ◽  
Chain Fatty Acid ◽  
Fatty Acid Binding Proteins ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Branched Chain

High levels of saturated, branched-chain fatty acids are deleterious to cells and animals, resulting in lipid accumulation and cytotoxicity. Although fatty acid binding proteins (FABPs) are thought to be protective, this hypothesis has not previously been examined. Phytanic acid (branched chain, 16-carbon backbone) induced lipid accumulation in L cell fibroblasts similar to that observed with palmitic acid (unbranched, C16): triacylglycerol ≫ free fatty acid > cholesterol > cholesteryl ester ≫ phospholipid. Although expression of sterol carrier protein (SCP)-2, SCP-x, or liver FABP (L-FABP) in transfected L cells reduced [3H]phytanic acid uptake (57–87%) and lipid accumulation (21–27%), nevertheless [3H]phytanic acid oxidation was inhibited (74–100%) and phytanic acid toxicity was enhanced in the order L-FABP ≫ SCP-x > SCP-2. These effects differed markedly from those of [3H]palmitic acid, whose uptake, oxidation, and induction of lipid accumulation were not reduced by L-FABP, SCP-2, or SCP-x expression. Furthermore, these proteins did not enhance the cytotoxicity of palmitic acid. In summary, intracellular FABPs reduce lipid accumulation induced by high levels of branched-chain but not straight-chain saturated fatty acids. These beneficial effects were offset by inhibition of branched-chain fatty acid oxidation that correlated with the enhanced toxicity of high levels of branched-chain fatty acid.

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