Role of acyl-CoAs and acyl-CoA-binding protein in regulation of carbon supply for fatty acid biosynthesis

2000 ◽  
Vol 28 (6) ◽  
pp. 672-674 ◽  
Author(s):  
S. R. Fox ◽  
S. Rawsthorne ◽  
M. J. Hills

Acyl-CoA esters inhibit the plastidial glucose 6-phosphate (Glc-6-P) transporter and the adenylate transporter; the IC50 values for the inhibition by oleoyl-CoA (18:1-CoA) are 200–400 nM and 1–2 μM respectively. The inhibition of either of these processes significantly reduces the flux of carbon from Glc-6-P or from acetate into longchain fatty acids. The effect is dependent on the acyl chain length, e.g. lauryl-CoA is less inhibitory than oleoyl-CoA, causing 34 and 68% inhibition respectively of Glc-6-P uptake after 30 s. The inhibition of Glc-6-P and ATP transport is alleviated by addition of an equivalent concentration of acyl-CoA-binding protein (ACBP) or BSA. Acyl-CoAs do not inhibit pyruvate or glucose transporters. The endogenous concentrations of acyl-CoAs and ACBP are similar during embryo maturation.

Planta ◽  
2010 ◽  
Vol 231 (6) ◽  
pp. 1277-1289 ◽  
Author(s):  
Damián González-Mellado ◽  
Penny von Wettstein-Knowles ◽  
Rafael Garcés ◽  
Enrique Martínez-Force

2019 ◽  
Vol 139 (1) ◽  
pp. 167-175
Author(s):  
Jingyun Gong ◽  
Dong Li ◽  
Xinye Li ◽  
Xuchen Yu ◽  
Yuan Guo ◽  
...  

Langmuir ◽  
2015 ◽  
Vol 31 (17) ◽  
pp. 4906-4915 ◽  
Author(s):  
Sören Stahlberg ◽  
Barbora Školová ◽  
Perunthiruthy K. Madhu ◽  
Alexander Vogel ◽  
Kateřina Vávrová ◽  
...  

2015 ◽  
Vol 22 (4) ◽  
pp. 623-632 ◽  
Author(s):  
Woo-Jae Park ◽  
Ori Brenner ◽  
Aviram Kogot-Levin ◽  
Ann Saada ◽  
Alfred H Merrill ◽  
...  

Pheochromocytoma (PCC) and paraganglioma are rare neuroendocrine tumors of the adrenal medulla and sympathetic and parasympathetic paraganglia, for which mutations in ∼15 disease-associated genes have been identified. We now document the role of an additional gene in mice, the ceramide synthase 2 (CerS2) gene. CerS2, one of six mammalian CerS, synthesizes ceramides with very-long (C22–C24) chains. The CerS2 null mouse has been well characterized and displays lesions in several organs including the liver, lung and the brain. We now demonstrate that changes in the sphingolipid acyl chain profile of the adrenal gland lead to the generation of adrenal medullary tumors. Histological analyses revealed that about half of the CerS2 null mice developed PCC by ∼13 months, and the rest showed signs of medullary hyperplasia. Norepinephrine and normetanephrine levels in the urine were elevated at 7 months of age consistent with the morphological abnormalities found at later ages. Accumulation of ceroid in the X-zone was observed as early as 2 months of age and as a consequence, older mice displayed elevated levels of lysosomal cathepsins, reduced proteasome activity and reduced activity of mitochondrial complex IV by 6 months of age. Together, these findings implicate an additional pathway that can lead to PCC formation, which involves alterations in the sphingolipid acyl chain length. Analysis of the role of sphingolipids in PCC may lead to further understanding of the mechanism by which PCC develops, and might implicate the sphingolipid pathway as a possible novel therapeutic target for this rare tumor.


2020 ◽  
Vol 71 (22) ◽  
pp. 6969-6987
Author(s):  
Naoufal Lakhssassi ◽  
Zhou Zhou ◽  
Shiming Liu ◽  
Sarbottam Piya ◽  
Mallory A Cullen ◽  
...  

Abstract Developing soybean lines with high levels of stearic acid is a primary goal of the soybean industry. Most high-stearic-acid soybeans carry different GmSACPD-C mutated alleles. However, due to the dual role of GmSACPD-C in seeds and nodule development, all derived deleterious GmSACPD-C mutant alleles are of extremely poor agronomic value because of defective nodulation. The soybean stearoyl-acyl carrier protein desaturase (GmSACPD) gene family is composed of five members. Comparative genomics analysis indicated that SACPD genes were duplicated and derived from a common ancestor that is still present in chlorophytic algae. Synteny analysis showed the presence of segment duplications between GmSACPD-A/GmSACPD-B, and GmSACPD-C/GmSACPD-D. GmSACPD-E was not contained in any duplicated segment and may be the result of tandem duplication. We developed a TILLING by Target Capture Sequencing (Tilling-by-Sequencing+) technology, a versatile extension of the conventional TILLING by sequencing, and successfully identified 12, 14, and 18 ethyl methanesulfonate mutants at the GmSACPD-A, GmSACPD-B, and GmSACPD-D genes, respectively. Functional analysis of all identified mutants revealed an unprecedented role of GmSACPD-A, GmSACPD-B, and GmSACPD-D in unsaturated fatty acid biosynthesis without affecting nodule development and structure. This discovery will positively impact the development of high-stearic-acid lines to enhance soybean nutritional value without potential developmental tradeoffs.


2011 ◽  
Vol 79 (10) ◽  
pp. 4201-4209 ◽  
Author(s):  
Julia Bugrysheva ◽  
Barbara J. Froehlich ◽  
Jeffrey A. Freiberg ◽  
June R. Scott

ABSTRACTGenes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogenStreptococcus pyogenes(group A streptococcus [GAS]). We report that in GAS,stkis required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that thestkdeletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence.


2004 ◽  
Vol 383 (3) ◽  
pp. 401-412 ◽  
Author(s):  
Avadhesha SUROLIA ◽  
T. N. C. RAMYA ◽  
V. RAMYA ◽  
Namita SUROLIA

Malaria, a tropical disease caused by Plasmodium sp., has been haunting mankind for ages. Unsuccessful attempts to develop a vaccine, the emergence of resistance against the existing drugs and the increasing mortality rate all call for immediate strategies to treat it. Intense attempts are underway to develop potent analogues of the current antimalarials, as well as a search for novel drug targets in the parasite. The indispensability of apicoplast (plastid) to the survival of the parasite has attracted a lot of attention in the recent past. The present review describes the origin and the essentiality of this relict organelle to the parasite. We also show that among the apicoplast specific pathways, the fatty acid biosynthesis system is an attractive target, because its inhibition decimates the parasite swiftly unlike the ‘delayed death’ phenotype exhibited by the inhibition of the other apicoplast processes. As the enzymes of the fatty acid biosynthesis system are present as discrete entities, unlike those of the host, they are amenable to inhibition without impairing the operation of the host-specific pathway. The present review describes the role of these enzymes, the status of their molecular characterization and the current advancements in the area of developing inhibitors against each of the enzymes of the pathway.


2007 ◽  
Vol 75 (3) ◽  
pp. 1537-1539 ◽  
Author(s):  
Elizabeth M. Fozo ◽  
Kathy Scott-Anne ◽  
Hyun Koo ◽  
Robert G. Quivey

ABSTRACT An insertionally inactivated fabM strain of Streptococcus mutans does not produce unsaturated membrane fatty acids and is acid sensitive (E. M. Fozo and R. G. Quivey, Jr., J. Bacteriol. 186:4152-4158, 2004). In this study, the strain was shown to be poorly transmissible from host to host. Animals directly infected with the fabM strain exhibited fewer and less severe carious lesions than those observed in the wild-type strain.


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