The effect of altered sphingolipid acyl chain length on various disease models

2015 ◽  
Vol 396 (6-7) ◽  
pp. 693-705 ◽  
Author(s):  
Woo-Jae Park ◽  
Joo-Won Park
Keyword(s):  
Chain Length ◽  
De Novo ◽  
Case Reports ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Sphingolipid Metabolism ◽  
Lipid Mediator ◽  
Disease Models ◽  
Acyl Chain Length ◽  
Sphingosine 1 Phosphate

Abstract Sphingolipids have emerged as an important lipid mediator in intracellular signalling and metabolism. Ceramide, which is central to sphingolipid metabolism, is generated either via a de novo pathway, by attaching fatty acyl CoA to a long-chain base, or via a salvage pathway, by degrading pre-existing sphingolipids. As a ‘sphingolipid rheostat’ has been proposed, the balance between ceramide and sphingosine-1-phosphate has been the object of considerable attention. Ceramide has recently been reported to have a different function depending on its acyl chain length: six ceramide synthases (CerS) determine the specific ceramide acyl chain length in mammals. All CerS-deficient mice generated to date show that sphingolipids with defined acyl chain lengths play distinct pathophysiological roles in disease models. This review describes recent advances in understanding the associations of CerS with various diseases and includes clinical case reports.

Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and SimulatedIn VitroDigestion Model

2015 ◽  
Vol 81 (2) ◽  
pp. C317-C323
Author(s):  
Jin F. Qi ◽  
Cai H. Jia ◽  
Jung A. Shin ◽  
Jeong M. Woo ◽  
Xiang Y. Wang ◽  
...  
Keyword(s):  
Chain Length ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Lipid Digestion ◽  
Acyl Chain Length ◽  
Ph Stat

scholarly journals Ceramide synthases at the centre of sphingolipid metabolism and biology

2012 ◽  
Vol 441 (3) ◽  
pp. 789-802 ◽  
Author(s):  
Thomas D. Mullen ◽  
Yusuf A. Hannun ◽  
Lina M. Obeid
Keyword(s):  
Cell Death ◽  
De Novo ◽  
Acyl Chain ◽  
Sphingolipid Metabolism ◽  
Sphingoid Base ◽  
Salvage Pathway ◽  
Organismal Biology ◽  
Acyl Chain Length ◽  
Specific Manner ◽  
Ceramide Synthases

Sphingolipid metabolism in metazoan cells consists of a complex interconnected web of numerous enzymes, metabolites and modes of regulation. At the centre of sphingolipid metabolism reside CerSs (ceramide synthases), a group of enzymes that catalyse the formation of ceramides from sphingoid base and acyl-CoA substrates. From a metabolic perspective, these enzymes occupy a unique niche in that they simultaneously regulate de novo sphingolipid synthesis and the recycling of free sphingosine produced from the degradation of pre-formed sphingolipids (salvage pathway). Six mammalian CerSs (CerS1–CerS6) have been identified. Unique characteristics have been described for each of these enzymes, but perhaps the most notable is the ability of individual CerS isoforms to produce ceramides with characteristic acyl-chain distributions. Through this control of acyl-chain length and perhaps in a compartment-specific manner, CerSs appear to regulate multiple aspects of sphingolipid-mediated cell and organismal biology. In the present review, we discuss the function of CerSs as critical regulators of sphingolipid metabolism, highlight their unique characteristics and explore the emerging roles of CerSs in regulating programmed cell death, cancer and many other aspects of biology.

Lipid profiling of human diabetic myocardium reveals differences in triglyceride fatty acyl chain length and degree of saturation

2020 ◽  
Vol 320 ◽  
pp. 106-111
Author(s):  
Elias Björnson ◽  
Ylva Östlund ◽  
Marcus Ståhlman ◽  
Martin Adiels ◽  
Elmir Omerovic ◽  
...  
Keyword(s):  
Chain Length ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Degree Of Saturation ◽  
Fatty Acyl Chain ◽  
Lipid Profiling ◽  
Acyl Chain Length ◽  
Diabetic Myocardium

scholarly journals Dependence of fatty acyl chain length on the property of phase separation of GM3/DPPC multilamellar vesicles

2001 ◽  
Vol 41 (supplement) ◽  
pp. S128
Author(s):  
S. Matsuoka ◽  
M. Akiyama ◽  
H. Yamada ◽  
K. Tsuchihashi ◽  
S. Gasa
Keyword(s):  
Phase Separation ◽  
Chain Length ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Multilamellar Vesicles ◽  
Acyl Chain Length

scholarly journals The elongation of exogenous fatty acids and the control of phospholipid acyl chain length in Micrococcus cryophilus

1980 ◽  
Vol 188 (3) ◽  
pp. 585-592 ◽  
Author(s):  
S P Sandercock ◽  
N J Russell
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Chain Length ◽  
De Novo ◽  
Acyl Chain ◽  
Psychrophilic Bacterium ◽  
Fatty Acid Elongation ◽  
Acyl Chain Length ◽  
Acyl Chains ◽  
Phospholipid Acyl Chain

The synthesis of fatty acids de novo from acetate and the elongation of exogenous satuated fatty acids (C12-C18) by the psychrophilic bacterium Micrococcus cryophilus (A.T.C.C. 15174) grown at 1 or 20 degrees C was investigated. M. cryophilus normally contains only C16 and C18 acyl chains in its phospholipids, and the C18/C16 ratio is altered by changes in growth temperature. The bacterium was shown to regulate strictly its phospholipid acyl chain length and to be capable of directly elongating myristate and palmitate, and possibly laurate, to a mixture of C16 and C18 acyl chains. Retroconversion of stearate into palmitate also occurred. Fatty acid elongation could be distinguished from fatty acid synthesis de novo by the greater sensitivity of fatty acid elongation to inhibition by NaAsO2 under conditions when the supply of ATP and reduced nicotinamide nucleotides was not limiting. It is suggested that phospholipid acyl chain length may be controlled by a membrane-bound elongase enzyme, which interconverts C16 and C18 fatty acids via a C14 intermediate; the activity of the enzyme could be regulated by membrane lipid fluidity.

Ketoacyl synthase domain is a major determinant for fatty acyl chain length in Saccharomyces cerevisiae

2013 ◽  
Vol 195 (12) ◽  
pp. 843-852 ◽  
Author(s):  
Juthaporn Sangwallek ◽  
Yoshinobu Kaneko ◽  
Minetaka Sugiyama ◽  
Hisayo Ono ◽  
Takeshi Bamba ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chain Length ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Major Determinant ◽  
Fatty Acyl Chain ◽  
Acyl Chain Length ◽  
Ketoacyl Synthase

scholarly journals Acyl-chain specificity of human milk bile-salt-activated lipase

1991 ◽  
Vol 279 (1) ◽  
pp. 297-302 ◽  
Author(s):  
C S Wang
Keyword(s):  
Human Milk ◽  
Bile Salt ◽  
Chain Length ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Acyl Chain Length ◽  
Enzyme Substrate ◽  
Consistent Trend ◽  
Kinetics Of ◽  
Long Chain

In order to probe the active-site structure of human milk bile-salt-activated lipase (BAL), the kinetics of the BAL-catalysed reaction were studied using monoesters as substrates. Among the fatty acyl chains, ranging from C8 to C16 of monoacylglycerols in a single equimolar assay mixture, there was a consistent trend of increased reactivity with decreased fatty-acyl-chain length for both the basal and taurocholate-stimulated activities of BAL. In addition, the detection of hydrolysis of long-chain monoacylglycerols in the absence of bile salt indicates that it is possible for the long-chain fatty acid monoester to form an enzyme-substrate complex with the basal form of BAL. I further examined the reaction kinetics of BAL with water-soluble short-chain esters of p-nitrophenol. The results indicated that there is a consistent trend towards a decreased Michaelis-Menten constant with increased acyl-chain length. Therefore it was concluded that the decreased reactivity with increased acyl-chain length of acylglycerols is probably not a consequence of the lowered affinity of the substrate for the enzyme. The fact that butyrate ester has the optimum acyl chain to be a substrate of BAL can be attributed to its acyl-chain length being long enough for interaction with the active centre of BAL and short enough to provide adequate positioning of the ester bond for transition state complex formation. The calculated free energy of BAL catalysis based on the derived kinetic parameters provides additional insight into the effect on the enzyme-substrate interaction of increasing the number of methylene groups in the acyl chain of substrates.

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