Abstract:
:Serine palmitoyltransferase (SPT) catalyzes the rate-limiting step of condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (3KDS). Here, we report a HPLC-ESI-MS/MS method to directly quantify 3KDS generated by SPT. With this technique, we were able to detect 3KDS at a level comparable to that of dihydrosphingosine in yeast Saccharomyces cerevisiae An in vitro SPT assay measuring the incorporation of deuterated serine into deuterated 3KDS was developed. The results show that SPT kinetics in response to palmitoyl-CoA fit into an allosteric sigmoidal model, suggesting the existence of more than one palmitoyl-CoA binding site on yeast SPT and positive cooperativity between them. Myriocin inhibition of yeast SPT activity was also investigated and we report here, for the first time, an estimated myriocin Ki for yeast SPT of approximately 10 nM. Lastly, we investigated the fate of serine α-proton during SPT reaction. We provide additional evidence to support the proposed mechanism of SPT catalytic activity in regard to proton exchange between the intermediate NH3+ base formed on the active Lys residue with surrounding water. These findings establish the current method as a powerful tool with significant resolution and quantitative power to study SPT activity.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ren J,Snider J,Airola MV,Zhong A,Rana NA,Obeid LM,Hannun YAdoi
10.1194/jlr.D078535subject
Has Abstractpub_date
2018-01-01 00:00:00pages
162-170issue
1eissn
0022-2275issn
1539-7262pii
jlr.D078535journal_volume
59pub_type
杂志文章abstract::Previous studies have shown that antibodies to cubulin, a receptor on the yolk sac that binds high density lipoproteins (HDL) and cobalamin, induce fetal abnormalities. Mice with markedly low concentrations of plasma HDL-cholesterol (HDL-C) give birth to healthy pups, however. To establish whether maternal HDL-C has a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Different batches of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) had varying amounts of contaminants which appeared to affect systematic biological studies. This contaminant was separated by silica gel column chromatography followed by high performance liquid chromatography and identified as 1,3-distearoyl-glyce...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of 3H2O and [14C]mevalonate into digitonin-precipitable sterols with time of...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Changes in the cellularity of various adipose tissues in growing cattle were analyzed. Fifty male cattle were slaughtered between 15 and 65% of mature weight. The whole adipose mass, separated by dissection, was divided into three parts: subcutaneous, intermuscular, and internal adipose tissues. Lipid content, cell si...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatt...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m200312-jlr200
更新日期:2003-01-01 00:00:00
abstract::It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolem...
journal_title:Journal of lipid research
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2000-05-01 00:00:00
abstract::The in vivo total body cholesterol transport of homozygous apoE-deficient (-/-) and control (+/+) mice was evaluated by compartmental analysis of plasma cholesterol decay. Body cholesterol fractional catabolic rates of chow fed mutants were less (-/-, 0.17 +/- 0.02; +/+, 0.51 +/- 0.06 day-1) and body cholesterol conte...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Clock genes respond to external stimuli and exhibit circadian rhythms. This study investigated the expression of clock genes in the small intestine and their contribution in the regulation of nutrient absorption by enterocytes. We examined expression of clock genes and macronutrient transport proteins in the small int...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M900085-JLR200
更新日期:2009-09-01 00:00:00
abstract::The primary structure of apolipoprotein A-II (apoA-II) isolated from the plasma high density lipoprotein (HDL) fraction of the inbred mouse strain BALB/c is described in this work. The complete 78 amino acid protein sequence was determined by proteolytic fragmentation, gas-phase microsequence analysis, and fast atom b...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::EPA and DHA are not biologically equivalent; however, their individual activity on B cells is unknown. We previously reported fish oil enhanced murine B-cell activity in obesity. To distinguish between the effects of EPA and DHA, we studied the ethyl esters of EPA and DHA on murine B-cell function as a function of tim...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M049809
更新日期:2014-07-01 00:00:00
abstract::HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300091-JLR200
更新日期:2003-08-01 00:00:00
abstract::Three aliphatic tricarboxylic acids have been found in rat urine. They have been identified as 6-carboxy-5-undecenedioic acid, 6-carboxy-5-dodecenedoic acid, and 6-carboxy-5-tridecenedioic acid. The carbon skeleton structure was determined by mass spectra of the hydrogenated methyl esters. The double bond position was...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Since spheroidal HDL particles (sHDL) are highly dynamic, molecular dynamics (MD) simulations are useful for obtaining structural models. Here we use MD to simulate sHDL with stoichiometries of reconstituted and circulating particles. The hydrophobic effect during simulations rapidly remodels discoidal HDL containing ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M039206
更新日期:2013-10-01 00:00:00
abstract::Apolipoprotein C-II (apoC-II) plays a critical role in the metabolism of plasma lipoproteins as an activator for lipoprotein lipase. Human apoC-II consists of 79 amino acid residues (pro-apoC-II). A minor fraction is converted to a mature form by cleavage at the site QQDE releasing the 6 amino-terminal residues. We ha...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::The extent and site(s) of inhibition of cholesterol absorption by plant sterols, sitosterol and fucosterol, were studied in rats. The intragastric administration of a single emulsified lipid meal containing 25 mg [3H]cholesterol and 25 mg of either sitosterol or fucosterol inhibited the lymphatic absorption of cholest...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::The proton NMR spectra of the N-methyl choline region of normal and lecithin:cholesterol acyltransferase (LCAT)-deficient lipoproteins and of egg yolk phosphatidylcholine-cholesterol 55:45 (mol %) vesicle mixtures have been examined in the presence and absence of manganous sulfate as a line-broadening reagent. Mangano...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understoo...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M083899
更新日期:2018-08-01 00:00:00
abstract::MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitor...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M033779
更新日期:2013-09-01 00:00:00
abstract::Murine strains susceptible to atherosclerosis provide valuable models to study factors involved in atherogenesis. In some murine models, limited hypercholesterolemia can be achieved and lesions develop primarily in the aortic origin, in the vicinity of the aortic valve. In other models such as LDL receptor-deficient a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Apolipoprotein (apo) E, via its receptor binding domain contained in residues 140-150, mediates hepatic and peripheral tissue binding of cholesterol-rich lipoproteins. Previously, we reported that a synthetic peptide representing a linear tandem repeat of amino acids 141-155, the 141-155 dimer, binds the low density l...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The zinc finger protein ZNF202 is a transcriptional repressor that binds to promoter elements predominantly found in genes involved in lipid metabolism. Here we demonstrate that ZNF202 mRNA expression is inversely correlated with ATP binding cassette A1 (ABCA1), ABCG1, and apolipoprotein E (apoE) in human monocytes. U...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300016-JLR200
更新日期:2003-05-01 00:00:00
abstract::Sterol 27-hydroxylase, the mitochondrial enzyme that catalyzes the first step in oxidation of the sterol side chain in hepatic bile acid synthesis, also catalyzes the synthesis of 27-hydroxycholesterol from cholesterol. We have developed a high performance liquid chromatography (HPLC) assay for this enzyme, using eith...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Nucleoredoxin (NRX) is a member of the thioredoxin family of proteins that controls redox homeostasis in cell. Redox homeostasis is a well-known regulator of cell differentiation into various tissue types. We found that NRX expression levels were higher in white adipose tissue of obese ob/ob mice and increased in the ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M054056
更新日期:2015-02-01 00:00:00
abstract::The kinetics of lecithin exchange between native lipoproteins was characterized for individual molecular species of lecithins of rat mesenteric lymph chylomicrons and rat plasma HDL. Studies were performed in the absence of lipid transfer proteins. Donor (chylomicrons) and acceptor (HDL) particles were present in rati...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M022673
更新日期:2012-05-01 00:00:00
abstract::Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m100254-jlr200
更新日期:2002-07-01 00:00:00
abstract::There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this "HDL hypothesi...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R001610
更新日期:2010-08-01 00:00:00
abstract::The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by nor...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Ceramides (Cers) with ultralong (∼32-carbon) chains and ω-esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ∼10 mol%; diminished concentrations, along with altered or miss...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.RA119000420
更新日期:2020-02-01 00:00:00
abstract::Human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) is essential for the intralysosomal metabolism of cholesteryl esters and triglycerides taken up by receptor-mediated endocytosis of lipoprotein particles. The key role of the enzyme in intracellular lipid homeostasis is illustrated by two lysosomal storage...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00