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1.
Two groups of male Wistar rats were fed normal (i.e., 18%) and protein-free diets, respectively, for 7 weeks. In vivo incorporation
of [1-14C] acetate into palmitic, stearic, oleic, and arachidonic acids by the liver was reduced in the protein-deficient rats. In
vitro incubation of liver microsomes with labeled palmitate or linoleate revealed no change in the specific activities of
chain elongating or desaturating enzymes. Protein deficiency resulted in a decrease in specific activity of short chain acyl-CoA
synthetase and in total CoA, accompanied by the virtual disappearance of acyl-CoA and an increase in free CoA. Furthermore,
there was less microsomal fatty acid synthetase and mitochondrial β-hydroxybutyrate dehydrogenase activity. These results
are discussed in relation to fatty acid synthesis and the changes in liver fatty acid composition. 相似文献
2.
Low rates of triacylglycerol (TAG) biosynthesis were observed in cell-free extracts ofCandida curvata, but rates were increased up to 10-fold by adding either α- or β-cyclodextrins. Spheroplasts, whole or gently disrupted,
had higher rates of incorporation of both [U-14C]glycerol 3-phosphate or [1-14C]oleate into triacylglycerol and the intermediates of its biosynthesis: lysophosphatic acid, phosphatidic acid and diacylglycerol.
Fatty acyl-CoA synthetase was highest with palmitate, oleate and linoleate but was some 6- to 8-fold lower with stearate.
Stearate and stearoyl-CoA were poorly incorporated into lipids. Subcellular fractionation of the spheroplasts into mitochondrial,
microsomal, lipid bodies and supernatant fractions diminished the rates of14C incorporation of oleate into triacylglycerol. By comparing the relative specific activities for each activity in each fraction,
the fatty acyl-CoA synthetase activity appeared mainly in the lipid bodies, and that for phosphatidic acid formation was mainly
in the mitochondrion; other activities were too weak and too dispersed for accurate assessment of their location. Recombining
all the subcellular fractions restored triacylglycerol synthesizing activity. Omitting any single fraction from the mixture
did not result in restoration of triacylglycerol synthesizing activity. Starvation of the yeast, which leads to utilization
of the endogenous lipid reserves, stimulated fatty acyl-CoA synthetase activity, but diminished phosphatidic acid and triacylglycerol
biosynthesis indicating probable induction of β-oxidation in the peroxisomes and repression of lipid biosynthesis. 相似文献
3.
Streptozotocin-induced diabetes significantly decreased rat liver microsomal long-chain fatty acyl-CoA (LCA-CoA) hydrolase.
The decrease was observed using either palmitoyl-CoA (35 per cent, p<0.01) or oleoyl-CoA (23 per cent, p<0.01) as the substrate
for the enzyme. Under the same conditions, diabetes did not significantly alter activity of LCA-CoA synthetase. Daily subcutaneous
injections of protamine zinc insulin (10–12 units/day) into the diabetic rats returned their blood glucose to normal but only
partially corrected the LCA-CoA hydrolase activity and did not effect LCA-CoA synthetase activity. The decreased LCA-CoA hydrolase
and the unchanged LCA-CoA synthetase activities in the diabetic rat liver were interpreted as factors that may contribute
to elevation of fatty acyl-CoA levels in the diabetic liver. 相似文献
4.
The effect of Triton X-100 on the activities and apparent molecular size of fatty acyl-CoA synthetase, solubilized and partially
purified from rat liver microsomes, was studied. In the presence of Triton X-100, the activity for lignoceroyl-CoA synthesis
was decreased, but activity was restored when the detergent was removed. The appearance and disappearance of lignoceroyl-CoA
synthesis appeared related to the size, of the aggregated from of the enzyme. On the other hand, activity for palmitoyl-CoA
synthesis was not significantly affected by the detergent. Because available evidence suggests that both fatty acids are converted
to CoA esters by the same enzyme, it seems likely that the substrate specificity of the enzyme is influenced by changes in
the aggregation state branes may determine the substrate specificity of acyl-CoA synthetase. 相似文献
5.
Enzymes catalyzing the first and last steps in cocoa butter biosynthesis were studied in microsomal preparations from developing
cocoa seeds. Both the acyl-CoA:sn-glycerol-3-phosphate 0-acyltransferase (EC 2.3.1.15) and the acyl-CoA:1,2-diacylglycerol
0-acyltransferase (EC 2.3.1.20) showed broad specificity for three fatty acid donors (palmitoyl-CoA, stearoyl-CoA and oleoyl-CoA),
but the relative amounts of incorporation of these fatty acids into lysophosphatidic acid and triacylglycerol were influenced
by temperature of incubation. The selectivities of the two acyltransferases for saturated vs unsaturated acyl-CoA’s also were
investigated over a range of temperatures. The data indicate that, in general, the ratio of saturated to unsaturated fatty
acids incorporated into glycerol esters increases with increasing temperature of incubation, consistent with the hypothesis
that temperature effects on these enzymes contribute to the phenomenon of “soft” cocoa butter, i.e., that cocoa butter obtained
from seeds grown in cooler climates has a lower melting point than that prepared from seeds grown in warmer climates. 相似文献
6.
Translocation of long-chain acyl-coenzyme A hydrolase from the microsomal fraction to the cytosolic fraction was promoted
in cell-free extracts of rat liver by palmitic acid, oleic acid, tetradecylthioacetic acid, and tetradecylthiopropionic acid,
and by their CoA esters. The CoA esters were more effective than the non-esterified acids in the translocation of the enzyme.
Treatment of normolipidemic rats with sulfur-substituted non-β-oxidizable fatty acid analogues resulted in a transitory increase
in hepatic concentration of long-chain acyl-CoA. Longer feeding times almost normalized the hepatic long-chain acyl-CoA content.
Microsomal long-chain acyl-CoA hydrolase activity was inhibited, whereas the activity of the cytosolic form was stimulated.
The rise in enzyme activity coincided with a reduction in liver content of triglyceride and an increase in hepatic phospholipid
content. The results suggest that the activity of long-chain acyl-CoA hydrolase in the cytosol may control the amount of acyl-CoA
thioesters in the liver. Esterified and non-esterified fatty acids causedin vitro translocation of phosphatidate phosphohydrolase and cytidine 5′-triphosphate (CTP):phosphocholine cytidylyltransferase from
the cytosolic fraction to the microsomal fraction. However, the translocation of these two enzyme systems was not obtainedin vivo. The activity of phosphatidate phosphohydrolase decreased in microsomal and cytosolic fractions while the activity of cytidylyltransferase
in these fractions increased. The activities of soluble phosphatidate phosphohydrolase and long-chain acyl-CoA hydrolase appeared
to be inversely correlated. The results imply that in cytoplasm, long-chain acyl-CoA hydrolase may compete with the biosynthetic
enzymes for the acyl-CoA substrate, thus influencing the rate of lipid synthesis. The reduced hepatic triglyceride content
observed in tetradecylthioacetic acid-treated rats is probably due to reduced triglyceride synthesis, which is mediated by
an inhibition of phosphatidate phosphohydrolase accompanied with translocation and stimulation of long-chain acyl-CoA hydrolase.
Development of fatty liver as an effect of tetradecylthiopropionic acid is probably due to accelerated triglyceride biosynthesis,
which is mediated by a stimulation of phosphatidate phosphohydrolase and a decrease in cytosolic palmitoyl-CoA hydrolase activity. 相似文献
7.
Acyl-CoA synthetase activity with various long chain fatty acid substrates was measured in microsomes from rat testes, isolated
spermatids and testes of hypophysectomized adult rats, using reversed-phase high performance liquid chromatography (HPLC).
The spectrophotometric HPLC method produced results comparable to those of parallel radiometric assays and was highly specific
for acyl-CoA products. At optimal pH and cofactor concentrations, specific activity from whole testis was similar for 18∶1,
20∶4 and 22∶5 but somewhat lower for 16∶0 over the substrate range 0.01–3.2 mM. Activity from spermatids or from testes of
hypophysectomized rats was much lower with 22∶5 than with 18∶1 or 20∶4, whereas activities with 18∶1 and 20∶4 were similar
at all substrate concentrations. All substrates exhibited Michaelis-Menten type saturation kinetics and linear Lineweaver-Burke
plots at lower substrate concentrations but inhibited activity at higher concentrations. Apparent values of KM for 16∶0, 18∶1 and 20∶4 were more than twice that of 22∶5, whereas both observed and calculated maximum velocities were similar
for the four fatty acids. Differences in pseudokinetic parameters and differential expression of the testicular acyl-CoA synthetase
activities with different fatty acids suggest the presence of multiple enzymes, at least one of which may be hormonally regulated. 相似文献
8.
Narasimhan Ramarathnam Toshihiko Osawa Mitsuo Namiki Shunro Kawakishi 《Journal of the American Oil Chemists' Society》1989,66(1):105-108
Accelerated aging effects, induced by y irradiation, were investigated on the fatty acid composition of lipids and on the
content of endogenous antioxidants of four Indica and four Japonica rice seeds with and without intact hull. While the linoleic
acid content of the phospholipids decreased gradually with the increase in irradiation doses, there was a corresponding increase
in the linoleic acid content of the free fatty acids. Such changes were drastic, especially in the case of Japonica rice seeds
irradiated without intact hull. However, the neutral lipids were found to be resistant to γ irradiation.
The α-tocopherol content was found to decrease (markedly) in rice seeds irradiated with or without hull, especially in the
Japonica rice seeds. At a dose of 15 kGy only traces of a-tocopherol could be detected in Japonica and Indica rice seeds irradiated
with and without intact hull. Oryzanol, a relatively weaker anti-oxidant, was found to be more resistant to oxidative damage
than a-tocopherol. At 15 kGy, the oryzanol content ranged from 59 μg to 170 μg/g lipid in rice seeds irradiated with intact
hull, while the corresponding value for rice seeds irradiated without hull was 52 μg to 153 μg/g lipid.
The overall susceptibility to oxidative damage was less in Indica rice seeds, indicating that the antioxidative defense system
offered better protection in overcoming oxidative stress in Indica rice hull than in Japonica rice hull. 相似文献
9.
Altered Metabolic Flexibility in Inherited Metabolic Diseases of Mitochondrial Fatty Acid Metabolism
Sara Tucci Khaled Ibrahim Alatibi Zeinab Wehbe 《International journal of molecular sciences》2021,22(7)
In general, metabolic flexibility refers to an organism’s capacity to adapt to metabolic changes due to differing energy demands. The aim of this work is to summarize and discuss recent findings regarding variables that modulate energy regulation in two different pathways of mitochondrial fatty metabolism: β-oxidation and fatty acid biosynthesis. We focus specifically on two diseases: very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and malonyl-CoA synthetase deficiency (acyl-CoA synthetase family member 3 (ACSF3)) deficiency, which are both characterized by alterations in metabolic flexibility. On the one hand, in a mouse model of VLCAD-deficient (VLCAD−/−) mice, the white skeletal muscle undergoes metabolic and morphologic transdifferentiation towards glycolytic muscle fiber types via the up-regulation of mitochondrial fatty acid biosynthesis (mtFAS). On the other hand, in ACSF3-deficient patients, fibroblasts show impaired mitochondrial respiration, reduced lipoylation, and reduced glycolytic flux, which are compensated for by an increased β-oxidation rate and the use of anaplerotic amino acids to address the energy needs. Here, we discuss a possible co-regulation by mtFAS and β-oxidation in the maintenance of energy homeostasis. 相似文献
10.
The conversion of 2-acyl-sn-glycero-3-phosphorylinositol into phosphatidylinositol via acyl-CoA: 2-acyl-sn-glycero-3-phosphorylinositol acyltransferase activity was found to occur in rat liver microsomes. Over a wide range of conditions,
stearic acid was preferred over palmitate by the acyltransferase when these acids were presented in mixtures as acyl-CoA derivatives.
The potential importance of this enzyme activity for the entry of stearic acid into the 1-position of hepatic phosphatidylinositol
is further supported by its greater preference for stearate relative to the acyl-CoA: 2-acyl-sn-glycero-3-phosphorylcholine acyltransferase under certain assay conditions. 相似文献
11.
Serina L. Robinson Dr. James K. Christenson Prof. Dr. Jack E. Richman Dominick J. Jenkins Dr. João Neres Dallas R. Fonseca Prof. Dr. Courtney C. Aldrich Prof. Dr. Lawrence P. Wackett 《Chembiochem : a European journal of chemical biology》2019,20(13):1701-1711
Enzyme-catalyzed β-lactone formation from β-hydroxy acids is a crucial step in bacterial biosynthesis of β-lactone natural products and membrane hydrocarbons. We developed a novel, continuous assay for β-lactone synthetase activity using synthetic β-hydroxy acid substrates with alkene or alkyne moieties. β-Lactone formation is followed by rapid decarboxylation to form a conjugated triene chromophore for real-time evaluation by UV/Vis spectroscopy. The assay was used to determine steady-state kinetics of a long-chain β-lactone synthetase, OleC, from the plant pathogen Xanthomonas campestris. Site-directed mutagenesis was used to test the involvement of conserved active site residues in Mg2+ and ATP binding. A previous report suggested OleC adenylated the substrate hydroxy group. Here we present several lines of evidence, including hydroxylamine trapping of the AMP intermediate, to demonstrate the substrate carboxyl group is adenylated prior to making the β-lactone final product. A panel of nine substrate analogues were used to investigate the substrate specificity of X. campestris OleC by HPLC and GC-MS. Stereoisomers of 2-hexyl-3hydroxyoctanoic acid were synthesized and OleC preferred the (2R,3S) diastereomer consistent with the stereo-preference of upstream and downstream pathway enzymes. This biochemical knowledge was used to guide phylogenetic analysis of the β-lactone synthetases to map their functional diversity within the acyl-CoA synthetase, NRPS adenylation domain, and luciferase superfamily. 相似文献
12.
A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids 总被引:6,自引:0,他引:6
Fatty acids are the main structural and energy sources of the human body. Within the organism, they are presented to cells
as fatty acid: albumin complexes. Dissociation from albumin represents the first step of the cellular uptake process, involving
membrane proteins with high affinity for fatty acids, e.g., fatty acid translocase (FAT/CD 36) or the membrane fatty acid-binding
protein (FABPpm). According to the thus created transmembrane concentration gradient, uncharged fatty acids can flip-flop from the outer
leaflet across the phospholipid bilayer. At the cytosolic surface of the plasma membrane, fatty acids can associate with the
cytosolic FABP (FABP
c
) or with caveolin-1. Caveolins are constituents of caveolae, which are proposed to serve as lipid delivery vehicles for subcellular
organelles. It is not known whether protein (FABP
c
)- and lipid (caveolae)-mediated intracellular trafficking of fatty acids operates in conjunction, or in parallel. Channeling
fatty acids to the different metabolic pathways requires activation to acyl-CoA. For this process, the family of fatty acid
transport proteins (FATP 1-5/6) might be relevant because they have been shown to possess acyl-CoA synthetase activity. Their
variable N-terminal signaling sequences suggest that they might be targeted to specific organelles by anchoring in the phospholipid
bilayer of the different subcellular membranes. At the highly conserved cytosolic AMP-binding site of FATP, fatty acids are
activated to acyl-CoA for subsequent metabolic disposition by specific organelles. Overall, fatty acid uptake represents a
continuous flow involving the following: dissociation from albumin by membrane proteins with high affinity for fatty acids;
passive flip-flop across the phospholipid bilayer; binding to FABP
c
and caveolin-1 at the cytosolic plasma membrane; and intracellular trafficking via FABP
c
and/or caveolae to sites of metabolic disposition. The uptake process is terminated after activation to acyl-CoA by the members
of the FATP family targeted intracellularly to different organelles. 相似文献
13.
Burnham BS Sood A Tomasz J Powell WJ Spielvogel BF Chen SY Hall IH 《Metal-Based Drugs》1996,3(4):173-183
The boronated nucleosides with varying bases and sugar moieties were shown to be potent hypolipidemic agents in rodents. The 3'- aminocynaoborane dideoxythymidine derivative caused reductions in serum cholesterol and triglyceride levels, tissue lipids, VLDL and LDL cholesterol levels while elevating HDL cholesterol levels in rodents. The agents suppressed rat hepatic acetyl CoA synthetase, HMG-CoA reductase, acyl-CoA cholesterol acyl transferase, phosphatidylate phosphohydrolase and lipoprotein lipase activities while elevating cholesterol-7alpha-hydroxylase activity from 25 to 100 muM. 相似文献
14.
Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue 总被引:3,自引:0,他引:3
Zivart Yasruel Katherine Cianflone Allan D. Sniderman Mark Rosenbloom Mark Walsh Miguel A. Rodriguez 《Lipids》1991,26(7):495-499
Acylation stimulating protein (ASP) is a 14 kDa plasma protein which causesin vitro triacylglycerol synthesis in human adipocytes and fibroblasts to increase substantially. ASP was found to stimulate human
adipose tissue microsomal glycerophosphate acyltransferase and diacylglycerol acyltransferase activities by 23% and 90%, respectively.
However, phosphatidate phosphohydrolase activity showed no increase in activity, nor did microsomal acyl-CoA synthetase activity.
Moreover, ASP did not decrease the apparent Km of diacylglycerol acyltransferase (DGAT), but rather increased its apparent Vmax suggesting direct interaction of ASP with DGAT. 相似文献
15.
Sangkyu Park Min Ji Choi Jong Yeol Lee Jae Kwang Kim Sun-Hwa Ha Sun-Hyung Lim 《International journal of molecular sciences》2016,17(9)
Anthocyanins and proanthocyanidins, the major flavonoids in black and red rice grains, respectively, are mainly derived from 3′,4′-dihydroxylated leucocyanidin. 3′-Hydroxylation of flavonoids in rice is catalyzed by flavonoid 3′-hydroxylase (F3′H: EC 1.14.13.21). We isolated cDNA clones of the two rice F3′H genes (CYP75B3 and CYP75B4) from Korean varieties of white, black, and red rice. Sequence analysis revealed allelic variants of each gene containing one or two amino acid substitutions. Heterologous expression in yeast demonstrated that CYP75B3 preferred kaempferol to other substrates, and had a low preference for dihydrokaempferol. CYP75B4 exhibited a higher preference for apigenin than for other substrates. CYP75B3 from black rice showed an approximately two-fold increase in catalytic efficiencies for naringenin and dihydrokaempferol compared to CYP75B3s from white and red rice. The F3′H activity of CYP75B3 was much higher than that of CYP75B4. Gene expression analysis showed that CYP75B3, CYP75B4, and most other flavonoid pathway genes were predominantly expressed in the developing seeds of black rice, but not in those of white and red rice, which is consistent with the pigmentation patterns of the seeds. The expression levels of CYP75B4 were relatively higher than those of CYP75B3 in the developing seeds, leaves, and roots of white rice. 相似文献
16.
In this paper we present further evidence for the close control of fatty acid synthetase and stearoyl-CoA desaturase. Furthermore, we have established that whereas dietary palmitic acid may influence the activity of this desaturase but not of fatty acid synthetase, dietary linoleic acid appears to control both these enzymes. Finally, we have studied the influence of dietary fat and carbohydrate on the activities of the delta6 and delta5 desaturases. The former is only slightly affected by these dietary components. The delta5 desaturase activity is stimulated as the dietary fat content rises but is unaffected by dietary carbohydrate. The control of these enzymes is therefore independent of the control of fatty acid synthetase and stearoyl-CoA desaturase. From the data presented, the magnitude of the controlling effect of polyunsaturated fatty acids on fatty acid synthetase and stearoyl-CoA desaturase activity is determined and its relevance to lipogenesis in man based on daily intake of carbohydrate and linoleic acid is discussed. 相似文献
17.
P. K. Stumpf 《European Journal of Lipid Science and Technology》1984,86(9):361-363
In recent years, the precise localization of the plant acid synthesizing systems (EAS) in leaf and seed tissues has been elucidated. The molecular properties of plant FAS systems has also been determined in a number of laboratories. In particular the FAS systems of developing safflower seeds and spinach leaf tissue have been carefully examined. The results show clearly that unlike the FAS system in yeast cells and animal tissues, the plant systems are non-associated and very similar to those described for Escherichia coli. In addition, recent evidence has shown that β-ketoacyl-ACP synthetase I is involved with the other enzymes of the FAS system to form palmitic acid whereas β-ketoacyl-ACP synthetase II with the other enzymes of the FAS system controls the conversion of palmitic to stearic acid. An overall, generalized scheme will be presented to summarize the current views concerning plant fatty acid synthesis. 相似文献
18.
We have studied the effect of streptozotocin (SZ)-induced diabetes on fatty acyltransferase and phospholipase enzyme activities
involved in the synthesis and degradation of rat liver phosphoglycerides. Neither mitochondrial nor microsomal acyl-CoA: glycerol
3-phosphate acyltransferase (GPAT) activity was altered, although insulin treatment stimulated mitochondrial GPAT activity.
However, microsomal acyl-CoA: 1-acylglycerol 3-phosphate acyltransferase (1-acyl-GPAT) activity increased (24–33 per cent,
p<0.01) in the diabetic animals using 3 different acyl-CoA donors: palmitoyl-CoA, oleoyl-CoA and linoleoyl-CoA. SZ-induced
diabetes also increased acyl-CoA:1-acylglycerol 3-phosphorylcholine acyltransferase (GPCAT) activity (38–45 per cent, p<0.01)
with 3 different acyl-CoA donors: oleoyl-CoA, linoleoyl-CoA and arachidonoyl-CoA. 1-acyl-GPAT and GPCAT activity returned
to normal with insulin treatment. In contrast to the increased activity of the microsomal fatty acyltransferases 1-acyl-GPAT
and GPCAT, SZ-induced diabetes decreased mitochondrial phospholipase A2 activity and lysophospholipase activity (49–70 per cent, p<0.01). Insulin treatment of the diabetic rats corrected the decreased
lysophospholipase and stimulated phospholipase A2 activity 35 per cent higher than controls. Since microsomal 1-acyl-GPAT and GPCAT are known to have higher activity toward
unsaturated fatty acyl-CoA donors, the increased GPCAT activity coupled with the decreased lysophospholipase activity and
the increased 1-acyl-GPAT activity in diabetes would tend to increase the formation of newly synthesized phospholipids containing
unsaturated fatty acids. This mechanism plus the decreased fatty acid desaturase (4) may be the factors which alter the fatty
acid composition of phosphoglycerides in diabetic rat liver microsomes. 相似文献
19.
Estrogen administered to one-month-old female chickens resulted in a 180-fold increase in the amount of fatty acid synthetase,
a seven-fold increase in the enzyme activity per gram of tissue and a 25-fold increase in the weight of the oviduct. In contrast,
the fatty acid synthetase content in liver increased three-fold; activity per gram of tissue increased two-fold and the weight
increased two-fold. The alrge increase in the fatty acid synthetase activity in the oviduct was due to a corresponding increase
in the amount of the fatty acid synthetase protein since the specific activities of highly purified preparations of oviduct
and liver fatty acid synthetases were the same and the two enzymes had the same end point as determined by immunoprecipitation.
That the increase in activity of the oviduct enzyme is not due to a modification was further supported by physicochemical
comparison of the oviduct enzyme with the chicken liver enzyme. Thus, the synthetase complexes have similar size, their subunit
composition and size appear to be the same, and both are multifunctional enzymes. Finally, kinetic studies and product analyses
indicated no catalytic difference between the enzyme induced by estrogen in the oviduct and the liver enzyme. 相似文献
20.
Microsomes of developing soya bean cotyledons transfer oleate from oleoyl-CoA to phosphatidylcholine (PC) by two different
mechanisms: one in which oleate transfer is accompanied by the release of free CoA and another which results in the exchange
of oleate from oleoyl-CoA for unsaturated 18-carbon fatty acids of PC. The acyl exchange can be demonstrated only when bovine
serum albumin is present in the incubation medium. ATP-dependent acyl-CoA synthetase is not involved in the exchange process,
which apparently does not require any cofactors. In light of this exchange process, the oleate desaturase system was reinvestigated
in order to determine what the actual substrate for this system is. Upon incubation of microsomes with high concentrations
of [14C] oleoyl-CoA, bovine serum albumin and NADH, it could be conclusively demonstrated that most oleic acid is desaturated while
part of the PC molecule. The amounts of [14C] linoleoyl-CoA formed could be explained entirely by the acyl exchange. The physiological significance of the acyl exchange
system is discussed. A new method for separation of acyl-CoA from other lipids and free CoA using reversed phase column chromatography
also is described. 相似文献