Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mathematical model is proposed to describe the interaction between glycolysis, the Krebs cycle and 3-oxidation (beta OX). The model incorporates the activations of phosphofructokinase by AMP and of isocitrate dehydrogenase by ADP as well as the inhibitions of citrate synthase by citrate, of acyl CoA synthase by excess CoAsAcyl, of pyruvate dehydrogenase (PDH) and the beta OX helix by the products CoAsAc and NADH. These regulations have been shown to provide consecutive triggering of the fatty acid and glucose oxidation systems with an increase in the ATPase load, the beta OX of fatty acids being a major source of energy at small loads. The steady state rates of glycolysis and PDH-reaction begin to increase at larger loads when the rate of beta OX is close to its maximum value. At maximum ATPase loads, the glucose oxidation accounts for more than 80% of the total energy production. Under limited fatty acid supply, the transfer to glucose oxidation gives rise to a region of the ATPase loads, where in the steady state levels of NADH and CoAsAc increase with load.
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PMID:[Ratio between carbohydrate and lipid metabolism in muscle cell energy metabolism during ATPase loading. Mathematical model]. 645 74

We examined the effects of 8 wk of intense endurance training on free fatty acid (FFA) transporters and metabolism in resting and contracting soleus muscle using pulse-chase procedures. Endurance training increased maximal citrate synthase activity in red muscles (+54 to +91%; P </= 0.05) but failed to increase cytosolic fatty acid binding protein content, mRNA for fatty acyl-CoA synthase, and the putative FFA transporters or transport of palmitic acid into giant sarcolemmal vesicles. At rest, only triacylglycerol (TG) synthesis was significantly increased by training (+100.9 +/- 8.7 vs. +66.6 +/- 6.7 nmol/g wet wt; P </= 0.05). Muscle contraction increased TG synthesis (+46%; P </= 0.05) and palmitate oxidation (+115%; P </= 0.05) in untrained rats. Endurance training further enhanced synthesis of monoacylglycerol (MG), diacylglycerol (DG) and TG during contraction (+36, +69 and +71%, respectively; P </= 0.05), as well as exogenous palmitate oxidation (+41%; P </= 0.05) relative to untrained rats. Compared with those in untrained rats, TG breakdown and oxidation during contraction were reduced after training by 49 and 30%, respectively (P </= 0.05). In conclusion, endurance training 1) increases FFA oxidation and incorporation into endogenous lipid pools during contraction and 2) reduces the rate of intramuscular TG utilization during contraction when exogenous FFA availability is adequate. The enhanced FFA uptake subsequent to training appears to be independent of altered maximal transport rates of FFA into the muscle cell.
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PMID:Endurance training increases FFA oxidation and reduces triacylglycerol utilization in contracting rat soleus. 1078 Sep 32

Enzymic activities and gene expression of oleoyl-CoA elongase were studied during seed development using two different rapeseed cultivars, high-erucic-acid rapeseed (HEAR) and low-erucic-acid rapeseed (LEAR). The overall elongase activities were maximal in HEAR between the fourth and eighth weeks after pollination (WAP) and absent in LEAR. The 3-ketoacyl-CoA synthase (condensing enzyme, CE) mRNA levels and the developmental profiles in the two cultivars were different since maximal expression levels were detected in HEAR and LEAR at WAP 4 and WAP 6, respectively. Anti-CE antibodies revealed two proteins of 60 and 67 kDa in both cultivars and an additional reacting protein of 57 kDa in HEAR.
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PMID:Enzymic activities and gene expression of enzymes of the acyl-CoA elongase during rapeseed development. 1117 Nov 55

The fatty acid elongase-1 beta-ketoacyl-CoA synthase, FAE1 KCS, a seed-specific elongase condensing enzyme from Arabidopsis, is involved in the production of eicosenoic (C20:1) and erucic (C22:1) acids. Alignment of the amino acid sequences of FAE1 KCS, KCS1, and five other putative elongase condensing enzymes (KCSs) revealed the presence of six conserved cysteine and four conserved histidine residues. Each of the conserved cysteine and histidine residues was individually converted by site-directed mutagenesis to both alanine and serine, and alanine and lysine respectively. After expression in yeast cells, the mutant enzymes were analyzed for their fatty acid elongase activity. Our results indicated that only cysteine 223 is an essential residue for enzyme activity, presumably for acyl chain transfer. All histidine substitutions resulted in complete loss of elongase activity. The loss of activity of these mutants was not due to their lower expression level since immunoblot analysis confirmed each was expressed to the same extent as the wild type FAE1 KCS.
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PMID:Active-site residues of a plant membrane-bound fatty acid elongase beta-ketoacyl-CoA synthase, FAE1 KCS. 1134 60

Plant fatty acid elongase which catalyzes very-long-chain fatty acid (VLCFA) biosynthesis is a membrane-bound multienzyme complex. It is composed of four enzymes, a 3-ketoacyl-CoA synthase (condensing enzyme), a 3-ketoacyl-CoA reductase, a 3-hydroxyacyl-CoA dehydrase, and an enoyl-CoA reductase required for completion of each step of 2-carbon elongation of fatty acids. To improve our understanding of the overall regulation of the fatty acid elongase, we investigated the spatial and temporal expression of its key component, the FAE1-condensing enzyme, and examined the activity of the promoter of the FAE1 gene in Arabidopsis. In situ hybridization results revealed that FAE1 transcripts were found exclusively in the embryo. RNA blot analysis and histochemical analysis of GUS activity in pFAE1::GUS transgenic Arabidopsis lines demonstrated that the FAE1 gene was already transcribed in the early torpedo stage embryos 4-5 days after flowering, with transcription reaching its peak 9-11 days after flowering. VLCFA deposition closely paralleled FAE1 transcript accumulation. FAE1 promoter was highly active and embryo-specific. Because its timing coincides with the period of major storage lipid accumulation, and because its in vivo activity in Arabidopsis is superior to the napin promoter, FAE1 promoter may be ideal for genetic engineering of seed oil composition.
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PMID:Expression of the FAE1 gene and FAE1 promoter activity in developing seeds of Arabidopsis thaliana. 1157 26

The Arabidopsis FAE1 beta-ketoacyl-CoA synthase (FAE1 KCS) catalyzes the condensation of malonyl-CoA with long-chain acyl-CoAs. Sequence analysis of FAE1 KCS predicted that this condensing enzyme is anchored to a membrane by two adjacent N-terminal membrane-spanning domains. In order to characterize the FAE1 KCS and analyze its mechanism, FAE1 KCS and its mutants were engineered with a His6-tag at their N-terminus, and expressed in Saccharomyces cerevisiae. The membrane-bound enzyme was then solubilized and purified to near homogeneity on a metal affinity column. Wild-type recombinant FAE1 KCS was active with several acyl-CoA substrates, with highest activity towards saturated and monounsaturated C16 and C18. In the absence of an acyl-CoA substrate, FAE1 KCS was unable to carry out decarboxylation of [3-(14)C]malonyl-CoA, indicating that it requires binding of the acyl-CoA for decarboxylation activity. Site-directed mutagenesis was carried out on the FAE1 KCS to assess if this condensing enzyme was mechanistically related to the well characterized soluble condensing enzymes of fatty acid and flavonoid syntheses. A C223A mutant enzyme lacking the acylation site was unable to carry out decarboxylation of malonyl-CoA even when 18:1-CoA was present. Mutational analyses of the conserved Asn424 and His391 residues indicated the importance of these residues for FAE1-KCS activity. The results presented here provide the initial analysis of the reaction mechanism for a membrane-bound condensing enzyme from any source and provide evidence for a mechanism similar to the soluble condensing enzymes.
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PMID:Engineering and mechanistic studies of the Arabidopsis FAE1 beta-ketoacyl-CoA synthase, FAE1 KCS. 1213 93

We examined the effects of undernutrition on muscle development during the first postnatal week in pigs. Eighteen piglets were subjected to three nutritional levels (300, 200 or 100 g/(kg body. d) of colostrum then milk) between birth and slaughter at 7 d of age. Longissimus lumborum (LL), a fast-twitch glycolytic muscle, and rhomboideus (RH), a mixed slow- and fast-twitch oxido-glycolytic muscle, were taken for myofiber typing and biochemical analyses. Enzyme activities of lactate dehydrogenase (LDH), citrate synthase (CS) and beta-hydroxy-acyl-CoA-dehydrogenase (HAD) were used as markers of glycolytic, oxidative and lipid beta-oxidation capacities, respectively. Undernutrition selectively decreased (P < 0.001) hypertrophy of the future fast-twitch glycolytic fibers in LL. Contractile and metabolic maturation was delayed in the later maturing LL, as reflected by a decrease in muscle protein concentration (P < 0.01), an increase (P < 0.05) in the percentage of myofibers still expressing the fetal myosin heavy chain (MyHC), a lower postnatal increase in LDH activity (P < 0.001) and a delayed decrease in the percentage of IIa MyHC positive fibers (P < 0.001). Otherwise, restriction tended (P < 0.10) to increase the percentage of slow type I MyHC containing fibers in both muscles and of alpha-cardiac MyHC positive fibers in RH (P < 0.05). The LDH/CS ratio decreased dramatically (P < 0.001) after restriction, to a greater extent in LL than in RH. These changes denoted a more oxidative metabolism using fewer carbohydrates and more lipids in restricted pigs, as suggested by the increased activity of HAD (P < 0.001) and decreased respiratory quotient (P < 0.001).
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PMID:Early postnatal food intake alters myofiber maturation in pig skeletal muscle. 1251 81

The fatty acid elongase [often designated FAE or beta-(or 3-) ketoacyl-CoA synthase] is a condensing enzyme and is the first component of the elongation complex involved in synthesis of erucic acid (22:1) in seeds of garden nasturtium (Tropaeolum majus). Using a degenerate primers approach, a cDNA of a putative embryo FAE was obtained showing high homology to known plant elongases. This cDNA contains a 1,512-bp open reading frame that encodes a protein of 504 amino acids. A genomic clone of the nasturtium FAE was isolated and sequence analyses indicated the absence of introns. Northern hybridization showed the expression of this nasturtium FAE gene to be restricted to the embryo. Southern hybridization revealed the nasturtium beta-ketoacyl-CoA synthase to be encoded by a small multigene family. To establish the function of the elongase homolog, the cDNA was introduced into two different heterologous chromosomal backgrounds (Arabidopsis and tobacco [Nicotiana tabacum]) under the control of a seed-specific (napin) promoter and the tandem 35S promoter, respectively. Seed-specific expression resulted in up to an 8-fold increase in erucic acid proportions in Arabidopsis seed oil, while constitutive expression in transgenic tobacco tissue resulted in increased proportions of very long chain saturated fatty acids. These results indicate that the nasturtium FAE gene encodes a condensing enzyme involved in the biosynthesis of very long chain fatty acids, utilizing monounsaturated and saturated acyl substrates. Given its strong and unique preference for elongating 20:1-CoA, the utility of the FAE gene product for directing or engineering increased synthesis of erucic acid is discussed.
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PMID:Seed-specific heterologous expression of a nasturtium FAE gene in Arabidopsis results in a dramatic increase in the proportion of erucic acid. 1533 57

The optimal utilization of energy substrates in muscle fibers is of primary importance for muscle contraction and whole body physiology. This study aimed to investigate the age-related changes in some indicators of glucose catabolism and fatty acid oxidation in muscles of growing rabbits. Longissimus lumborum (fast-twitch, LL) and semimembranosus proprius (slow-twitch, SMP) muscles were collected at 10 or 20 weeks of age ( n=6 per age). Glucose transporter GLUT4 content was investigated by immunoblot assay. Activity levels of five enzymes were measured: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS), isocitrate dehydrogenase (ICDH) and -3-hydroxyacyl-coenzyme A dehydrogenase (HAD) for oxidation. Mitochondrial and peroxisomal oxidation rates were assessed on fresh homogenates using [1-14C]-oleate as substrate. At both ages, mitochondrial and peroxisomal oxidations rates, as well as activities of oxidative enzymes were higher in SMP than in LL. In both muscles, the apparent rate of fatty acid oxidation by the mitochondria did not differ between the two ages. However, a decrease in the activities of the three oxidative enzymes was observed in LL, whereas activities of CS and HAD and peroxisomal oxidation rate of oleate increased between the two ages in SMP muscle. In both muscles, LDH activity increased between 10 and 20 weeks, without variations in glucose uptake (GLUT4 transporter content) and in the first step of glucose utilization (PFK activity). In conclusion, mitochondrial oxidation rate of fatty acids and activities of selected mitochondrial enzymes were largely unrelated. Moreover, regulation of energy metabolism with advancing age differed between muscle types.
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PMID:Age-related changes in glucose utilization and fatty acid oxidation in a muscle-specific manner during rabbit growth. 1554 70

The marine parasitic protozoon Perkinus marinus synthesizes the polyunsaturated fatty acid arachidonic acid via the unusual alternative Delta8 pathway in which elongation of C18 fatty acids generates substrate for two sequential desaturations. Here we have shown that genes encoding the three P. marinus activities responsible for arachidonic acid biosynthesis (C18 Delta9-elongating activity, C20 Delta8 desaturase, C20 Delta5 desaturase) are genomically clustered and co-transcribed as an operon. The acyl elongation reaction, which underpins this pathway, is catalyzed by a FAE1 (fatty acid elongation 1)-like 3-ketoacyl-CoA synthase class of condensing enzyme previously only reported in higher plants and algae. This is the first example of an elongating activity involved in the biosynthesis of a polyunsaturated fatty acid that is not a member of the ELO/SUR4 family. The P. marinus FAE1-like elongating activity is sensitive to the herbicide flufenacet, similar to some higher plant 3-ketoacyl-CoA synthases, but unable to rescue the yeast elo2Delta/elo3Delta mutant consistent with a role in the elongation of polyunsaturated fatty acids. P. marinus represents a key organism in the taxonomic separation of the single-celled eukaryotes collectively known as the alveolates, and our data imply a lineage in which ancestral acquisition of plant-like genes, such as FAE1-like 3-ketoacyl-CoA synthases, occurred via endosymbiosis. The P. marinus FAE1-like elongating activity is also indicative of the independent evolution of the alternative Delta8 pathway, distinct from ELO/SUR4-dependent examples.
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PMID:Co-transcribed genes for long chain polyunsaturated fatty acid biosynthesis in the protozoon Perkinsus marinus include a plant-like FAE1 3-ketoacyl coenzyme A synthase. 1709 43


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