| 1. |
- Abou-Hachem, Maher, et al.
(författare)
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Calcium binding and thermostability of carbohydrate binding module CBM4-2 of Xyn10A from Rhodothermus marinus.
- 2002
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 41:18, s. 5720-5729
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Tidskriftsartikel (refereegranskat)abstract
- Calcium binding to carbohydrate binding module CBM4-2 of xylanase 10A (Xyn10A) from Rhodothermus marinus was explored using calorimetry, NMR, fluorescence, and absorbance spectroscopy. CBM4-2 binds two calcium ions, one with moderate affinity and one with extremely high affinity. The moderate-affinity site has an association constant of (1.3 +/- 0.3) x 10(5) M(-1) and a binding enthalpy DeltaH(a) of -9.3 +/- 0.4 kJ x mol(-1), while the high-affinity site has an association constant of approximately 10(10) M(-1) and a binding enthalpy DeltaH(a) of -40.5 +/- 0.5 kJ x mol(-1). The locations of the binding sites have been identified by NMR and structural homology, and were verified by site-directed mutagenesis. The high-affinity site consists of the side chains of E11 and D160 and backbone carbonyls of E52 and K55, while the moderate-affinity site comprises the side chain of D29 and backbone carbonyls of L21, A22, V25, and W28. The high-affinity site is in a position analogous to the calcium site in CBM4 structures and in a recent CBM22 structure. Binding of calcium increases the unfolding temperature of the protein (T(m)) by approximately 23 degrees C at pH 7.5. No correlation between binding affinity and T(m) change was noted, as each of the two calcium ions contributes almost equally to the increase in unfolding temperature.
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| 2. |
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| 3. |
- Büchert, A., et al.
(författare)
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Dioxin contamination in food : Bayreuth, Germany, from September 28 to October 1, 2000
- 2001
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Ingår i: Environmental Science and Pollution Research. - : Ecomed Publishers. - 0944-1344 .- 1614-7499. ; 8:2, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Dioxin and PCB monitoring programs for food and feeding stuff in most countries of the world, including many European Countries are currently inadequate. Better control of food production lines and food processing procedures is needed to minimize entry of dioxin to the food chain and will help to avoid dioxin contamination accidents. This would also improve the ability to trace back a possible contamination to its source. European guidelines for monitoring programs should be established to ensure comparable and meaningful results. These guidelines should define the minimum requirements for the design of monitoring programs, analytical methods, and quality assurance.Though data from Northern Europe shows that the general population exposure to dioxin and PCB has decreased during the last ten years these compounds continue to be a risk of accidental contamination of the food chain. The most prominent recent example is the Belgian dioxin contamination of feeding stuff in 1999. The Belgian dioxin contamination was not detected due to dioxin monitoring programs but by their direct biological effects seen in animals. Four other cases of dioxin contamination have been detected in Europe since 1997 due to local monitoring programs. One of them (citrus pulp pellets 1998) was in a much larger scale than the Belgian dioxin contamination.The general population's exposure to dioxins and PCBs is still in the same range (1-4 pg WHO-TEQ/kg body weight and day) as the recently revised WHO tolerable daily intake (TDI). There is concern that short-term high level exposure to dioxins, furans, and PCB may cause biological effects on the human fetal development and further research is required.Further actions to control sources building on considerable advances already made in many countries may need to be supplemented by measures to prevent direct contamination of feeding stuff or food to reduce general population exposure further.
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| 4. |
- Carroll, L. J., et al.
(författare)
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Prognosis for mild traumatic brain injury : Results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury
- 2004
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 43, s. 61-
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Forskningsöversikt (refereegranskat)abstract
- We searched the literature on the epidemiology, diagnosis, prognosis, treatment and costs of mild traumatic brain injury. Of 428 studies related to prognosis after mild traumatic brain injury, 120 (28%) were accepted after critical review. These comprise our best-evidence synthesis on prognosis after mild traumatic brain injury. There was consistent and methodologically sound evidence that children's prognosis after mild traumatic brain injury is good, with quick resolution of symptoms and little evidence of residual cognitive, behavioural or academic deficits. For adults, cognitive deficits and symptoms are common in the acute stage, and the majority of studies report recovery for most within 3-12 months. Where symptoms persist, compensation/litigation is a factor, but there is little consistent evidence for other predictors. The literature on this area is of varying quality and causal inferences are often mistakenly drawn from cross-sectional studies.
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| 5. |
- Caye-Thomasen, P, et al.
(författare)
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Depletion of mucosal substance P in acute otitis media
- 2004
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 794-797
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Tidskriftsartikel (refereegranskat)abstract
- Objective-The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve fiber release of SP. Material and Methods-To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was measured using a radioimmunoassay. Results-Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. Conclusion-SP seems to be depleted in the rat middle ear mucosa in the hyperacute phase of AOM. This depletion is followed by replenishment and the concentration of SP approaches its normal level 6 days post-inoculation. The release of SP may be the trigger of the concurrent bone resorption and may further augment the inflammatory response to the bacterial colonization.
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| 6. |
- Rask, Eva, 1958-, et al.
(författare)
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Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men
- 2001
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:9, s. 1640-1645
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.RESEARCH DESIGN AND METHODS:From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.RESULTS:Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses.CONCLUSIONS:In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.
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| 7. |
- Abou Hachem, Maher, et al.
(författare)
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Carbohydrate-binding modules from a thermostable Rhodothermus marinus xylanase : Cloning, expression and binding studies
- 2000
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Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021. ; 345:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- The two N-terminally repeated carbohydrate-binding modules (CBM4-1 and CBM4-2) encoded by xyn10A from Rhodothermus marinus were produced in Escherichia coli and purified by affinity chromatography. Binding assays to insoluble polysaccharides showed binding to insoluble xylan and to phosphoric-acid-swollen cellulose but not to Avicel or crystalline cellulose. Binding to insoluble substrates was significantly enhanced by the presence of Na+ and Ca2+ ions. The binding affinities for soluble polysaccharides were tested by affinity electrophoresis; strong binding occurred with different xylans and β-glucan. CBM4-2 displayed a somewhat higher binding affinity than CBM4-1 for both soluble and insoluble substrates but both had similar specificities. Binding to short oligosaccharides was measured by NMR; both modules bound with similar affinities. The binding of the modules was shown to be dominated by enthalpic forces. The binding modules did not contribute with any significant synergistic effects on xylan hydrolysis when incubated with a Xyn10A catalytic module. This is the first report of family 4 CBMs with affinity for both insoluble xylan and amorphous cellulose.
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| 8. |
- Abou-Hachem, Maher, et al.
(författare)
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The modular organisation and stability of a thermostable family 10 xylanase
- 2003
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Ingår i: Biocatalysis and Biotransformation. - : Informa UK Limited. - 1024-2422 .- 1029-2446. ; 21:5-6, s. 253-260
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Tidskriftsartikel (refereegranskat)abstract
- The thermophilic marine bacterium Rhodothermus marinus produces a modular family 10 xylanase (Xyn10A). It consists of two N-terminal family 4 carbohydrate binding modules (CBMs) followed by a domain of unknown function (D3), and a catalytic module (CM) flanked by a small fifth domain (D5) at its C-terminus. Several truncated mutants of the enzyme have been produced and characterised with respect to biochemical properties and stability. Multiple calcium binding sites are shown to be present in the two N-terminal CBMs and recent evidence suggests that the third domain of the enzyme also has the ability to bind the same metal ligand. The specific binding of Ca2+ was demonstrated to have a pronounced effect on thermostability as shown by differential scanning calorimetry and thermal inactivation studies. Furthermore, deletion mutants of the enzyme were less stable than the full-length enzyme suggesting that module interactions contributed to the stability of the enzyme. Finally, recent evidence indicates that the fifth domain of Xyn10A is a novel type of module mediating cell-attachment.
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| 10. |
- Kvist Reimer, Martina, et al.
(författare)
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Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice.
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 146:5, s. 717-727
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Inhibitors of the glucagon-like peptide-1 (GLP-1)-degrading enzyme, dipeptidyl peptidase IV (DPPIV), are being explored in the treatment of diabetes. We examined the long-term influence of a selective, orally active inhibitor of DPPIV (NVP DPP728), in normal female C57BL/6J mice and such mice rendered glucose-intolerant and insulin-resistant by feeding a high-fat diet. DESIGN: In mice fed a standard diet (11% fat) or a high-fat diet (58% fat), NVP DPP728 (0.12 micromol/g body weight) was administered in the drinking water for an 8 week period. RESULTS: DPPIV inhibition reduced plasma DPPIV activity to 0.01+/-0.03 mU/ml vs 3.26+/-0.19 mU/ml in controls (P<0.001). Glucose tolerance after gastric glucose gavage, as judged by the area under the curve for plasma glucose levels over the 120 min study period, was increased after 8 weeks by NVP DPP728 in mice fed normal diet (P=0.029) and in mice fed a high-fat diet (P=0.036). This was accompanied by increased plasma levels of insulin and intact GLP-1. Glucose-stimulated insulin secretion from islets isolated from NVP DPP728-treated animals after 8 weeks of treatment was increased as compared with islets from control animals at 5.6, 8.3 and 11.1 mmol/l glucose both in mice fed normal diet and in mice fed a high-fat diet (both P<0.05). Islet insulin and glucagon immunocytochemistry revealed that NVP DPP728 did not affect the islet architecture. However, the expression of immunoreactive glucose transporter isoform-2 (GLUT-2) was increased by DPPIV inhibition, and in mice fed a high-fat diet, islet size was reduced after treatment with NVP DPP728 from 16.7+/-2.6 x 10(3) microm(2) in controls to 7.6+/-1.0 x 10(3) microm(2) (P=0.0019). CONCLUSION: Long-term DPPIV inhibition improves glucose tolerance in both normal and glucose-intolerant mice through improved islet function as judged by increased GLUT-2 expression, increased insulin secretion and protection from increased islet size in insulin resistance.
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| 11. |
- Peloso, Paul M, et al.
(författare)
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Critical evaluation of the existing guidelines on mild traumatic brain injury.
- 2004
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 43, s. 106-
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of guidelines is to reduce practice variability, but they need to be evidence-based. We examine current mild traumatic brain injury guidelines, critique their basis in evidence and examine their variability in recommendations. A systematic search of the literature found 38,806 abstracts, with 41 guidelines. There were 18 sports-related guidelines, 13 related to admission policies, 12 related to imaging and 5 related to neuropsychological assessment. Some guidelines addressed several areas. Only 5 guidelines reported a methodology for the assembly of evidence used to develop the guideline. After appraising the guidelines against a validated index, we found that 3 of the 41 guidelines could be categorized as evidence-based. Two of these focused on paediatric patients and 1 on adult patients. Limited methodological quality in the current guidelines results in conflicting recommendations amongst them.
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| 12. |
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| 13. |
- Ahrén, Bo, et al.
(författare)
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Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans.
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:10, s. 2860-2864
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI. CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.
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| 23. |
- Nilsson, Mikael, et al.
(författare)
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Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins1,2,3
- 2004
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 80:5, s. 1246-1253
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Tidskriftsartikel (refereegranskat)abstract
- Background: Milk products deviate from other carbohydrate-containing foods in that they produce high insulin responses, despite their low GI. The insulinotropic mechanism of milk has not been elucidated. Objective: The objective was to evaluate the effect of common dietary sources of animal or vegetable proteins on concentrations of postprandial blood glucose, insulin, amino acids, and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1] in healthy subjects. Design: Twelve healthy volunteers were served test meals consisting of reconstituted milk, cheese, whey, cod, and wheat gluten with equivalent amounts of lactose. An equicarbohydrate load of white-wheat bread was used as a reference meal. Results: A correlation was found between postprandial insulin responses and early increments in plasma amino acids; the strongest correlations were seen for leucine, valine, lysine, and isoleucine. A correlation was also obtained between responses of insulin and GIP concentrations. Reconstituted milk powder and whey had substantially lower postprandial glucose areas under the curve (AUCs) than did the bread reference (–62% and –57%, respectively). Whey meal was accompanied by higher AUCs for insulin (90%) and GIP (54%). Conclusions: It can be concluded that food proteins differ in their capacity to stimulate insulin release, possibly by differently affecting the early release of incretin hormones and insulinotropic amino acids. Milk proteins have insulinotropic properties; the whey fraction contains the predominating insulin secretagogue.
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| 24. |
- Nilsson, O, et al.
(författare)
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Localization of estrogen receptors-alpha and -beta and androgen receptor in the human growth plate at different pubertal stages
- 2003
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 177:2, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- Sex steroids are required for a normal pubertal growth spurt and fusion of the human epiphyseal growth plate. However, the localization of sex steroid receptors in the human pubertal growth plate remains controversial. We have investigated the expression of estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR) in biopsies of proximal tibial growth plates obtained during epiphyseal surgery in 16 boys and eight girls. All pubertal stages were represented (Tanner stages 1-5). ERalpha, ERbeta and AR were visualized with immunohistochemistry and the number of receptor-positive cells was counted using an image analysis system. Percent receptor-positive chondrocytes were assessed in the resting, proliferative and hypertrophic zones and evaluated for sex differences and pubertal trends. Both ERalpha- and ERbeta-positive cells were detected at a greater frequency in the resting and proliferative zones than in the hypertrophic zone (64+/-2%, 64+/-2% compared with 38+/-3% for ERalpha, and 63+/-3%, 66+/-3% compared with 53+/-3% for ERbeta), whereas AR was more abundant in the resting (65+/-3%) and hypertrophic zones (58+/-3%) than in the proliferative zone (41+/-3%). No sex difference in the patterns of expression was detected. For ERalpha and AR, the percentage of receptor-positive cells was similar at all Tanner pubertal stages, whereas ERbeta showed a slight decrease in the proliferative zone during pubertal development (P<0.05). In summary, our findings suggest that ERalpha, ERbeta and AR are expressed in the human growth plate throughout pubertal development, with no difference between the sexes.
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| 25. |
- Nordberg Karlsson, Eva, et al.
(författare)
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Rhodothermus marinus: a thermophilic bacterium producing dimeric and hexameric citrate synthase isoenzymes.
- 2002
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Ingår i: Extremophiles. - : Springer Science and Business Media LLC. - 1433-4909 .- 1431-0651. ; 6:1, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- Two separate citrate synthases from the extremely thermophilic bacterium Rhodothermus marinus have been identified and purified. One of the enzymes is a hexameric protein and is the first thermostable, hexameric citrate synthase to be isolated. The other is a dimeric enzyme, which is also thermostable but possesses both citrate synthase and 2-methyl citrate synthase activities. 2-Methyl citrate synthase uses propionyl-coenzyme A as one of its substrates and in Escherichia coli, for example, it has been implicated in the metabolism of propionate. However, no growth of R. marinus was observed using minimal medium with propionate as the sole carbon source, and both hexameric and dimeric enzymes were produced irrespective of whether propionate was included in the growth medium. The data are discussed with respect to the evolutionary relationships between the known hexameric and dimeric citrate synthases and 2-methyl citrate synthase.
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