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PubMed1988

Evidence of increased association of fibrinogen with platelets caused by sodium citrate.

Washed platelet suspensions are almost always prepared from blood anticoagulated with sodium citrate. Because citrate has been reported to affect platelet function, we examined the involvement of citrate on the platelet-fibrinogen interactions. More iodine 125-labeled fibrinogen was bound on washed platelets from citrate-anticoagulated blood (CP) than on washed platelets from non-anticoagulated blood (PNB) obtained by the rapid gel filtration of native blood from the same donor. Scatchard analyses of the equilibrium binding data gave linear plots for PNB indicating a single class of binding sites with 16,480 +/- 2,800 fibrinogen molecules bound per platelet (Kd 5.6 x 10(-7) mol/L); CP gave curvilinear plots that, when resolved into two components assuming two classes of binding sites, gave a high-affinity site (4,950 +/- 970 molecules per platelet; Kd 1.29 x 10(-7) mol/L) and a low-affinity site (25,660 +/- 4,600 molecules per platelet; Kd 1.02 x 10(-6) mol/L). When blood from one donor was collected into 10 mmol/L and 20 mmol/L citrate, increased binding of 125I-fibrinogen was observed on platelets exposed to 20 mmol/L citrate. Exposure of PNB to varying citrate concentrations showed enhanced fibrinogen binding with increasing citrate concentrations; differences in the Kd values between non-citrate-treated PNB and citrate-treated PNB were apparent at about 7.5 mmol/L of citrate. The effects of citrate in increasing the association of fibrinogen with platelets were not caused by variations in the pH; although fibrinogen binding was diminished at low pH of the citrate used, more binding was observed in the presence of citrate than with buffer of the same pH. The effects of citrate appear to be on the platelet fibrinogen receptor because nonspecific binding was not affected by the citrate. Inasmuch as no carbon 14-labeled citric acid binding to platelets was observed, citrate may affect the platelet-fibrinogen interactions without binding to the platelets. We conclude that platelet exposure to citrate increases the fibrinogen binding and may lead to the appearance of curved Scatchard plots.

Blood Platelets↗
PubMed1999

Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss.

The study was performed to ascertain the value of potassium magnesium citrate, magnesium citrate, and potassium citrate in overcoming thiazide-induced hypokalemia and magnesium loss. Sixty-two healthy subjects were first administered hydrochlorothiazide, 50 mg/d. After 3 weeks of thiazide treatment (or earlier for potassium level </=3.5 mEq/L), they were randomized to receive one of three drugs while continuing to receive thiazide: potassium magnesium citrate (49 mEq of potassium, 24.5 mEq of magnesium), magnesium citrate (24.5 mEq/d of magnesium), or potassium citrate (49 mEq/d of potassium). Outcome measures were changes in serum potassium and magnesium levels and urinary potassium, magnesium, pH, and citrate values. All three drugs increased serum potassium concentration compared with that resulting from thiazide alone. Potassium magnesium citrate increased serum potassium levels from 3.3 +/- 0.2 to 3.8 +/- 0.3 mEq/L (P < 0.001), potassium citrate increased serum potassium levels from 3.4 +/- 0.4 to 3.9 +/-0.3 mEq/L (P < 0.001), and magnesium citrate from 3.4 +/- 0.4 to 3.7 +/- 0.3 mEq/L (P < 0.001). Potassium magnesium citrate led to a significant increase in urinary magnesium levels by the third week of supplementation (from 120 +/- 34 to 149 +/- 58 mg/d; P < 0.01) and produced a small but significant increase in serum magnesium level. Magnesium citrate significantly increased 24-hour urinary magnesium after the first week of supplementation and maintained this increase throughout the study. Potassium magnesium citrate and potassium citrate, but not magnesium citrate, significantly increased urinary pH and citrate values. Potassium magnesium citrate not only corrects thiazide-induced hypokalemia, but also may avert magnesium loss while providing an alkali load.

Adult↗
PubMed1983

The properties of citrate transport in membrane vesicles from Bacillus subtilis.

The uptake system for citrate is induced in Bacillus subtilis W23 by growth in the presence of citrate and only membrane vesicles isolated from these cells show energy-dependent citrate uptake. Citrate transport in membrane vesicles is strictly dependent on the presence of divalent cations such as Mg2+, Mn2+, Zn2+, Ba2+, Be2+, Ca2+, Cu2+, Co2+ or Ni2+. The initial rate of citrate transport increases with the divalent cation concentration up to a maximum. The maximum initial rate of citrate uptake is reached with 2 mM Mg2+. The cations form stable chelates with citrate. The metal citrate complex is the transported solute. This is demonstrated for citrate uptake in the presence of Ca2+. Membrane vesicles from citrate-grown cells accumulate Ca2+ and citrate only if both solutes are present. Citrate and Ca2+ are accumulated in equimolar quantities. The uptake of Ca2+ but not of citrate is inhibited by Mg2+. Uptake of the metal-citrate complex is inhibited by the uncoupler carbonylcyanide p-trifluoromethoxyphenyl-hydrazone and in the presence of K+ ions by valinomycin and nigericin. The inhibitory effects correlate with the effects observed on the components of the proton-motive force, indicating that the proton-motive force is a driving force for metal-citrate transport. The number of protons (n) symported with the metal-citrate complex has been determined under different experimental conditions from the steady state levels of citrate accumulation, the electrical potential and pH gradient. This number varies from 1 at pH 4.7 to 2 at pH 8.0.

Bacillus subtilis↗
PubMed1986

Citrate transport in rabbit nephron.

Citrate is an important renal metabolic substrate and urinary inhibitor of calcium stone formation. Our purpose was to characterize citrate reabsorption in the rabbit nephron using isolated perfused tubules. Citrate reabsorption, measured by luminal disappearance of [14C]citrate, was found only in the proximal tubule, not in the cortical thick ascending limb or the cortical collecting tubule. In the proximal convoluted tubule, the collected fluid was also analyzed by thin-layer chromatography and by measurements of chemical citrate concentration using an ultramicroassay. Luminal disappearance of [14C]citrate was determined to accurately represent citrate reabsorption; no significant citrate secretion was found. The absolute magnitude of citrate reabsorption was approximately 3.4 pmol X mm-1 X min-1 using either 1 or 3 mM citrate in the perfusate. This rate of citrate reabsorption in the rabbit proximal tubule could account for all of renal citrate reabsorption but was severalfold lower than glucose reabsorption, which was studied for comparative purposes. In contrast, the magnitude of succinate transport (which probably occurs via the same transport system as citrate) was comparable with that of citrate. Citrate reabsorption was inhibited approximately 80% by 10(-5) M ouabain. This characterization of citrate transport in the intact proximal tubule should provide a useful model to study regulation of urinary citrate excretion.

Absorption↗
PubMed1983

Mechanisms of citrate transport and exchange in corn mitochondria.

Previous work (Birnberg, Jayroe, Hanson 1982 Plant Physiol 70: 511-516) demonstrated that corn mitochondria (Zea mays L.) can accumulate citrate by a malate- and phosphate-independent proton symporter. This uptake and symport of other ions were investigated. Passive swelling experiments indicated that corn mitochondria can accumulate several other anions by proton symport, but only isocitrate is taken up nearly as effectively as citrate. At the optimal pH (4.5), active uptake of carrier-free [(14)C]citrate in 50 micromolar mersalyl is inhibited by fourteen anions, but only the I(50) (the concentration of inhibitor required to reduce uptake of carrier-free [(14)C]citrate by 50%) values of citrate (0.08 millimolar) and d-and l-isocitrate (0.5 millimolar) are less than 4 millimolar. Isocitrate is a competitive inhibitor of citrate uptake and [(14)C]isocitrate is accumulated with a K(m) similar similar to its I(50). Valinomycin reduces net active citrate accumulation at pH 7.5, consistent with the relatively low V(max) for citrate uptake. At pH 4.5, mersalyl reduces the rate of citrate uptake without changing the affinity of the carrier for citrate. Thus, the corn mitochondria have a high-affinity, mersalyl-insensitive carrier selective for citrate that also transports isocitrate.The pH optimum for oxidation of both endogenous substrates and citrate is approximately pH 6.8, but citrate oxidation is low at all pH values and is poorly coupled to ATP synthesis. Under active conditions only, at pH 7.0, malate/citrate exchange occurs with 4 millimolar malate being sufficient to remove about half the matrix citrate. Therefore, in vivo both citrate uptake by proton symport and efflux by malate/citrate exchange should occur, with the net direction of citrate movement determined by the cytoplasmic pH, and citrate and malate concentrations; in most cases, net efflux is likely to be favored.

Journal Article↗
PubMed2004

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women.

PURPOSE: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. MATERIALS AND METHODS: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis. RESULTS: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus. CONCLUSIONS: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.

Aged↗
PubMed1992

Physicochemical action of potassium-magnesium citrate in nephrolithiasis.

Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Transport of citrate across the brush border and basolateral membrane of rat small intestine.

It was the aim of the present study to investigate the transport of tricarboxylates (citrate, tricarballylate) across the basolateral membrane (BLM) of the small intestine. Experiments were performed using BLM vesicles isolated from the jejunum of rats. For comparison, some experiments with brush border membrane (BBM) vesicles were also performed. Finally, transfer of citrate and tricarballylate across the intestinal wall was investigated using sacs of everted small intestine. Uptake of citrate by BBM vesicles occurs by a Na+ gradient-driven transport mechanism specific for tri- and dicarboxylates. The partially protonated forms of citrate seem to be much better transported than the completely dissociated form, since lowering the extravesicular pH from 7.8 to 5.6 resulted in a marked stimulation of Na(+)-dependent citrate uptake. In contrast to citrate uptake across the BBM, uptake of citrate across the BLM was neither influenced by Na+ nor by pH changes. Neither structurally related tri- and dicarboxylates (tricarballylate, succinate) nor other organic and inorganic anions (e.g. lactate, p-aminohippurate, sulfate, chloride, bicarbonate) significantly influenced citrate uptake by BLM vesicles under cis-conditions. Uptake of citrate as a function of the extravesicular substrate concentration was linear over a concentration range from 0.1 to 10 mmol/l. Thus, citrate uptake under these conditions seems to be Na(+)-independent and not to be mediated by a carrier. However, preloading the BLMV with citrate clearly trans-stimulated the uptake of citrate and tricarballylate, respectively. Furthermore, citrate significantly inhibited tricarballylate uptake into BLMV preloaded with citrate. These results indicate uptake of tricarboxylates across the BLM by an exchange mechanism. Using sacs of everted small intestine, no transfer of intact citrate against a concentration gradient occurred, but some evidence for metabolization of citrate within the intestinal wall was obtained. In contrast, the non-metabolizable tricarboxylate tricarballylate was significantly accumulated in the serosal compartment of everted intestinal sacs.

Animals↗
PubMed1992

Citrate transport in proximal cell line.

Citrate uptake into kidney proximal tubules occurs via an apical dicarboxylate transporter and a poorly characterized process in the basolateral membrane. We used OK cells, a cell line derived from opossum kidney, to study citrate transport in proximal tubule-like cells. Citrate uptake into cell monolayers was studied using [14C]citrate with [3H]mannitol as a volume marker. Citrate uptake into these cells was sodium dependent and saturable with increasing concentrations of citrate. In contrast to previous models, citrate transport was altered minimally by changes in pH from 6.2 to 7.0 and increased at pH 7.4 to 7.8. A variety of di- and tricarboxylates were tested for interaction with citrate transport. The dicarboxylates succinate, malate, and oxaloacetate at 1 mM concentration inhibited citrate uptake minimally (uptake at least 80% of control); one dicarboxylate, alpha-ketoglutarate, did inhibit citrate uptake significantly. In contrast, the tricarboxylates isocitrate and tricarballylate inhibited citrate uptake significantly, indicating probable competitive inhibition with the transport process. These characteristics are distinctly different from those of the apical membrane dicarboxylate transporter. 1,2,3-Benzenetricarboxylic acid, an inhibitor of the mitochondrial tricarboxylate transporter, did not alter citrate uptake. In conclusion, the OK proximal cell line exhibits a novel citrate transport process compared with the apical transport of citrate described in most proximal systems. This transport process probably involves the trivalent species of citrate in contrast to the usual predominant transport of divalent citrate. This transport process may represent a process similar to that in the basolateral membrane of the proximal tubule.

Animals↗
PubMed2002

Citrate clearance in children receiving continuous venovenous renal replacement therapy.

Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.

Algorithms↗
PubMed1992

Gastrointestinal citrate absorption in nephrolithiasis.

Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

Adult↗
PubMed1990

Acquisition of iron from citrate by Pseudomonas aeruginosa.

Transport of [14C]citrate, ferric [14C]citrate and [55Fe]ferric citrate into Pseudomonas aeruginosa grown in synthetic media containing citrate, succinate, or succinate and citrate as carbon and energy sources was measured. Cells grown in citrate-containing medium transported radiolabelled citrate and iron, whereas the succinate-grown cells transported iron but not citrate. Binding studies revealed that isolated outer and inner membranes of citrate-grown cells contain a citrate receptor, absent from membranes of succinate-grown cells. [55Fe]Ferric citrate bound to the isolated outer membranes of each cell type. The failure of citrate to compete with this binding suggests the presence of a ferric citrate receptor on the outer membranes of each cell type. Citrate induced the synthesis of two outer-membrane proteins of 41 and 19 kDa. A third protein of 17 kDa was more dominant in citrate-grown cells than in succinate-grown cells.

Bacterial Outer Membrane Proteins↗
PubMed1988

Effect of pH on citrate reabsorption in the proximal convoluted tubule.

Urinary citrate is an important endogenous inhibitor of calcium nephrolithiasis. Systemic acidosis increases renal citrate reabsorption (decreases urinary excretion) and hence is associated with nephrolithiasis; systemic alkali administration increases citrate excretion. We studied the mechanism by which acidosis and alkalosis alter citrate reabsorption in the proximal convoluted tubule, the predominant nephron segment reabsorbing citrate. Tubules were perfused in vitro and citrate reabsorption was measured by use of luminal [14C]citrate. Changes in solution pH were accomplished by changes in bicarbonate concentration with constant PCO2. Decreasing peritubular pH acutely from 7.4 to 7.2 caused an increase in citrate reabsorption. However, the change seen with an acid peritubular pH was abolished by additional buffering of the luminal solution. Increasing peritubular pH from 7.4 to 7.6 resulted in a fall in citrate reabsorption that was not significantly greater than a time-dependent fall in citrate reabsorption in this preparation. The effect of luminal pH on proximal citrate reabsorption was also examined directly. Decreasing perfusate (luminal) pH from 7.4 to 7.2 with constant peritubular pH increased citrate reabsorption. Increasing perfusate pH to 7.6 decreased citrate reabsorption insignificantly (0.1 less than P less than 0.2). These data suggest that luminal pH in the proximal tubule is an important determinant of alterations in citrate reabsorption with acid-base disorders. The effect of luminal pH on citrate reabsorption is probably due to a change in concentration of the transported ionic species, citrate2-.

Acetazolamide↗
PubMed2004

Expression of Na+-dependent citrate transport in a strongly metastatic human prostate cancer PC-3M cell line: regulation by voltage-gated Na+ channel activity.

Prostate is a unique organ which synthesizes and releases large amounts of citrate. It has been shown that in metastatic prostate cancer, the amount of citrate in prostatic fluid is significantly reduced, approaching the level normally found in blood. In our previous study, we characterized electrophysiologically the mechanism of citrate transport in a normal prostatic epithelial (PNT2-C2) cell line. It was concluded that the cells expressed a novel transporter carrying 1 citrate3- together with 4 K+, primarily out of cells. In the present study, we aimed similarly to characterize the mechanism(s) of citrate transport in a strongly metastatic human prostate cancer (PC-3M) cell line and to compare this with the previous data. Citrate transport in PC-3M cells was found to be both Na+ and K+ dependent. Intracellular application of citrate produced an outward current that was primarily K+ dependent whilst extracellular citrate elicited an inward current that was mainly Na+ dependent. The electrophysiological and pharmacological characteristics of the citrate outward current were similar to the K+-dependent citrate transporter found in the PNT2-C2 cells. On the other hand, the inward citrate current had a markedly different reversal potential, ionic characteristics, inhibitor profile and pH sensitivity. Preincubation of the PC-3M cells (24 or 48 h) with the voltage-gated Na+ channel (VGSC) blocker tetrodotoxin (TTX) significantly reduced the Na+ sensitivity of the citrate current, up-regulated VGSC mRNA expression but did not change the partial permeability of the membrane to Na+. It was concluded (a) that PC-3M cells express a K+-dependent transporter (carrying citrate outward), similar to that found in normal prostate epithelial cells, as well as (b) a Na+-dependent transporter (carrying citrate inward). The molecular nature of the latter was investigated by RT-PCR; the three known Na+-dependent citrate/dicarboxylate transporters could not be detected. VGSC activity, which itself has been associated with metastatic prostate cancer, had a differential effect on the two citrate transporters, down-regulating the expression of the Na+-dependent component whilst enhancing the K+-dependent citrate transporter.

Carrier Proteins↗
PubMed2005

Transport and metabolism of citrate by Streptococcus mutans.

Streptococcus mutans, a normal inhabitant of dental plaque, is considered a primary etiological agent of dental caries. Two virulence determinants of S. mutans are its acidogenicity and aciduricity (the ability to produce acid and the ability to survive and grow at low pH, respectively). Citric acid is ubiquitous in nature; it is a component of fruit juices, bones, and teeth. In lactic acid bacteria citrate transport has been linked to increased survival in acidic conditions. We identified putative citrate transport and metabolism genes in S. mutans, which led us to investigate citrate transport and metabolism. Our goals in this study were to determine the mechanisms of citrate transport and metabolism in S. mutans and to examine whether citrate modulates S. mutans aciduricity. Radiolabeled citrate was used during citrate transport to identify citrate metal ion cofactors, and thin-layer chromatography was used to identify metabolic end products of citrate metabolism. S. mutans was grown in medium MM4 with different citrate concentrations and pH values, and the effects on the growth rate and cell survival were monitored. Intracellular citrate inhibited the growth of the bacteria, especially at low pH. The most effective cofactor for citrate uptake by S. mutans was Fe(3+). The metabolic end product of citrate metabolism was aspartate, and a citrate transporter mutant was more citrate tolerant than the parent.

Biological Transport↗
PubMed1995

Mechanisms of biodegradation of metal-citrate complexes by Pseudomonas fluorescens.

Biodegradation of metal-citrate complexes by Pseudomonas fluorescens depends on the nature of the complex formed between the metal and citric acid. Bidentate Fe(III)-, Ni-, and Zn-citrate complexes were readily biodegraded, but the tridentate Cd- and Cu-citrate, and U-citrate complexes were not. The biodegradation of Ni- and Zn-citrate commenced after an initial lag period; the former showed only partial (70%) degradation, whereas the latter was completely degraded. Uptake studies with 14C-labeled citric acid and metal-citrate complexes showed that cells grown in medium containing citric acid transported free citric acid at the rate of 28 nmol min-1 and Fe(III)-citrate at the rate of 12.6 nmol min-1 but not Cd-, Cu-, Ni-, U-, and Zn-citrate complexes. However, cells grown in medium containing Ni- or Zn-citrate transported both Ni- and Zn-citrate, suggesting the involvement of a common, inducible transport factor. Cell extracts degraded Fe(III)-, Ni-, U-, and Zn-citrate complexes in the following order: The cell extract did not degrade Cd- or Cu-citrate complexes. These results show that the biodegradation of the U-citrate complex was limited by the lack of transport inside the cell and that the tridentate Cd- and Cu-citrate complexes were neither transported inside the cell nor metabolized by the bacterium.

Adaptation, Physiological↗
PubMed2002

Aluminum citrate uptake by immortalized brain endothelial cells: implications for its blood-brain barrier transport.

The objective was to further test the hypothesis that aluminum (Al) citrate transport across the blood-brain barrier is mediated by a monocarboxylate transporter (MCT). Speciation calculations showed that Al citrates were the predominant Al species under the conditions employed. Al citrate did not inhibit lactate uptake and was not taken up by the rat erythrocyte, suggesting it does not serve as an effective substrate for either MCT1 or the anion exchanger. Studies were conducted with b.End5 cells derived from mouse brain endothelial cells to identify the properties of the carrier(s) mediating Al citrate transport. Western blot analysis of b.End5 cells showed expression of the transferrin receptor and MCT1, but not MCT2 or MCT4. Uptake of Al citrate was approximately 70% faster than citrate. Citrate and Al citrate uptake were sodium independent. Citrate uptake increased at pH 6.9 compared to 7.4, whereas Al citrate uptake did not. Al citrate uptake was reduced by inhibitors of mitochondrial respiration and oxidative phosphorylation, suggesting ATP dependence, but not by ouabain, suggesting no role for Na/K-ATPase. Uptake was not affected by alpha-ketoglutarate or malonate, substrates for the dicarboxylate carrier. Many substrates and inhibitors of MCT1 and organic anion transporters reduced Al citrate uptake into b.End5 cells. BSP and fluorescein, organic anion transporter substrates/inhibitors, inhibited Al citrate uptake. We conclude that Al citrate transport across the blood-brain barrier is carrier-mediated, involving either an uncharacterized MCT isoform expressed in the brain such as MCT7 or MCT8 and/or one of the many members of the organic anion transporting protein family, some of which are known to be expressed at the blood-brain barrier.

Aluminum↗
PubMed2003

Glucose prevents citrate metabolism by enterococci.

Enterococcus faecalis FAIR E-239, growing on glucose plus citrate, metabolized citrate at pH 6.5 or 7.5, but only when glucose had been exhausted; it did not metabolize citrate at pH 5.5 or 8.5. When grown on citrate only, the strain metabolized citrate at all pH values, and two growth rates were apparent. Citrate was mainly metabolized during the second, much slower growth rate. Glucose also inhibited citrate metabolism by E. faecalis FAIR E-237 and FAIR E-259 and Enterococcus faecium FAIR E-338 and FAIR E-371. Glucose-grown resting cells were unable to metabolize citrate. Citrate-grown resting cells had a pH optimum of 4.7 for citrate metabolism but also metabolized significant amounts of citrate at pH 4.2 and 6.5. Resting stationary phase cells used citrate more rapidly than resting log phase cells. Citrate metabolism was faster at citrate levels <10 mM than above 10 mM. These results suggest that some form of catabolite repression is occurring.

Citric Acid↗