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PubMed2005

CitI, a transcription factor involved in regulation of citrate metabolism in lactic acid bacteria.

A large variety of lactic acid bacteria (LAB) can utilize citrate under fermentative conditions. Although much information concerning the metabolic pathways leading to citrate utilization by LAB has been gathered, the mechanisms regulating these pathways are obscure. In Weissella paramesenteroides (formerly called Leuconostoc paramesenteroides), transcription of the citMDEFCGRP citrate operon and the upstream divergent gene citI is induced by the presence of citrate in the medium. Although genetic experiments have suggested that CitI is a transcriptional activator whose activity can be modulated in response to citrate availability, specific details of the interaction between CitI and DNA remained unknown. In this study, we show that CitI recognizes two A+T-rich operator sites located between citI and citM and that the DNA-binding affinity of CitI is increased by citrate. Subsequently, this citrate signal propagation leads to the activation of the cit operon through an enhanced recruitment of RNA polymerase to its promoters. Our results indicate that the control of CitI by the cellular pools of citrate provides a mechanism for sensing the availability of citrate and adjusting the expression of the cit operon accordingly. In addition, this is the first reported example of a transcription factor directly functioning as a citrate-activated switch allowing the cell to optimize the generation of metabolic energy.

Bacterial Proteins↗
PubMed2006

Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues.

BACKGROUND: In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism that is essential to prostate malignancy. The limiting m-aconitase activity in prostate epithelial cells could be the result of a decreased level of m-aconitase enzyme and/or the inhibition of existing m-aconitase. Earlier studies identified zinc as an inhibitor of m-aconitase activity in prostate cells; and that the depletion of zinc in malignant cells is an important factor in this metabolic transformation. However, a possibility remains that an altered expression and level of m-aconitase enzyme might also be involved in this metabolic transformation. To address this issue, the in situ level of m-aconitase enzyme was determined by immunohistochemical analysis of prostate cancer tissue sections and malignant prostate cell lines. RESULTS: The immunocytochemical procedure successfully identified the presence of m-aconitase localized in the mitochondrial compartment in PC-3, LNCaP, and DU-145 malignant prostate cell lines. The examination of prostate tissue sections from prostate cancer subjects demonstrated that m-aconitase enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocrcinomatous glands, and prostatic intraepithelial neoplastic foci. Quantitative analysis of the relative level of m-aconitase in the glandular epithelium of citrate-producing adenomatous glands versus the citrate-oxidizing adenocarcinomatous glands revealed no significant difference in m-aconitase enzyme levels. This is in contrast to the down-regulation of ZIP1 zinc transporter in the malignant glands versus hyperplastic glands that exists in the same tissue samples. CONCLUSION: The results demonstrate the existence of m-aconitase enzyme in the citrate-producing glandular epithelial cells; so that deficient m-aconitase enzyme is not associated with the limiting m-aconitase activity that prevents citrate oxidation in these cells. The level of m-aconitase is maintained in the malignant cells; so that an altered enzyme level is not associated with the increased m-aconitase activity. Consequently, the elevated zinc level that inhibits m-aconitase enzyme is responsible for the impaired citrate oxidation in normal and hyperplastic prostate glandular epithelial cells. Moreover, the down-regulation of ZIP1 zinc transporter and corresponding depletion of zinc results in the increase in the activity of the existing m-aconitase activity in the malignant prostate cells. The studies now define the mechanism for the metabolic transformation that characterizes the essential transition of normal citrate-producing epithelial cells to malignant citrate-oxidizing cells.

Aconitate Hydratase↗
PubMed1996

The number of follicles and ovarian volume in the assessment of response to clomiphene citrate treatment in polycystic ovarian syndrome.

OBJECTIVE: To evaluate whether the number of follicles and ovarian volume have any significance in evaluating the response to clomiphene citrate treatment in polycystic ovarian syndrome (PCOS). DESIGN: A prospective study of 70 infertile women, 44 of which were diagnosed with polycystic ovarian syndrome. MAIN OUTCOME MEASURES: Follicle numbers and volumes in both ovaries, hormonal profile, response to Clomiphene Citrate(CC). RESULTS: Ovarian volume was significantly greater in cases with polycystic ovarian syndrome than controls. However, ovarian volume in the Clomiphene Citrate nonresponders was significantly greater than in Clomiphene Citrate responders in the polycystic ovarian syndrome group. The number of small follicles was significantly higher in cases with polycystic ovarian syndrome than controls, and in the Clomiphene Citrate nonresponder group this number was also significantly higher than in Clomiphene Citrate responders. Endocrine features of patients with polycystic ovarian syndrome revealed that Dehydroepiandrostenedione sulfate, Androstenedione, follicle stimulating and luteinizing hormone do not discriminate between patients who respond to Clomiphene Citrate and those who do not respond. However, Testosterone and luteinizing hormone levels differ significantly in responders and nonresponders. CONCLUSIONS: Small multiple follicles (> 9) and enlarged ovarian volume (> 6.8 ml) were the most prominent transvaginal ultrasonographic features of ovaries in Clomiphene Citrate nonresponsive patients with polycystic ovarian syndrome. Higher levels of Testosterone, luteinizing hormone and significantly higher number of small follicles were associated with lack of Clomiphene Citrate response. These ultrasonographic features and laboratory assays could be clinically useful for distinguishing better the Clomiphene Citrate nonresponders from responders.

Adult↗
PubMed1999

Ranitidine bismuth citrate and clarithromycin, alone or in combination, for eradication of Helicobacter mustelae infection in ferrets.

OBJECTIVE: To determine whether ranitidine bismuth citrate, clarithromycin, or a combination of ranitidine bismuth citrate and clarithromycin would be efficacious in eradication of Helicobacter mustelae infection in ferrets. ANIMALS: 60 seven-month-old ferrets. PROCEDURE: To determine dosages of clarithromycin and ranitidine bismuth citrate that would suppress growth of, but not eradicate infection with, H mustelae, ferrets (n = 6/group) were treated p.o. with clarithromycin or ranitidine bismuth citrate at various dosages. Efficacy of treatment was then determined by treating ferrets with clarithromycin alone, ranitidine bismuth citrate alone, or clarithromycin and ranitidine bismuth citrate. Gastric biopsy specimens were obtained before, during, and at various times after treatment and submitted for quantitative bacterial culture and histologic evaluation. Minimum concentrations of clarithromycin that inhibited 90% of the growth of isolates obtained before and after treatment were determined. RESULTS: Dosages of clarithromycin and ranitidine bismuth citrate that suppressed growth of H mustelae were 12.5 and 24 mg/kg of body weight, p.o., every 8 hours, respectively. Infection was not eradicated in ferrets treated with ranitidine bismuth citrate alone but was eradicated in all 6 ferrets treated with clarithromycin and ranitidine bismuth citrate and in 4 of 6 treated with clarithromycin alone. A decrease in susceptibility to clarithromycin was detected for H mustelae isolates obtained after treatment. Mild or moderate antral gastritis was observed even in ferrets from which infection was eradicated. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of ranitidine bismuth citrate and clarithromycin was efficacious in eradicating H mustelae infection from ferrets.

Animals↗
PubMed2000

Cardioplegic strategies for calcium control: low Ca(2+), high Mg(2+), citrate, or Na(+)/H(+) exchange inhibitor HOE-642.

BACKGROUND: Ca(2+) overload plays an important role in the pathogenesis of cardioplegic ischemia-reperfusion injury. The standard technique to control Ca(2+) overload has been to reduce Ca(2+) in the cardioplegic solution (CP). Recent reports suggest that Na(+)/H(+) exchange inhibitors can also prevent Ca(2+) overload. We compared 4 crystalloid CPs that might minimize Ca(2+) overload in comparison with standard Mg(2+)-containing CP: (1) low Ca(2+) CP (0.25 mmol/L), (2) citrate CP/normal Mg(2+) (1 mmol/L Mg(2+)), (3) citrate CP/high Mg(2+) (9 mmol/L Mg(2+)), and (4) the addition of the Na(+)/H(+) exchange inhibitor HOE-642 (Cariporide). We also tested the effect of citrate titration in vitro on the level of free Ca(2+) and Mg(2+) in CPs. METHODS AND RESULTS: Isolated working rat heart preparations were perfused with oxygenated Krebs-Henseleit buffer and subjected to 60 minutes of 37 degrees C arrest and reperfusion with CPs with different Ca(2+) concentrations. Cardiac performance, including aortic flow (AF), was measured before and after ischemia. Myocardial high-energy phosphates were measured after reperfusion. The in vitro addition of citrate to CP (2%, 21 mmol/L) produced parallel reductions in Mg(2+) and Ca(2+). Because only Ca(2+) was required to be low, the further addition of Mg(2+) increased free Mg(2+), but the highest level achieved was 9 mmol/L. Citrate CP significantly impaired postischemic function (AF 58.3+/-2. 5% without citrate versus 41.6+/-3% for citrate with normal Mg(2+), P:<0.05, versus 22.4+/-6.2% for citrate with high Mg(2+), P:<0.05). Low-Ca(2+) CP (0.25 mmol/L Ca(2+)) significantly improved the recovery of postischemic function in comparison with standard CP (1.0 mmol/L Ca(2+)) (AF 47.6+/-1.7% versus 58.3+/-2.5%, P:<0.05). The addition of HOE-642 (1 micromol/L) to CP significantly improved postischemia function (47.6+/-1.7% without HOE-642 versus 62.4+/-1. 7% with HOE-642, P:<0.05). Postischemia cardiac high-energy phosphate levels were unaffected by Ca(2+) manipulation. CONCLUSIONS: (1) A lowered Ca(2+) concentration in CP is beneficial in Mg(2+)-containing cardioplegia. (2) The use of citrate to chelate Ca(2+) is detrimental in the crystalloid-perfused isolated working rat heart, especially with high Mg(2+). (3) The mechanism of citrate action is complex, and its use limits precise simultaneous control of Ca(2+) and Mg(2+). (4) HOE-642 in CP is as efficacious in preservation of the ischemic myocardium as is the direct reduction in Ca(2+).

Adenosine Diphosphate↗
PubMed1982

[Comparison of 201T1-chloride and 67Ga-citrate in thyroid tumor scintigraphy].

Twenty-five patients with thyroid tumors were examined by 201T1-chloride and 67Ga-citrate scintigraphy heterochronously in our department. All cases showed the cold nodule with 131I or 99mTc-pertechnetate thyroid scintigraphy and each one was given a histological diagnosis after surgery or excisional biopsy. In 15 cases of thyroid carcinoma, 12 (80%) were positive by 201T1-chloride; 4 (26.7%) were positive by 67Ga-citrate. In examining each histological type, 8 of 9 cases of papillary carcinoma (88.9%) were positive by 201T1-chloride. In 1 negative case the tumor was almost completely encysted; however, they were all negative by 67Ga-citrate. In 2 patients with follicular carcinoma, both of them revealed a positive figure by 201T1-chloride, and one of these with oxyphilic cell carcinoma showed a positive figure by 67Ga-citrate. In 1 case of medullary carcinoma there was slight accumulation with 201T1-chloride, but there was no accumulation with 67Ga-citrate. In 3 cases of undifferentiated carcinoma, 2 patients with small carcinoma showed a negative figure by 201T1-chloride. However, they all showed a positive figure using 67Ga-citrate and this medium also disclosed distant metastases of undifferentiated carcinoma. In 10 patients with thyroid adenoma, 3 (30%) showed a positive figure by 201T1-chloride. Histologically, these were all tubular adenoma, but in all cases of thyroid adenoma 67Ga-citrate revealed a negative figure. From the above mentioned results, the following conclusion were reached. Tumors showing a positive figure by 201T1-chloride that elicited negative results using 67Ga-citrate proved to be differentiated carcinoma or low differentiated types of adenoma. Surgery is indicated in these cases. All of the tumors revealing a positive figure by 67Ga-citrate were highly malignant types. If these tumors showed a negative figure when 201T1-chloride was used, undifferentiated carcinoma was suggested. In undifferentiated carcinoma, 67Ga-citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy.

Adenocarcinoma↗
PubMed2000

A comparison of two sodium citrate concentrations in two evacuated blood collection systems for prothrombin time and ISI determination.

The prothrombin time is usually measured in citrated plasma. The W.H.O. recommended concentration of sodium citrate for blood collection for laboratory control of oral anticoagulant therapy is 0.109 M. Some evacuated blood collection systems include 0.105 M sodium citrate. The purpose of the present study was to establish the difference in ISI calibration between 0.109 and 0.105 M citrate, using 7 types of thromboplastin and various types of instrumentation. The two citrate concentrations were provided in both evacuated siliconised glass tubes and in evacuated polyethylene terephtalate (PET) tubes. The ISI difference between the two citrate concentrations was 5.4% for one system but not greater than 3% for all other systems when blood samples were collected with either siliconized glass or PET tubes. Most of the ISI differences between the two citrate concentrations were not significant at the 5% level. It is concluded that the ISI differences between 0.105 M and 0.109 M citrate are not of practical importance. In contrast, ISI differences between siliconised glass and PET tubes, using either 0.105 or 0.109 M citrate, were significant (p <0.05) for most thromboplastin systems and amounted to 7%. ISI interchange between these glass and PET tubes could induce INR differences amounting to 14%, which could affect clinical dosage of oral anticoagulants.

Blood Specimen Collection↗
PubMedDate not supplied

Immunological mapping of fine molecular surface structures of citrate synthase enzymes from different cell types.

Citrate synthase (EC 4.1.3.7), which is present in all living organisms as a key enzyme in aerobic energy metabolism, is one of the most highly phylogenetically conserved enzymes known in terms of its primary and active site structure. However, in terms of other parameters such as in vitro stability, tolerance to changes in pH, degree of self-polymerization, etc., citrate synthases from different sources are markedly different. These divergences can be observed even between isoforms of the enzyme within the same species. Data documenting these diversities suggest that a high degree of difference in tertiary structures may occur. Therefore, the surface profiles of citrate synthase enzymes from yeast, pig, rat, tomato and Escherichia coli were investigated with immunological methods using monoclonal antibody families generated against either pig citrate synthase (alpha-PCS) or yeast citrate synthase-2 (alpha-YCS-2). A high degree of homology of enzyme epitopes was detected on the mitochondrial citrate synthases originating from yeast, tomato, pig and rat cells. Major differences were found between the hexameric citrate synthase originating from E. coli compared with those dimeric forms prepared from eukaryotic cells. Only modest similarities were detected between the highly homologous peroxisomal and mitochondrial yeast citrate synthases. Furthermore, a point mutation of one of the catalytic residues (H274R on recombinant pig and H313R on yeast enzyme) of mitochondrial citrate synthase (CS-1) resulted in a significant increase in immunological similarity with the peroxisomal isoenzyme (CS-2). These findings are discussed in terms of the possible mechanism of evolution of CS-2 in yeast.

Animals↗
PubMed1989

Prostate epithelial cells utilize glucose and aspartate as the carbon sources for net citrate production.

The prostate gland (human, rat ventral prostate) has the major function of accumulating and secreting extremely high levels of citrate. This function requires unique and specialized metabolic pathways associated with prostate secretory epithelial cells by which exogenous substrates must be utilized as the six-carbon sources of citrate. Recent studies demonstrated that aspartate can serve as the four-carbon source of oxalacetate for citrate synthesis. Identification of the two-carbon source of acetyl CoA (AcCoA) had not been established. The present study investigated the probability that exogenous glucose, via pyruvate oxidation, is a physiological source of AcCoA for net citrate production by isolated epithelial cells from rat ventral prostate. Under adequate oxygenation, 5 mM glucose in the presence of aspartate plus glutamate markedly stimulated citrate production. Exogenous and endogenous pyruvate also stimulated net citrate production. We propose that glucose via aerobic glycolysis and pyruvate oxidation provides AcCoA, which condenses with oxalacetate obtained from aspartate transamination for citrate synthesis. Prostate epithelial cells do not readily oxidize citrate, which permits accumulation and secretion of the synthesized citrate.

Acetyl Coenzyme A↗
PubMed1975

Citrate lyase from Streptococcus diacetilactis. Association with its acetylating enzyme.

Citrate lyase (EC 4.1.3.6) was purified 38-fold from cell-free extracts of Streptococcus diacetilactis. The enzyme was homogeneous in analytical ultracentrifugation and polyacrylamide gel electrophoresis. The final enzyme preparation contained acetate: HS-citrate lyase ligase--an acetylating enzyme which converts inactive HS-citrate lyase into enzymatically active acetyl-S-citrate lyase. This enzyme activity was purified 25-fold over the crude extract and seemed to be associated with citrate lyase. Partially purified citrate lyase from Leuconostoc citrovorum contained also its acetylating enzyme. Purified citrate lyases from Klebsiella aerogenes and Rhodopseudomonas gelatinosa were devoid of acetylating enzyme activity. The HS-form of citrate lyase from S. diacetilactis was completely acetylated and hence activated by incubation with ATP and acetate for 25 min at 25 degrees C. The enzyme did not acetylate the HS-lyases from R. gelatinosa and K. aerogenes. In contrast to the citrate lyases from R. gelatinosa and K. aerogenes the enzymes from S. diacetilactis and L. citrovorum showed only a very weak reaction inactivation. It is assumed that this is due to the association of the acetylating enzymes with these lyases.

Acetates↗
PubMed1975

Intrarenal distribution of citrate in the dog during antidiuresis and diuresis.

The intrarenal distribution of citrate was evaluated in the dog during antidiuresis and osmotic diuresis, by using the specific citrate assay method of Moellering and Gruber. The measurements were made on tissue samples taken from four different regions throughout the kidney: cortex, outer and inner medulla, and papilla. During antidiuresis, a characteristic distribution of citrate was observed with highest levels in the papilla and lowest ones in the outer medulla. A medullary concentration gradient for citrate was found. Mannitol greatly decreased papillary citrate and sodium, but no changes in outer and inner medullary citrate occured. The results could not be explained by the citrate contained either in the trapped urine or blood in the tissue. It is suggested that citrate accumulation in the inner regions of renal medulla may be accounted for by countercurrent mechanisms or regional differences in renal citrate metabolism.

Animals↗
PubMed1983

Pancreatic citrate and protein secretion of alcoholic dogs in response to graded doses of caerulein.

Previous studies have shown dissolution of human pancreatic stones in vitro by citrate solution which bind considerable amounts of ionized calcium. Pancreatic citrate secretion has been demonstrated in canine and human pancreatic juices. This study compares pancreatic citrate secretion of chronic alcohol-fed dogs with controls in response to graded doses of caerulein, in order to evaluate possible differences in factors favouring pancreatic lithogenicity. The dose-response-relation of citrate outputs after graded doses of caerulein revealed significantly reduced maximal secretory capacity of citrate in alcoholic dogs. Protein concentrations in juices from alcoholic dogs were reduced for all doses of caerulein but protein outputs were not different. Bicarbonate concentrations and outputs, as well as volumes, were significantly greater in alcoholic dogs. Linear relation were found between citrate and protein secretion. Chronic alcohol consumption in the dog leads to reduced citrate secretion, which is consistent with recent results in humans suffering from chronic calcifying pancreatitis, who secrete significantly less citrate than healthy subjects. The decrease of calcium-chelating citrate could be an additional factor causing increased calcium levels in the pancreatic juice of chronic alcoholics, a circumstance that might favour protein-plug formation and subsequently pancreatic stone formation.

Alcoholism↗
PubMed2001

A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria.

For many years, urine alkalinization has been one of the cornerstones in the treatment of homozygous cystinuria. Because of the relationship found between the excretion of urinary sodium and cystine, potassium citrate has emerged as the preferred sodium-free alkalizing agent. To evaluate the usefulness of potassium citrate for urine alkalization in cystinuric patients, sodium bicarbonate and potassium citrate were compared in 14 patients (10 on tiopronin treatment and four without treatment with sulfhydryl compounds). The study started with 1 week without the use of any alkalizing agents (Period 0) followed by 2 weeks with sodium bicarbonate (Period 1) and 2 weeks with potassium citrate (Period 2). Urinary pH, volume, excretion of sodium, potassium, citrate and free cystine, as well as the plasma potassium concentration, were recorded. Potassium citrate was shown to be effective as an alkalizing agent and, in this respect, not significantly different from sodium bicarbonate. Even though a normal diet was used, a significant increase in urinary sodium excretion was observed with sodium bicarbonate (Period 1). Urinary potassium and citrate excretion increased with potassium citrate (Period 2). A significant correlation was found between urinary sodium and cystine in the tio-pronin-treated patients. No significant differences in cystine excretion were recorded in Periods 0, 1 and 2. Plasma potassium was significantly higher during Period 2, but only one patient developed a mild hyperkalemia (5.0 mmol/l). The use of potassium citrate for urine alkalization in homozygous cystinuria is effective and can be recommended in the absence of severe renal impairment.

Adult↗
PubMed2003

Differential Al resistance and citrate secretion in barley (Hordeum vulgare L.).

While barley ( Hordeum vulgare L.) is the most sensitive species to Al toxicity among small-grain crops, variation in Al resistance between cultivars does exist. We examined the mechanism responsible for differential Al resistance in 21 barley varieties. Citrate was secreted from the roots in response to Al stress. A positive correlation between citrate secretion and Al resistance [(root elongation with Al)/(root elongation without Al)] and a negative correlation between citrate secretion and Al content of root apices, were obtained, suggesting that citrate secretion from the root apices plays an important role in excluding Al and thereby detoxifying Al. The Al-induced secretion of citrate was characterized using an Al-resistant variety (Sigurdkorn) and an Al-sensitive variety (Kearney). In Sigurdkorn, Al-induced secretion of citrate occurred within 20 min, and the secretion did not increase with increasing external Al concentration. The Al-induced citrate secretion ceased at low temperature (6 degrees C) and was inhibited by anion-channel inhibitors. Internal citrate content of root apices was increased by Al exposure in Sigurdkorn, but was not affected in Kearney. The activity of citrate synthase was unaffected by Al in both Al-resistant and Al-sensitive varieties. The secretion rate of organic acid anions from barley was the lowest among wheat, rye and triticale.

Adaptation, Physiological↗
PubMed1984

The role of sodium citrate in the dysfibrinogenaemia of liver disease.

The addition of excess sodium citrate to plasma was found to inhibit fibrin polymerisation (clot opacity) from patients with cirrhosis, hepatitis and hepatoma but not from normal controls. Abnormal clot opacity in plasma from patients with liver disease could be partly or completely abolished by removal of citrate ions by dialysis against citrate-free buffer, but not by dialysis against buffer containing citrate. Similar results were observed in plasma freed of calcium ions by treatment with EGTA. Treatment of plasma with neuraminidase largely abolished the inhibitory effect of excess citrate, and the thrombin times and clot opacity of asialofibrinogen were less affected by citrate than native fibrinogen. In addition, the effects of citrate on the clotting of purified, calcium-free fibrinogen from cirrhotic patients correlated with the sialic acid content. It is concluded that binding of citrate ions to fibrinogen renders the molecule acutely more sensitive to elevations in the sialic acid content, and that a simple plasma clot opacity test in the presence of excess citrate may be a useful aid in the differential diagnosis of liver disease. These findings may also explain why defects in fibrin polymerisation observed in plasma are not always reproduced in purified fibrinogen or fibrin monomer preparations.

Afibrinogenemia↗
PubMed1993

Can citrate therapy prevent nephrolithiasis?

This prospective study was done to help determine whether or not oral citrate therapy can elevate urinary citrate levels and reduce the incidence of recurrent calcium stones in patients with hypocitraturia (urinary citrate less than 320 mg/24 hr). The treatment group (Group I) consisted of 10 patients treated with oral citrate and hydration. The control group (Group II) was treated with hydration alone. In Group I, the new stone formation rate (stones per patient year) fell from 1.17 +/- 0.26 to 0.45 +/- 0.32 (p = 0.07) and the twenty-four-hour urinary citrate excretion rose from 69 +/- 14 mg to 473 +/- 96 mg (p = 0.002). In Group II, the new stone formation rate fell from 0.9 +/- 0.25 to 0.27 +/- 0.13 (p = 0.03). The twenty-four-hour urinary citrate excretion increased, though not significantly, from 166 +/- 21 mg to 326 +/- 77 mg (p = 0.06). We conclude that oral citrate therapy can significantly increase urinary citrate levels in patients with recurrent stones associated with hypocitraturia but that oral citrate therapy and hydration were no better than hydration alone in reducing the incidence of recurrent stones.

Calcium Oxalate↗
PubMed1990

Molybdenum cofactor negative mutants of Escherichia coli use citrate anaerobically.

Anaerobically, Escherichia coli cannot grow using either glycerol or citrate as sole carbon and energy source. However, it has been reported that a mixture of glycerol and citrate will support growth. We have found that wild-type strains of E. coli K-12 do not grow on glycerol plus citrate anaerobically. However, growth eventually occurs due to the frequent appearance of mutants. We found that such Cit+ mutants were defective in anaerobic respiration with nitrate or trimethylamine-N-oxide and were chlorate resistant (i.e. molybdenum cofactor deficient). Conversely, well characterized mutants in any of chlA, B, D, E, G and N were also able to use citrate anaerobically. No anaerobic growth differences between wild type and chl mutants were observed either with fermentable sugars or with glycerol plus fumarate or glycerol plus tartrate. Citrate lyase was induced anaerobically by citrate and repressed by glucose in both wild type strains and chl mutants. Furthermore, levels of citrate lyase, fumarate reductase, malate dehydrogenase, fumarase and alcohol dehydrogenase were similar in both types of strains under anaerobic conditions. It is conceivable that a functioning molybdenum cofactor prevents use of citrate by keeping citrate lyase in the inactive form.

Aconitate Hydratase↗
PubMed2005

Is regional citrate superior to systemic heparin anticoagulation for continuous renal replacement therapy? A prospective observational study in an adult regional critical care system.

PURPOSE: Continuous renal replacement therapy (CRRT) is commonly used in the care of critically ill patients although the optimal means of anticoagulation is not well defined. We report our regional CRRT protocol that was developed using the principles of quality improvement and compare the effect of regional citrate with systemic heparin anticoagulation on filter life span. MATERIALS AND METHODS: Prospective observational cohort study in a Canadian adult regional critical care system. A standardized protocol for CRRT has been implemented at all adult intensive care units in the Calgary Health Region since August 1999. All patients with acute renal failure treated with CRRT during October 1, 2002, to September 30, 2003, were identified and followed up prospectively until hospital discharge or death. RESULTS: Eighty-seven patients with acute renal failure requiring CRRT were identified, 54 were initially treated with citrate, 29 with heparin, and 4 with saline flushes. Citrate and heparin were used in 212 (66%) and 97 (30%) of filters for 8776 and 2651 hours of CRRT, respectively. Overall median (interquartile range) filter life span with citrate was significantly greater than heparin (40 [14-72] vs 20 [5-44] hours, P < .001). The median time to spontaneous filter failure was significantly greater with citrate compared with heparin (>72 vs 33 hours, P < .001). Citrate anticoagulation resulted in greater completion of scheduled filter life span (59% vs 10%, P > .001). Citrate anticoagulation was well tolerated with no patient requiring elective discontinuation for hypernatremia, metabolic alkalosis, or hypocalcemia. CONCLUSIONS: Regional citrate anticoagulation was associated with prolonged filter survival and increased completion of scheduled filter life span compared with heparin. These data support small studies suggesting that citrate is a superior anticoagulant for CRRT and suggest the need for a future definitive randomized controlled trial.

Acute Kidney Injury↗