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PubMed2001

Sildenafil citrate effectively reverses sexual dysfunction induced by three-dimensional conformal radiation therapy.

OBJECTIVES: We evaluated the response of sildenafil citrate in patients with prostate cancer treated with three-dimensional conformal radiation therapy (3DCRT) whose sexual function (SF) was known prior to therapy initiation. METHODS: From March 1996 to April 1999, 24 men with median age of 68 years (range 51 to 77) had 3DCRT for localized prostate cancer (median prescribed dose to the planning target volume of 70.2 Gy). These men started taking sildenafil for relief of sexual dysfunction at a median time of 1 year after completing 3DCRT. We used the self-administered O'Leary Brief Sexual Function Inventory to evaluate in series SF and overall satisfaction at three time points. These points were (a) before initiation of all therapies (3DCRT or hormonal treatment [HT]) for prostate cancer, (b) before starting sildenafil (50 mg or 100 mg) but after completion of all therapies, and (c) at least 2 months afterward. Rates of SF were based on the number of men responding to a given question. We tested for significance of these two interventions to change SF by applying the Wilcoxon sign rank test. RESULTS: Prior to all treatments, 20 (87%) of 23 men were sexually potent, with 8 (36%) of 22 fully potent (little or no difficulty for penetration at intercourse). After 3DCRT with or without HT and prior to sildenafil use, 13 (65%) of the 20 potent patients remained potent, with only 2 (11%) of 19 being fully potent. The use of sildenafil citrate resulted in 21 (91%) of 23 men being potent, with 7 (30%) being fully potent. In 16 men responding to the satisfaction question, 10 (63%) and 12 (75%) were mixed to very satisfied with their sex life before 3DCRT with or without HT and after sildenafil citrate use, respectively. This response corresponded to potency and satisfaction scores significantly decreasing and subsequently increasing on average by one unit after 3DCRT and sildenafil citrate use, respectively (P <0.05). CONCLUSIONS: In men receiving 3DCRT for prostate cancer, these data indicate that sildenafil citrate is effective for restoring SF and associated satisfaction back to baseline before treatment.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1985

Efficacy of activated charcoal and magnesium citrate in the treatment of oral paraquat intoxication.

The binding capacity of activated charcoal for paraquat was evaluated in vitro and in vivo and compared with Fuller's earth. In vitro activated charcoal absorbs paraquat and is as effective as Fuller's earth. Activated charcoal's absorbing capacity for paraquat is increased when it is suspended in magnesium citrate and is maximal at pH 7.8. Paraquat (200 mg/kg) administered orally to male mice, followed 30 minutes later by activated charcoal, Fuller's earth (4 gm/kg), and magnesium citrate (0.01 cc/gm) resulted in a survival rate of 31% in the controls, 63% in the activated charcoal and Fuller's earth groups, and 69% in the magnesium citrate group (P values not significant). When activated charcoal was administered concomitantly with magnesium citrate, the survival rate was improved significantly to 94% (P less than 0.01). The efficacy and greater availability of activated charcoal and magnesium citrate make these materials the treatment of choice for gastrointestinal decontamination in oral paraquat poisoning.

Absorption↗
PubMed1991

Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide.

The effect of calcium citrate on intestinal aluminum absorption, assessed by the increment in urinary aluminum excretion, was evaluated in eight normal men. Baseline urinary aluminum excretion was determined for 2 days; thereafter, subjects ingested aluminum hydroxide for 3 days. In a cross-over study, subjects were given either calcium citrate, 950 mg four times a day, or placebo during the 3 days of aluminum hydroxide ingestion (2.4 g/d). Plasma aluminum levels were measured on the second control day and the third day of aluminum hydroxide ingestion. Baseline urinary aluminum excretion was 0.02 +/- 0.004 (6.5 +/- 1.1 micrograms/g creatinine) and 0.03 +/- 0.005 mumol/mmol creatinine (7.4 +/- 1.3 micrograms/g creatinine). These values increased during aluminum hydroxide therapy, but values were much greater when calcium citrate was ingested with aluminum hydroxide. On 3 consecutive days, urinary aluminum excretion levels were 11.1 +/- 3.23, 8.8 +/- 2.9, and 5.3 +/- 0.7 times greater during the administration of calcium citrate with aluminum hydroxide than with aluminum hydroxide alone. Plasma aluminum levels did not differ in the two treatment groups. Thus, calcium citrate markedly enhances the absorption of aluminum from aluminum hydroxide and the two must not be prescribed together in patients with renal failure.

Adult↗
PubMed1991

[Comparative effects of diazepam, ranitidine , sodium citrate and enprostil on pH and gastric volume in preanesthetic medication].

A study was designed to assess the efficacy of oral premedication with diazepam or enprostil in preventing the gastric aspiration syndrome in fasted patients scheduled for elective surgery, and to compare the results with those obtained with ranitidine and sodium citrate. The study included 120 consecutive patients undergoing urological or plastic surgery, randomly assigned to four groups of 30. Two hours before anaesthesia, the patients from three groups were given, with 30 ml of water, either 10 mg diazepam, or 150 mg ranitidine, or 35 micrograms enprostil. Those in the fourth group were given 30 ml of 0.5 M sodium citrate, ten minutes before induction. Anaesthesia consisted in the administration of thiopentone, fentanyl, vecuronium and nitrous oxide in oxygen. After endotracheal intubation, a gastric tube was inserted. The stomach fluid content was completely aspirated, and then again 60 and 120 min after induction, as well as at the end of surgery. Age, weight and duration of surgery were comparable in the four groups. Mean pH in the diazepam group was much lower than that in the other groups, both just after induction (2.3 +/- 1.54; p less than 0.001 vs. ranitidine and sodium citrate; p less than 0.01 vs. enprostil) and at the end of surgery (3.2 +/- 2.03; p less than 0.01 vs. ranitidine and sodium citrate; p less than 0.05 vs. enprostil). There was more than 0.4 ml.kg-1 gastric juice in the sodium citrate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antacids↗
PubMed1998

Structural adaptations of the cold-active citrate synthase from an Antarctic bacterium.

BACKGROUND: The structural basis of adaptation of enzymes to low temperature is poorly understood. Dimeric citrate synthase has been used as a model enzyme to study the structural basis of thermostability, the structure of the enzyme from organisms living in habitats at 55 degrees C and 100 degrees C having previously been determined. Here the study is extended to include a citrate synthase from an Antarctic bacterium, allowing us to explore the structural basis of cold activity and thermostability across the whole temperature range over which life is known to exit. RESULTS: We report here the first crystal structure of a cold-active enzyme, citrate synthase, isolated from an Antarctic bacterium, at a resolution of 2.09 A. In comparison with the same enzyme from a hyperthermophilic host, the cold-active enzyme has a much more accessible active site, an unusual electrostatic potential distribution and an increased relative flexibility of the small domain compared to the large domain. Several other features of the cold-active enzyme were also identified: reduced subunit interface interactions with no intersubunit ion-pair networks; loops of increased length carrying more charge and fewer proline residues; an increase in solvent-exposed hydrophobic residues; and an increase in intramolecular ion pairs. CONCLUSIONS: Enzymes from organisms living at the temperature extremes of life need to avoid hot or cold denaturation yet maintain sufficient structural integrity to allow catalytic efficiency. For hyperthermophiles, thermal denaturation of the citrate synthase dimer appears to be resisted by complex networks of ion pairs at the dimer interface, a feature common to other hyperthermophilic proteins. For the cold-active citrate synthase, cold denaturation appears to be resisted by an increase in intramolecular ion pairs compared to the hyperthermophilic enzyme. Catalytic efficiency of the cold-active enzyme appears to be achieved by a more accessible active site and by an increase in the relative flexibility of the small domain compared to the large domain.

Amino Acid Sequence↗
PubMed1988

Radiolabeled porphyrin vs gallium-67 citrate for the detection of human melanoma in athymic mice.

We performed the biodistribution and imaging studies of 111In and 67Ga labeled tetra(4-N-methylpyridyl)porphine, (T4NMPYP), and compared it to that of 67Ga-citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111In and 67Ga labeled T4NMPYP (3, 6, 24 and 48 h) were similar but differed from that of 67Ga-citrate (48 h). The optimum tumor uptake of both radiolabeled porphyrins was at 6 h post-injection and was lower than the tumor uptake of 67Ga-citrate at 48 h post-injection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67Ga-citrate. The imaging studies performed with 111In-T4NMPYP and 67Ga-citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111In-T4NMPYP.

Animals↗
PubMedDate not supplied

Acute biochemical variations induced by calcium citrate and calcium carbonate in Type 2 diabetic patients: impaired calcium absorption in Type 2 diabetic patients with prolonged gastric emptying time.

Calcium supplementation is important in the treatment of osteoporosis, a disease that may also occur in diabetic patients. The acute effects of calcium supplementation and their relationship to gastric emptying time, however, have rarely been studied in type 2 diabetic patients. We evaluated the acute biochemical variations induced by the administration of two different calcium preparations, calcium citrate and calcium carbonate, in 16 (male/female: 13/3) Chinese diabetic patients. Serum free calcium, intact parathyroid hormone (i-PTH), and amount of urinary excretion of calcium (uCal/uCr) were evaluated after a single dose of 1200 mg of elemental calcium in each preparation. The free calcium levels did not change significantly in either group. However, significant suppression of i-PTH after calcium citrate administration at 1 h (17.1+/-2.0 pg/ml, P=.023), and after calcium carbonate administration at 2 h (14.2+/-2.5 pg/ml, P=.000), was noted when compared with individual basal level (21.2+/-2.5 and 19.3+/-2.4 pg/ml, respectively). The suppressive effect on i-PTH lasted for 6 h after calcium citrate and 5 h after calcium carbonate preparation of the 6-h study period. After administration of calcium citrate, the uCal/uCr of 2-to-4-h collection was significantly higher than that of the basal and 0-to-2-h collections: 0.25+/-0.04 vs. 0.19+/-0.03, P=.025; and 0.25+/-0.04 vs. 0.19+/-0.02, P=.014, respectively. A similar finding was observed for calcium carbonate: 0.23+/-0.03 vs. 0.18+/-0.02, P=.019; and 0.23+/-0.03 vs. 0.18+/-0.02, P=.011, respectively. We conclude that, in this group of Chinese type 2 diabetic patients in our study, the oral administration of 1200 mg elemental calcium in either calcium citrate or calcium carbonate preparation can induce a significant suppression of i-PTH. This may be helpful in preventing or treating osteoporosis. A prolonged gastric emptying time in these diabetic subjects may contribute to the non-significant alteration in free calcium levels after the administration of either calcium preparation.

Administration, Oral↗
PubMed1993

Concentration of citrate in the mammary secretion of sows during lactogenesis II and established lactation.

The functional significance of citrate in the mammary secretion of six sows was investigated during the second stage of lactogenesis (lactogenesis II) and established lactation. The changes in the concentrations of progesterone and lactose in the maternal blood, and lactose, Na and K in the mammary secretion, suggested that lactogenesis II began during the final day of pregnancy. The concentration of citrate in the mammary secretion of the sows during lactogenesis II was high and varied from 5.4 (SEM 0.5) mM at day 0.5 post partum to 6.8 (SEM 0.4) mM at day 1.5 post partum. There was a decline of approximately 30% in the concentration of citrate in the milk of sows during the first week of lactation. These findings suggest that, in contrast to all other species studied previously, milk citrate is not a harbinger of lactogenesis II in the sow. However, the changes in the concentration of citrate in the mammary secretions of sows may reflect changes in the rate of de novo synthesis of fatty acids that take place in the mammary glands of sows during lactogenesis II and established lactation.

Animals↗
PubMed1994

An anion binding site in human aldose reductase: mechanistic implications for the binding of citrate, cacodylate, and glucose 6-phosphate.

Aldose reductase is a NADPH-dependent aldo-keto reductase involved in the pathogenesis of some diabetic and galactosemic complications. The published crystal structure of human aldose reductase [Wilson et al. (1992) Science 257, 81-84] contains a hitherto unexplained electron density positioned within the active site pocket facing the nicotinamide ring of the NADPH and other key active site residues (Tyr48, His110, and Cys298). In this paper we identify the electron density as citrate, which is present in the crystallization buffer (pH 5.0), and provide confirmatory evidence by both kinetic and crystallographic experiments. Citrate is an uncompetitive inhibitor in the forward reaction with respect to aldehyde (reduction of aldehyde), while it is a competitive inhibitor with respect to alcohol in the backward reaction (oxidation of alcohol), indicating that it interacts with the enzyme-NADP(+)-product complex. Citrate can be replaced in the crystalline enzyme complex by cacodylate or glucose 6-phosphate; the structure of each of these complexes shows the specific molecule bound in the active site. All of the structures have been determined to a nominal resolution of 1.76 A and refined to R-factors below 18%. While cacodylate can be bound within the active site under the crystallization conditions, it does not inhibit the wild-type enzyme in solution. Glucose 6-phosphate, however, is a substrate for aldose reductase. The similar location of the negative charges of citrate, cacodylate, and glucose 6-phosphate within the active site suggests an anion-binding site delineated by the C4N of nicotinamide, the OH of Tyr48, and the N epsilon of His110. The location of citrate binding in the active site leads to a plausible catalytic mechanism for aldose reductase.

Aldehyde Reductase↗
PubMed1991

Crystal structure of an open conformation of citrate synthase from chicken heart at 2.8-A resolution.

The X-ray structure of a new crystal form of chicken heart muscle citrate synthase, grown from solutions containing citrate and coenzyme A or L-malate and acetyl coenzyme A, has been determined by molecular replacement at 2.8-A resolution. The space group is P4(3) with a = 58.9 A and c = 259.2 A and contains an entire dimer of molecular weight 100,000 in the asymmetric unit. Both "closed" conformation chicken heart and "open" conformation pig heart citrate synthase models (Brookhaven Protein Data Bank designations 3CTS and 1CTS) were used in the molecular replacement solution, with crystallographic refinement being initiated with the latter. The conventional crystallographic R factor of the final refined model is 19.6% for the data between 6- and 2.8-A resolution. The model has an rms deviation from ideal values of 0.034 A for bond lengths and of 3.6 degrees for bond angles. The conformation of the enzyme is essentially identical with that of a previously determined "open" form of pig heart muscle citrate synthase which crystallizes in a different space group, with one monomer in the asymmetric unit, from either phosphate or citrate solution. The crystalline environment of each subunit of the chicken enzyme is different, yet the conformation is the same in each. The open conformation is therefore not an artifact of crystal packing or crystallization conditions and is not species dependent. Both "open" and "closed" crystal forms of the chicken heart enzyme grow from the same drop, showing that both conformations of the enzyme are present at equilibrium in solution containing reaction products or substrate analogues.

Amino Acid Sequence↗
PubMed1987

Amino acid sequence at the citrate allosteric site of rabbit muscle phosphofructokinase.

Previously, this laboratory has demonstrated [Colombo, G., & Kemp, R. G. (1976) Biochemistry 15, 1774-1780] that under appropriate conditions the citrate inhibitory binding site of rabbit skeletal muscle phosphofructokinase can be covalently modified by using pyridoxal phosphate and sodium borohydride. In the current study, phosphofructokinase was modified by [3H]pyridoxal phosphate and sodium borohydride with or without the addition of citrate to protect the ligand binding site. The modified proteins were digested with trypsin, and the peptides were separated by high-pressure liquid chromatography. A comparison of the tryptic chromatographic profiles showed that while the label was broadly distributed among nine peaks in the elution profile of the enzyme modified in the presence of the protective ligand, a single peptide contained 70% of the total radioactivity of the enzyme modified in the absence of citrate. This peptide was presumed to contain at least part of the citrate inhibitory site of the enzyme. The sequence of the peptide was determined and shown to match with positions 528-536 of phosphofructokinase with the modified residue being Lys-529. A comparison of the sequence with that of procaryotic phosphofructokinase indicated that a homologous residue in the enzyme from Bacillus stearothermophilis is critical to an allosteric site. A second peptide that was the most abundant labeled peptide in the digest of the enzyme modified in the presence of citrate was found to be identical with the second most abundant peptide of the digest from the unprotected enzyme. This peptide corresponded to residues 681-692 with the lysine at position 684 being the site of phosphopyridoxylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Site↗
PubMed1980

Limited proteolysis of pig heart citrate synthase by subtilisin, chymotrypsin, and trypsin.

Pig heart citrate synthase was subjected to limited proteolytic attack by subtilisin, chymotrypsin, and trypsin in the presence of palmitoyl-CoA. Initial proteolysis by all three proteolytic enzymes resulted in cleavage of the monomeric subunit (Mr 45 000 +/- 3000) into a large (Mr 35 000-38 500) and a small (Mr 9000 +/- 3000) into a large (Mr 35 000-38 500) and a small (Mr 9000-12 000) fragment. Further proteolysis of the large subunit produced a secondary fragment (Mr 31 000-36 000). The small (Mr 9000-12 000) fragment was stable in the presence of subtilisin but was substantially degraded by both chymotrypsin and trypsin. The actual molecular weight of fragments varied with the choice of the proteolytic enzyme. Limited proteolysis was absolutely dependent on the presence of palmitoyl-CoA and resulted in complete inhibition of the catalytic activity of the enzyme. Citrate, ammonium sulfate, and especially oxaloacetate provided complete protection against proteolysis whereas acetyl-CoA, CoASH, NADH, and ATP were ineffective. Reaction of rabbit anti-citrate synthase with citrate synthase and its proteolytic fragments indicated that the main antigenic region lay primarily in the small fragment. The products of subtilisin cleavage were isolated by gel filtration under denaturing conditions. The large (Mr 35 000-38 500) fragment contained the amino-terminal (approximately)336 amino acids and the small fragment contained the remaining carboxyl-terminal amino acids. The results are discussed in relation to the structure of citrate synthase.

Amino Acid Sequence↗
PubMedDate not supplied

Analysis of calcium, oxalate, and citrate interaction in idiopathic calcium urolithiasis in children.

The majority of urinary stones in children are composed of calcium oxalate. To investigate the interaction between urinary calcium, oxalate, and citrate as major risk factors for calcium stones formation, their 24-h urinary excretion was determined in 30 children with urolithiasis and 15 normal healthy children. The cutoff points between children with urolithiasis and healthy children, accuracy, sensitivity, and specificity for each risk factor alone as well as for all three taken together were determined. OneR and J4.8 classifiers as parts of the larger data mining software Weka, based on machine learning algorithms, were used for the determination of the cutoff points for differentiation of the children. The decision tree based on J4.8 classifier analysis of all three risk factors together proved to be the best for differentiating stone formers from normal children. In comparison to the accuracy of the differentiation after calcium and oxalate of 80% and 75.6%, respectively, the decision tree showed an accuracy of 97.8%. Even when its stability was tested by the leave-one-out cross-validation procedure, the accuracy remained at a very acceptable percentage of 93.2% correctly classified patients. J4.8 classifier analysis gave a look inside urinary calcium, oxalate, and citrate interaction. Urinary calcium excretion was shown as the most informative in discrimination of the children with urolithiasis from healthy children. However, it was shown that oxalate and citrate excretions might influence the stone formation in a subpopulation of the stone formers. In patients with low urinary calcium, a major role in lithogenesis belongs to oxalate, in some of them alone and in others in conjunction with citrate. Decreased urinary citrate excretion in the presence of increased oxalate excretion may lead to stone formation.

Adolescent↗
PubMed2005

Dimeric dioxomolybdenum(VI) and oxomolybdenum(V) complexes with citrate at very low pH and neutral conditions.

A novel dimeric dioxomolybdenum(VI) citrate complex, K[(MoO2)2-(OH)(H2cit)2].4H2O (1), with weak coordination of beta-carboxylic acid groups and the first structural example of an oxomolybdenum(V) citrate complex, (NH4)6[Mo2O4(cit)2].3H2O (2) (H4cit = citric acid), are isolated in a very acidic solution (pH 0.5-1.0) and neutral conditions (pH 7.0-8.0), respectively. Complex 1 displays strong double hydrogen bonds through beta-carboxyl and beta-carboxylic acid groups [2.621(9) A]. Transformations of the dimeric molybdenum(VI) citrate show that protonation of a carboxyl group will weaken the coordination of molybdenum(VI) citrate. There are obvious dissociations of molybdenum(VI/V) citrate complexes based on 13C NMR observations in solution.

Citrates↗
PubMed1986

A urinary calcium-citrate index for the evaluation of nephrolithiasis.

We have performed a multivariate analysis of urine abnormalities in patients with calcium oxalate nephrolithiasis, in which effects of gender were also considered. The characteristic of patients that most clearly sets them apart from normal people is a high level of urine calcium for any given level of urine citrate. Other urine measurements cannot improve upon the separation between patients and normals provided by urine calcium and citrate, and their abnormal relationship to each other. Normal women have higher urine citrate and lower urine calcium than normal men or patients of either sex; normal men differ from stone forming men only moderately. Direct measurements of supersaturation are not helpful in distinguishing between patients and normals, once calcium and citrate have been considered. From our analysis, we have derived a new index for evaluating the significance of urine calcium and citrate levels that seems to offer a better basis for clinical diagnosis than criteria presently in use.

Calcium↗
PubMed1988

Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF.

Calcium citrate was evaluated as a dietary phosphate binder in 81 patients with end-stage renal disease. These patients were grouped as follows: Group 1, 43 patients who were treated with calcium citrate; and Group 2 (the control group), 38 patients who were treated with aluminum-containing compounds. Blood chemistries were measured monthly and medications adjusted to maintain the following levels: serum calcium, greater than 9 mg/dl; serum phosphorus, less than 5.5 mg/dl; and total CO2 content, greater than 22 mmol/liter. At the end of the treatment period, the following serum values were obtained in Groups 1 and 2, respectively: calcium, 9.6 +/- 1.2 mg/dl (mean +/- SD) versus 8.9 +/- 0.8 mg/dl (P less than 0.001); phosphorus 5.5 +/- 1.9 mg/dl versus 7.0 +/- 2.3 mg/dl (P less than 0.005); and calcium-phosphate product, 52 +/- 18 versus 61 +/- 21 (P less than 0.05). Differences in alkaline phosphatase, total CO2 content, and C-terminal parathyroid hormone (C-PTH) values were not statistically significant between the two groups. Fifteen patients in Group 1 were then switched to aluminum-containing compounds and chemistries were compared one month later. During calcium citrate therapy, serum calcium was significantly higher, while C-PTH and serum alkaline phosphatase were significantly reduced. No difference was noted in serum phosphorous and total CO2 content. A questionnaire completed by 17 patients in Group 1 documented excellent patient tolerance to calcium citrate. Hypercalcemia (greater than 10.5 mg/dl) was the only significant complication, but only one patient became symptomatic. We conclude that, as a phosphate binder, calcium citrate is at least as effective as aluminum-containing compounds.

Adult↗
PubMed1990

Citrate excretion in spinal cord patients.

Low urinary citrate is a risk factor in calcium renal stone disease. The aim of this work was to identify the factors responsible for the low excretion of citrate frequently observed in patients with spinal cord lesions. Thirty male patients with spinal cord lesions were studied by blood and urine biochemistry. The most important single factor related to urinary citrate was urinary potassium. The presence or absence of urinary stone disease and variations in urinary volume also contributed significantly to variations in citrate excretion. Determination of plasma and urinary citrate, urinary sodium and bacteriological culture of urine permitted complete discrimination of the 7 stone formers from the other patients.

Citrates↗
PubMed2002

Slow component of [V]O(2) kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity.

OBJECTIVE: In healthy individuals performing constant-load exercise at intensities above the lactate threshold a secondary rise in pulmonary oxygen uptake ([V]O(2)) occurs. [V]O(2) reaches a maximum and exhaustion rapidly prevails for a range of work rates lower than the maximal work rate achieved during a conventional rapid-incremental test. This phenomenon is called the slow component (SC) of [V]O(2) kinetics and represents an increase in [V]O(2) without an increase in work rate. Although still under debate, the magnitude of the SC is believed to be associated with the percentage of type II muscle fibres and their recruitment. In this study we investigated the relationship between the magnitude of the relative SC, citrate synthase activity, UCP2 and UCP3 mRNA levels and muscle fibre composition in both endurance-trained and recreationally active subjects. METHOD: The magnitude of the relative SC was measured in 12 endurance-trained (Tr) and 15 recreationally active (RA) male subjects. The magnitude of the relative SC was determined as the difference between the end-exercise [V]O(2) and 3 min [V]O(2) divided by the difference between end-exercise [V]O(2) and baseline [V]O(2). UCP2 and UCP3 mRNA expression in the vastus lateralis was measured by RT-PCR with beta-actin mRNA used as an internal control. These values were also normalized against cytochrome-b mRNA to control for training induced changes in mitochondria when comparing the Tr and RA groups. Type I, IIa and IIx skeletal muscle fibre composition was determined using a routine myosin ATPase histochemical staining technique. Citrate synthase (CS) activity was measured using spectrophotometric detection. RESULTS: The magnitude of the relative SC of the Tr group had the highest correlation with citrate synthase activity (r=-0.90, P<0.001) and that of the RA group with [V]O(2) peak (r=-0.68, P<0.01). For the Tr group other correlations with the magnitude of the relative SC included UCP3 mRNA levels (r=0.69, P<0.05) and the percentage of type I fibres (r=-0.58, P<0.05), while for the RA group they included UCP3 mRNA (r=0.58, P<0.05) and the percentage of type IIa muscle fibres (r=0.59, P<0.05). The Tr subjects had a lower relative SC (P=0.04) and a lower expression of UCP2 (P=0.04), and UCP3 mRNA (P=0.01) than the RA subjects. When the groups were combined the magnitude of the relative SC correlated with UCP3 mRNA (r=0.70, P<0.01), percentage of type IIa muscle fibres (r=0.60, P<0.01) and [V]O(2) peak (r=-0.73, P<0.01). Additionally UCP3 mRNA correlated with the percentage of type IIa muscle fibres (r=0.63, P<0.001). CONCLUSION: Citrate synthase activity and [V]O(2) peak are indicators of aerobic fitness. The high negative correlations between the magnitude of the relative SC and citrate synthase activity and [V]O(2) peak, of the Tr and RA subjects, respectively, suggests that the magnitude of the relative SC is inversely correlated with aerobic fitness. Additionally the correlations between UCP3 mRNA and the magnitude of the relative SC for both groups individually and combined suggest that the uncoupling activity of the UCP3 protein may also influence the magnitude of the relative SC.

Adult↗