Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the rate-limiting heme biosynthetic enzyme 5'-aminolevulinate synthase (ALAS) was investigated in skeletal muscle of 3-wk-old rats fed an iron-deficient diet. After 14 days, ALAS activity had declined 70% relative to control (2.1 +/- 0.2 vs. 0.6 +/- 0.1 nmol.h-1.g-1; P less than 0.005). Similar decreases were observed for blood hemoglobin (11.4 +/- 0.2 vs. 3.9 +/- 0.3 g/dl; P less than 0.005) and muscle cytochrome c (14.5 +/- 1.3 vs. 7.1 +/- 0.6 nmol/g; P less than 0.005). An iron-deficient diet decreased body and skeletal muscle growth by 15 (P less than 0.005) and 10% (P less than 0.05), respectively, whereas concentrations of protein, RNA, ALAS mRNA, and citrate synthase activity in muscle were not different from control. One mechanism by which heme biosynthesis may be slowed in muscle of young anemic rats is a decrease in ALAS activity. At a time when enzyme activity was decreased, ALAS mRNA expression was not affected by an iron-deficient diet, suggesting that steps after transcription of the ALAS gene may regulate the decrease in activity.
 ...
PMID:5'-Aminolevulinate synthase activity is decreased in skeletal muscle of anemic rats. 132 16

In order to examine the effects of mild iron deficiency on physical work capacity, 40 prelatent iron-deficient female endurance runners were studied before and after 8 wk of supplementation with either oral iron (320 mg ferrous sulfate) or a matching placebo. Subjects underwent the following physical work capacity tests: the Wingate cycle ergometer test, the anaerobic speed test, the ventilatory threshold, VO2max, and maximal treadmill velocity during the VO2max test. Muscle biopsy samples pre- and post-treatment were obtained from 17 of the subjects, and these were assayed for citrate synthase and cytoplasmic alpha-glycerophosphate dehydrogenase activity. Subjects were randomly assigned to one of the treatment groups, and a double-blind method of administration of the supplements was used. The differences in improvement scores between the two groups on the work capacity and enzyme activity variables were statistically nonsignificant (P greater than 0.05). Serum ferritin values rose from a mean of 12.4 +/- 4.5 to 37.7 +/- 19.7 ng.ml-1 for the experimental group and from 12.2 +/- 4.3 to 17.2 +/- 8.9 ng.ml-1 for the controls (P = 0.0025), whereas hemoglobin levels remained fairly constant for both groups (P = 0.6). Eight weeks of iron supplementation to prelatent/latent iron-deficient, physically active females did not significantly enhance work capacity. Within the limitations of this study, the presence of a serum ferritin below 20 ng.ml-1 does not pose a significant handicap to physical work capacity.
 ...
PMID:The effects of prelatent/latent iron deficiency on physical work capacity. 273 74

The purpose of this study was to determine whether severe iron deficiency alters the adaptive response of skeletal muscle fibers to a sustained increase in tonic contractile activity. Seven weanling rabbits consumed a low iron diet and underwent phlebotomy twice weekly for 6 mo, resulting in severe anemia (mean Hb 5.5 g/dl). Compared with control animals, tibialis anterior skeletal muscles of iron-deficient animals exhibited reduced concentrations of cytochrome c (4.4 +/- 0.7 vs. 8.6 +/- 0.7 nmol/g tissue; P less than 0.01), and reduced activities of citrate synthase (83 +/- 10 vs. 133 +/- 13 mU/mg protein; P less than 0.01) and cytochrome-c oxidase (2.2 +/- 0.2 vs. 3.6 +/- 0.5 U/mg protein; P less than 0.05). In these muscles mitochondria were swollen and displayed deformed cristae. Less severe biochemical abnormalities were observed in cardiac and soleus skeletal muscles. Ten days of continuous electrical stimulation of the motor nerve supplying anterior compartment muscles of iron-deficient rabbits increased expression of mitochondrial proteins: cytochrome c was increased to 154% of control levels (P less than 0.05), and cytochrome-c oxidase and citrate synthase activities were increased to 199 and 272% of control levels, respectively (P less than 0.005). In addition, electrical pacing increased the fractional volume of mitochondria observed by electron microscopy and reduced the activity of aldolase A by 28% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activity-induced adaptations in skeletal muscles of iron-deficient rabbits. 284 18

This paper presents a study of the metabolic and contractile types of 34 samples from 30 muscles in five crossbred Pietrain-Large White pigs 6 to 7 months old. The activity of the following enzymes was measured: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase using high (LDH-h) or low (LDH-b) pyruvate concentrations in the reaction medium, citrate synthase (CS), and myofibrillar Ca-Mg activated ATPase. Haeminic iron and ultimate pH (pHu) were measured on the same samples. The results showed a negative, rather linear relationship between GAPDH, LDH and ATPase activities on the one hand and CS and haeminic iron on the other. Rather high correlations (r = 0.7 to 0.8) were observed between metabolic and contractile criteria and pHu; the red (slow) muscles had the highest pHu.
 ...
PMID:[Enzyme metabolic and contractile activities of 30 pig muscles. Relation with the final ph attained after death]. 293 86

It has been reported that the mitochondrial cytochromes and citrate cycle enzymes occur in constant proportions to each other and increase or decrease roughly in parallel in response to various stimuli. The purpose of this study was to determine whether this proportionality is an obligatory consequence of the way in which mitochondria are assembled. Severe iron deficiency was used to bring about decreases of the iron-containing constituents of the mitochondrial respiratory chain in skeletal muscle. Cytochrome c concentration and cytochrome oxidase activity were decreased approximately 50%, while succinate dehydrogenase and NADH dehydrogenase activities were decreased by 78% in iron-deficient muscle. On electron microscopic examination, mitochondria in iron-deficient muscles had relatively sparse numbers of cristae. The iron deficiency had little or no effect on the levels of a range of mitochondrial matrix enzymes, including citrate synthase, isocitrate dehydrogenase, fumarase, aspartate aminotransferase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and acetoacetyl-CoA thiolase. These results show that the usual constant proportions between the constituents of the mitochondrial respiratory chain and matrix enzymes are not obligatory; they provide evidence that mitochondrial matrix enzymes and respiratory chain constituents can be incorporated into mitochondria independently and that the ratios between them can vary within wide limits.
 ...
PMID:Perturbation of mitochondrial composition in muscle by iron deficiency. Implications regarding regulation of mitochondrial assembly. 302 53

Young rats maintained on an iron-deficient diet developed severe anemia and had large decreases in the levels of the iron-containing flavoproteins and cytochromes of the mitochondrial respiratory chain in skeletal muscle. In contrast, the levels of a number of mitochondrial matrix marker enzymes, including citrate synthase, isocitrate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and aspartate aminotransferase, increased in red skeletal muscle but not in white muscle. Phosphocreatine concentration was decreased and inorganic phosphate concentration was increased in soleus muscle frozen in situ. We hypothesize that the increase in mitochondrial matrix enzymes reflects a stimulus to mitochondrial biogenesis in posture-maintaining and weight-bearing red muscle fibers in severely iron-deficient rats. It is our working hypothesis that this stimulus to mitochondrial biogenesis arises from mild activity of the red fibers and is due to the same perturbation in cellular homeostasis that is normally caused by vigorous exercise or hypoxia. In iron deficiency, the stimulus to mitochondrial biogenesis can induce an increase in only those enzymes not prevented from increasing by iron deficiency, resulting in formation of mitochondria of grossly abnormal composition.
 ...
PMID:Induction of an increase in mitochondrial matrix enzymes in muscle of iron-deficient rats. 347 8

Cells of the aerotolerant anaerobe Giardia lamblia respire in the presence of oxygen. Endogenous respiration is stimulated by glucose but not by other carbohydrates and Krebs cycle intermediates. Endogenous and glucose-stimulated respiration are insensitive to cyanide, malonate, and 2,4-dinitrophenol, but are inhibited by atabrin and iodoacetamide. G. lamblia produces ethanol, acetate and CO2 both aerobically and anaerobically either from endogenous reserves or exogenous glucose. Molecular hydrogen is not produced. The following enzyme activities were detected in homogenates: hexokinase, fructose-biphosphate aldolase, pyruvate kinase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, malate dehydrogenase (decarboxylating), pyruvate synthase, acetyl-CoA synthetase, alcohol dehydrogenase (NADP+), NADH dehydrogenase, NADPH dehydrogenase, NADPH oxidoreductase and superoxide dismutase. The enzymes of energy and carbohydrate metabolism are nonsedimentable (109 000 x g for 30 min). Activities of lactate dehydrogenase, hydrogenase, phosphate acetyltransferase, acetate kinase, citrate synthase, succinate dehydrogenase, fumarate hydratase and catalase were below the limits of detection. The results suggest the occurrence of glycolysis, energy production by substrate level phosphorylation and a flavin, iron-sulfur protein mediated electron transport system as well as the absence of cytochrome mediated oxidative phosphorylation and functional Krebs cycle.
 ...
PMID:Energy metabolism of the anaerobic protozoon Giardia lamblia. 610 7

The nucleotide sequence of a 3614 base-pair segment of DNA containing the sdhA gene, encoding the flavoprotein subunit of succinate dehydrogenase of Escherichia coli, and two genes sdhC and sdhD, encoding small hydrophobic subunits, has been determined. Together with the iron-sulphur protein gene (sdhB) these genes form an operon (sdhCDAB) situated between the citrate synthase gene (gltA) and the 2-oxoglutarate dehydrogenase complex genes (sucAB): gltA-sdhCDAB-sucAB. Transcription of the gltA and sdhCDAB gene appears to diverge from a single intergenic region that contains two pairs of potential promoter sequences and two putative CRP (cyclic AMP receptor protein)-binding sites. The sdhA structural gene comprises 1761 base-pairs (587 codons, excluding the initiation codon, AUG) and it encodes a polypeptide of Mr 64268 that is strikingly homologous with the flavoprotein subunit of fumarate reductase (frdA gene product). The FAD-binding region, including the histidine residue at the FAD-attachment site, has been identified by its homology with other flavoproteins and with the flavopeptide of the bovine heart mitochondrial succinate dehydrogenase. Potential active-site cysteine and histidine residues have also been indicated by the comparisons. The sdhC (384 base-pairs) and sdhD (342 base-pairs) structural genes encode two strongly hydrophobic proteins of Mr 14167 and 12792 respectively. These proteins resemble in size and composition, but not sequence, the membrane anchor proteins of fumarate reductase (the frdC and frdD gene products).
 ...
PMID:Nucleotide sequence encoding the flavoprotein and hydrophobic subunits of the succinate dehydrogenase of Escherichia coli. 638 59

The nucleotide sequence of a 961 base-pair segment of DNA containing the sdhB gene, which encodes the iron-sulphur protein subunit of the E. coli succinate dehydrogenase, has been determined. The sdhB structural gene comprises 711 base pairs (237 codons, excluding the translational initiator and terminator). It is separated by a 15 base-pair intergenic region from the preceding flavoprotein gene (sdhA) and is the distal gene of an operon that also includes genes (sdhC and D) encoding two hydrophobic subunits, sdhCDAB. The distal end of the sdh operon is linked to the 2-oxoglutarate dehydrogenase gene (sucA) by a complex region of dyad symmetry that is homologous with several potential intercistronic regulatory elements or transcriptional attenuators. The sdhB structural gene encodes a polypeptide of Mr26637 that is strikingly homologous with the iron-sulphur protein subunit of fumarate reductase (38% identity, increasing to 58% when conservative changes are included). Both subunits contain 11 cysteine residues, 10 being conserved in three clusters resembling those found in ferredoxins. This work completes the sequence of a 9897 base-pair segment of DNA containing seven tricarboxylic acid cycle genes encoding three enzymes or enzyme complexes, citrate synthase (gltA), succinate dehydrogenase (sdh), and the 2-oxoglutarate dehydrogenase complex (suc), that are organized thus: gltA-sdhCDAB-sucAB.
 ...
PMID:Nucleotide sequence encoding the iron-sulphur protein subunit of the succinate dehydrogenase of Escherichia coli. 638 71

The effects of chronic iron deficiency anemia on brain (cortex) metabolism were estimated by 31P-nuclear magnetic resonance spectroscopy and biochemical analyses in male Wistar rats. Iron deficiency anemia was induced by supplying diet containing either approximately 2 or approximately 6 ppm Fe. Control diet was supplemented with 100 ppm Fe as ferric citrate. After 8-9 weeks, blood hemoglobin levels were approximately 13, 5, and 3 g/100 ml in the 100 ppm, 6 ppm, and 2 ppm Fe group, respectively. The blood lactate levels at rest in these groups were approximately 3, 5, and 6 mM. The blood glucose concentration also tended to be elevated in iron-deficient rats. The high-energy phosphate contents in brain were not affected by iron deficiency. The activities of succinate dehydrogenase and cytochrome oxidase per unit protein in the 2 ppm Fe group were significantly less than in the 100 ppm Fe group, but those activities were not significantly affected by feeding diet with 6 ppm Fe. The activities of lactate dehydrogenase in iron-deficient group tended to be elevated but not significantly. The activities of non-iron containing mitochondrial enzymes, citrate synthase and beta-hydroxyacyl CoA dehydrogenase, were unchanged. It is suggested that the brain has a higher tolerance to iron deficiency than skeletal muscle in terms of the metabolic characteristics, although this may be associated with a lower level of neural activity.
 ...
PMID:Effects of chronic iron deficiency anemia on brain metabolism. 756 62


1 2 3 4 5 6 Next >>