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Biochemistry. Biokhimiia Sep 2008Data on the structure, functions, regulation of activity, and expression of cytosolic and mitochondrial aconitate hydratase isoenzymes of mammals are reviewed. The role... (Review)
Review
Data on the structure, functions, regulation of activity, and expression of cytosolic and mitochondrial aconitate hydratase isoenzymes of mammals are reviewed. The role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron is described. Information on modifications of the aconitate hydratase molecule and changes in expression under oxidative stress is generalized. The role of aconitate hydratase in the pathogenesis of some diseases is considered.
Topics: Aconitate Hydratase; Animals; Citrates; Cytoplasm; Humans; Iron; Isocitrates; Mammals; Mitochondria; Oxidative Stress
PubMed: 18976211
DOI: 10.1134/s0006297908090010 -
BMC Plant Biology Oct 2010Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main...
BACKGROUND
Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main determinants of taste and organoleptic quality of fruits and hence the control of fruit acidity loss has a strong economical relevance. In citrus, organic acids accumulate in the juice sac cells of developing fruits and are catabolized thereafter during ripening. Aconitase, that transforms citrate to isocitrate, is the first step of citric acid catabolism and a major component of the citrate utilization machinery. In this work, the citrus aconitase gene family was first characterized and a phylogenetic analysis was then carried out in order to understand the evolutionary history of this family in plants. Gene expression analyses of the citrus aconitase family were subsequently performed in several acidic and acidless genotypes to elucidate their involvement in acid homeostasis.
RESULTS
Analysis of 460,000 citrus ESTs, followed by sequencing of complete cDNA clones, identified in citrus 3 transcription units coding for putatively active aconitate hydratase proteins, named as CcAco1, CcAco2 and CcAco3. A phylogenetic study carried on the Aco family in 14 plant species, shows the presence of 5 Aco subfamilies, and that the ancestor of monocot and dicot species shared at least one Aco gene. Real-time RT-PCR expression analyses of the three aconitase citrus genes were performed in pulp tissues along fruit development in acidic and acidless citrus varieties such as mandarins, oranges and lemons. While CcAco3 expression was always low, CcAco1 and CcAco2 genes were generally induced during the rapid phase of fruit growth along with the maximum in acidity and the beginning of the acid reduction. Two exceptions to this general pattern were found: 1) Clemenules mandarin failed inducing CcAco2 although acid levels were rapidly reduced; and 2) the acidless "Sucreña" orange showed unusually high levels of expression of both aconitases, an observation correlating with the acidless phenotype. However, in the acidless "Dulce" lemon aconitase expression was normal suggesting that the acidless trait in this variety is not dependent upon aconitases.
CONCLUSIONS
Phylogenetic studies showed the occurrence of five different subfamilies of aconitate hydratase in plants and sequence analyses identified three active genes in citrus. The pattern of expression of two of these genes, CcAco1 and CcAco2, was normally associated with the timing of acid content reduction in most genotypes. Two exceptions to this general observation suggest the occurrence of additional regulatory steps of citrate homeostasis in citrus.
Topics: Aconitate Hydratase; Amino Acid Sequence; Carboxylic Acids; Citric Acid; Citrus; Cloning, Molecular; DNA, Complementary; Expressed Sequence Tags; Fruit; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Humans; Hydrogen-Ion Concentration; Isoenzymes; Molecular Sequence Data; Multigene Family; Phylogeny; Plant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Sequence Homology, Amino Acid
PubMed: 20958971
DOI: 10.1186/1471-2229-10-222 -
Biochimie Mar 2020We propose a new model for prochirality that satisfies all known examples: the prochiral plane. This plane contains the prochiral carbon and defines two separate faces...
We propose a new model for prochirality that satisfies all known examples: the prochiral plane. This plane contains the prochiral carbon and defines two separate faces for chemical modification. We extend this to enzyme catalysis, replacing the "three point attachment" hypothesis and its variants. Once a prochiral substrate is fixed on an enzyme surface, the asymmetry of the enzyme provides reactants exclusively on one side of the prochiral plane, producing an enantiomerically pure chiral product. The aconitase reaction is detailed as an example, using molecular modeling and its known enzymatic mechanism. We show that the prochiral substrate for this enzyme is not citrate, but rather cis-aconitate. The number of interaction points of cis-aconitate is not relevant to prochirality, but rather to substrate specificity. A second detailed example is the enzyme fumarase; here the substrate fumarate has only two binding sites, but is nonetheless fixed onto the enzyme and has a defined prochiral plane. We also provide a literature survey of more prochiral substrates, all of which have sp hybridized carbon and contain a prochiral plane. An example of a prochiral unnatural substrate for sphingosine kinase 2, fingolimod, has an sp hybridized prochiral carbon and also contains a prochiral plane. Finally, we provide an intuitive example of a prochiral physical object, a coffee cup, interacting with one hand and lip.
Topics: Aconitate Hydratase; Aconitic Acid; Binding Sites; Catalysis; Citrates; Fumarate Hydratase; Models, Molecular; Mycobacterium tuberculosis; Stereoisomerism; Substrate Specificity
PubMed: 31862235
DOI: 10.1016/j.biochi.2019.12.009 -
Biochemistry and Cell Biology =... Jul 1988This paper describes the characterization of aconitate hydratase (EC 4.2.1.3) in cytoplasmic and mitochondrial extracts from Ehrlich ascites tumor cells carried by... (Comparative Study)
Comparative Study
This paper describes the characterization of aconitate hydratase (EC 4.2.1.3) in cytoplasmic and mitochondrial extracts from Ehrlich ascites tumor cells carried by BALB/C mice. The results show a similar distribution of aconitate hydratase in both extracts, with specific activities much lower than those found in pig and mouse tissues. Mitochondrial aconitate hydratase shows a substrate inhibition by citrate with a Km similar to that found in cytoplasm (Km = 1.0 mM and 0.9 mM, respectively). Oxalacetate produces a mixed type of inhibition in both cytoplasmic and mitochondrial aconitate hydratases with different inhibition constants (Ki = 0.3 mM and 1.0 mM, respectively). Moreover, the specific activities of aconitate hydratase in both cytoplasm and mitochondria decrease when the tumor progresses in the peritoneum of BALB/C mice, as well as the percentage of aconitate hydratase activity in the presence of oxalacetate as the inhibitor. These results indicate that the activity and kinetics of aconitate hydratase are markedly altered by neoplastic transformation as occurs in Ehrlich ascites tumor cells. Since aconitate hydratase is not a key enzyme, these unexpected data are of interest in the study of cancer biochemistry.
Topics: Aconitate Hydratase; Animals; Carcinoma, Ehrlich Tumor; Cytoplasm; Male; Mice; Mice, Inbred BALB C; Mitochondria; Tumor Cells, Cultured
PubMed: 3179020
DOI: 10.1139/o88-090 -
Transactions of the Royal Society of... 1991
Topics: Aconitate Hydratase; Animals; Electrophoresis, Starch Gel; Leishmania; Trypanosomatina
PubMed: 1780985
DOI: 10.1016/0035-9203(91)90358-6 -
International Journal of Molecular... Apr 2023This paper presents an analysis of the regulation activity of the partially purified preparations of cellular aconitate hydratase (AH) on the yeast cultivated at...
This paper presents an analysis of the regulation activity of the partially purified preparations of cellular aconitate hydratase (AH) on the yeast cultivated at extreme pH. As a result of purification, enzyme preparations were obtained from cells grown on media at pH 4.0, 5.5, and 9.0, purified by 48-, 46-, and 51-fold and having a specific activity of 0.43, 0.55 and 0.36 E/mg protein, respectively. The kinetic parameters of preparations from cells cultured at extreme pH demonstrated: (1) an increase in the affinity for citrate and isocitrate; and (2) a shift in the pH optima to the acidic and alkaline side in accordance with the modulation of the medium pH. The regulatory properties of the enzyme from cells subjected to alkaline stress showed increased sensitivity to Fe ions and high peroxide resistance. Reduced glutathione (GSH) stimulated AH, while oxidized glutathione (GSSG) inhibited AH. A more pronounced effect of both GSH and GSSG was noted for the enzyme obtained from cells grown at pH 5.5. The data obtained provide new approaches to the use of as a model of eukaryotic cells demonstrating the development of a stress-induced pathology and to conducting a detailed analysis of enzymatic activity for its correction.
Topics: Aconitate Hydratase; Yarrowia; Oxidation-Reduction; Hydrogen-Ion Concentration
PubMed: 37108831
DOI: 10.3390/ijms24087670 -
The American Journal of the Medical... Sep 2019
Topics: Aconitate Hydratase; Goals; Humans; Lactic Acid; Resuscitation; Sepsis; Shock, Septic
PubMed: 31300149
DOI: 10.1016/j.amjms.2019.05.010 -
The Biochemical Journal Oct 1962
Topics: Aconitate Hydratase; Citrates; Mixed Function Oxygenases; Plants
PubMed: 13994045
DOI: 10.1042/bj0850113 -
Nature Reviews. Molecular Cell Biology Dec 2001
Topics: Aconitate Hydratase; Chaperonin 10; Chaperonin 60; Protein Folding; Ribulose-Bisphosphate Carboxylase; Substrate Specificity; Thiosulfate Sulfurtransferase
PubMed: 11733765
DOI: 10.1038/35103054 -
Advanced Biology Jul 2023Certain metabolic interventions such as caloric restriction, fasting, exercise, and a ketogenic diet extend lifespan and/or health span. However, their benefits are... (Review)
Review
Certain metabolic interventions such as caloric restriction, fasting, exercise, and a ketogenic diet extend lifespan and/or health span. However, their benefits are limited and their connections to the underlying mechanisms of aging are not fully clear. Here, these connections are explored in terms of the tricarboxylic acid (TCA) cycle (Krebs cycle, citric acid cycle) to suggest reasons for the loss of effectiveness and ways of overcoming it. Specifically, the metabolic interventions deplete acetate and likely reduce the conversion of oxaloacetate to aspartate, thereby inhibiting the mammalian target of rapamycin (mTOR) and upregulating autophagy. Synthesis of glutathione may provide a high-capacity sink for amine groups, facilitating autophagy, and prevent buildup of alpha-ketoglutarate, supporting stem cell maintenance. Metabolic interventions also prevent the accumulation of succinate, thereby slowing DNA hypermethylation, facilitating the repair of DNA double-strand breaks, reducing inflammatory and hypoxic signaling, and lowering reliance on glycolysis. In part through these mechanisms, metabolic interventions may decelerate aging, extending lifespan. Conversely, with overnutrition or oxidative stress, these processes function in reverse, accelerating aging and impairing longevity. Progressive damage to aconitase, inhibition of succinate dehydrogenase, and downregulation of hypoxia-inducible factor-1α, and phosphoenolpyruvate carboxykinase (PEPCK) emerge as potentially modifiable reasons for the loss of effectiveness of metabolic interventions.
Topics: Citric Acid Cycle; Aconitate Hydratase; Glycolysis; DNA
PubMed: 37132059
DOI: 10.1002/adbi.202300095