Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mammalian brain tissue, most hexokinase is bound to the mitochondria and only a small amount of the enzyme is present in soluble form. In this study we report that, in rabbit brain, hexokinase is present in two distinct molecular forms, which we designated HKH and HKL, both of which are separable using hydrophobic interaction or anion-exchange chromatography. These two molecular forms can be detected when hexokinase is prepared at pH 7.4, whereas at pH 10.0 only the more hydrophobic form, HKH, is present. The two subtypes of hexokinase do not show significant differences in Km values for glucose and ATP, in Ki values for glucose-6-phosphate or in their molecular weights. HKH is able to rebind mitochondrial membranes, while HKL has lost this ability, suggesting that the hydrophobic peptide at the N-terminal has been removed. The susceptibility of the N-terminal peptide to proteolysis is completely inhibited by using antiproteolytic compounds, such as leupeptin or E-64. The results reported in this paper suggest that a cysteine protease, probably belonging to a the class of cathepsins, may be involved in the processing of bindable hexokinase to the non-bindable form in rabbit brain, and that the activity of this protease is pH-dependent.
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PMID:Rabbit brain hexokinase: evidence for the presence of two distinct molecular forms. 858 39

A critical review of the development of specific chemotherapeutic approaches for the management of American Trypanosomiasis or Chagas disease is presented, including controversies on the pathogenesis of the disease, the initial efforts that led to the development of currently available drugs (nifurtimox and benznidazole), limitations of these therapies and novel approaches for the development of anti-Trypanosoma cruzi drugs, based on our growing understanding of the biology of this parasite. Among the later, the most promising approaches are ergosterol biosynthesis inhibitors such as posaconazole and ravuconazole, poised to enter clinical trials for chronic Chagas disease in the short term; inhibitors of cruzipain, the main cysteine protease of T. cruzi, essential for its survival and proliferation in vitro and in vivo; bisphosphonates, metabolic stable pyrophosphate analogs that have trypanocidal activity through the inhibition of the parasite's farnesyl-pyrophosphate synthase or hexokinase; inhibitors of trypanothione synthesis and redox metabolism and inhibitors of hypoxanthine-guanine phosphoribosyl-transferase, an essential enzyme for purine salvage in T. cruzi and related organisms. Finally, the economic and political challenges faced by development of drugs for the treatment of neglected tropical diseases, which afflict almost exclusively poor populations in developing countries, are analyzed and recent potential solutions for this conundrum are discussed.
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PMID:Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. 1990 Mar 95

To gain an in-depth understanding of the role of ethylene in post harvest senescence, we used broccoli (Brassica oleracea var. italica) as our model species. The senescence-associated asparagine synthetase (AS) promoter from asparagus was used to drive the expression of an antisense 1-aminocyclopropane-1-carboxylate oxidase (ACO) cDNA from broccoli, BoACO2, to reduce ethylene production following harvest. Physiological analyses revealed that transgenic broccoli lines harbouring the antisense BoACO2 gene construct (designated as AS-asACO) displayed delayed senescence in both detached leaves and detached heads as measured by hue angle. Harvested floret tissue from these plants also showed a delayed loss of chlorophyll, lower protease activity and higher total protein content, and changes in transcript levels of senescence marker genes when compared with wild type and transgenic lines transformed with an empty T-DNA. Genes that were down-regulated included those coding for cysteine protease (BoCP5), metallothionein-like protein (BoMT1), hexokinase (BoHK1), invertase (BoINV1) and sucrose transporters (BoSUC1 and BoSUC2). Northern analysis for BoACO1 and BoACO2, ACO assays and western analysis, revealed reduced ACO transcript, enzyme activity and protein accumulation, as well as reduced ethylene production in the transgenic AS-asACO lines when compared with controls, confirming that a key enzyme regulating ethylene biosynthesis was reduced in these plants. This, together with the changes observed in gene expression, confirm a significant role for ethylene in regulating the events leading to senescence in broccoli following harvest.
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PMID:Senescence-associated down-regulation of 1-aminocyclopropane-1-carboxylate (ACC) oxidase delays harvest-induced senescence in broccoli. 3268 85