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

Twenty Entamoeba histolytica strains from patients with HIV-1 infection were isolated and compared with E. histolytica strains from patients without HIV infection. The isoenzyme pattern of the hexokinase as well as the hybridization with known DNA-probes were used as markers for pathogenicity. According to these markers, all 20 strains could be regarded as being nonpathogenic. Direct measurements of the virulence were carried out: destruction of monolayer tissue culture cells, capacity of phagocytosis and the ability to induce liver abscesses in the hamster. The virulence of strains from HIV patients was comparable to that of E. histolytica strains which had been isolated from HIV-negative asymptomatic carriers. In agreement with this, none of the HIV-positive patients showed symptoms of an invasive amebiasis. By PRC, no HIV-1 proviral DNA could be evidenced in the E. histolytica strains which had been isolated from HIV patients.
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PMID:Characterization of 20 Entamoeba histolytica strains isolated from patients with HIV infection. 188 71

Using 3D searching techniques based on algorithms derived from graph theory, we have established two previously unreported structural similarities involving the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT). First, we report that there is a strong similarity between the 3D folds of the RNase H domain of RT and the 'ATPase folds' of hexokinase, the 70 kDa heat-shock cognate protein and actin. Like RNase H, these enzymes are involved in nucleotide binding and metal ion-catalysed cleavage of a phosphodiester bond. Similarities of the folding motif and the position of the metal-binding site in these enzymes suggest possible functional analogies and evolutionary relationships with RNase H. Second, we find there is a strong resemblance between the folds of the RNase H domain and of the p66 and p51 'connection' domains of RT. It is possible that this striking similarity within the RT structure indicates a possible ancestral gene doubling event. The similarity may also indicate that the connection domains possess functional roles in addition to those previously suggested, and they may therefore represent a further target for the design of therapeutic agents.
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PMID:Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques. 768 87

Human immunodeficiency virus type 1 encoded viral protein Vpr is essential for infection of macrophages by HIV-1. Furthermore, these macrophages are resistant to cell death and are viral reservoir. However, the impact of Vpr on the macrophage proteome is yet to be comprehended. The goal of the present study was to use a stable-isotope labeling by amino acids in cell culture (SILAC) coupled with mass spectrometry-based proteomics approach to characterize the Vpr response in macrophages. Cultured human monocytic cells, U937, were differentiated into macrophages and transduced with adenovirus construct harboring the Vpr gene. More than 600 proteins were quantified in SILAC coupled with LC-MS/MS approach, among which 136 were significantly altered upon Vpr overexpression in macrophages. Quantified proteins were selected and clustered by biological functions, pathway and network analysis using Ingenuity computational pathway analysis. The proteomic data illustrating increase in abundance of enzymes in the glycolytic pathway (pentose phosphate and pyruvate metabolism) was further validated by western blot analysis. In addition, the proteomic data demonstrate down regulation of some key mitochondrial enzymes such as glutamate dehydrogenase 2 (GLUD2), adenylate kinase 2 (AK2) and transketolase (TKT). Based on these observations we postulate that HIV-1 hijacks the macrophage glucose metabolism pathway via the Vpr-hypoxia inducible factor 1 alpha (HIF-1 alpha) axis to induce expression of hexokinase (HK), glucose-6-phosphate dehyrogenase (G6PD) and pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and biogenesis, and long-term survival of macrophages. Furthermore, dysregulation of mitochondrial glutamate metabolism in macrophages can contribute to neurodegeneration via neuroexcitotoxic mechanisms in the context of NeuroAIDS.
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PMID:HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative analysis. 2387 3

Viruses have developed various strategies to protect infected cells from apoptosis. HIV-1 infected macrophages are long-lived and considered reservoirs for HIV-1. One significant deciding factor between cell survival and cell death is glucose metabolism. We hypothesized that HIV-1 protects infected macrophages from apoptosis in part by modulating the host glycolytic pathway specifically by regulating hexokinase-1 (HK-1) an enzyme that converts glucose to glucose-6-phosphate. Therefore, we analyzed the regulation of HK-1 in HIV-1 infected PBMCs, and in a chronically HIV-1 infected monocyte-like cell line, U1. Our results demonstrate that HIV-1 induces a robust increase in HK-1 expression. Surprisingly, hexokinase enzymatic activity was significantly inhibited in HIV-1 infected PBMCs and in PMA differentiated U1 cells. Interestingly, we observed increased levels of mitochondria-bound HK-1 in PMA induced U1 cells and in the HIV-1 accessory protein, viral protein R (Vpr) transduced U937 cell derived macrophages. Dissociation of HK-1 from mitochondria in U1 cells using a pharmacological agent, clotrimazole (CTZ) induced mitochondrial membrane depolarization and caspase-3/7 mediated apoptosis. Dissociation of HK-1 from mitochondria in Vpr transduced U937 also activated caspase-3/7 activity. These observations indicate that HK-1 plays a non-metabolic role in HIV-1 infected macrophages by binding to mitochondria thereby maintaining mitochondrial integrity. These results suggest that targeting the interaction of HK-1 with the mitochondria to induce apoptosis in persistently infected macrophages may prove beneficial in purging the macrophage HIV reservoir.
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PMID:Role of hexokinase-1 in the survival of HIV-1-infected macrophages. 2560 55

Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1. HIV-1 infected CD4+ T cells showed a marked increase in expression of HK1, as well as the functionally related voltage-dependent anion channel (VDAC) protein, but not HK2. The elevation of GLUT, HK1, and VDAC expression in HIV-1 infected cells mirrored replication kinetics and was dependent on virus replication, as evidenced by the use of reverse transcription inhibitors. Finally, we demonstrated that the upregulation of HK1 in HIV-1 infected CD4+ T cells is independent of the viral accessory proteins Vpu, Vif, Nef, and Vpr. Though these data are consistent with HIV-1 dependency on CD4+ T cell glucose metabolism, a cellular response mechanism to infection cannot be ruled out.
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PMID:Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1. 2951 29