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)

The catabolic pathway of N-acetylglucosamine (GlcNAc) in Candida albicans is an important facet of its pathogenicity. One of the pathway genes, encoding glucosamine-6-phosphate deaminase (NAG1) is transcriptionally regulated by GlcNAc. Sequence analysis of a 4-kb genomic clone containing NAG1 indicates that this gene is part of a cluster containing two other genes of the GlcNAc catabolic pathway, i.e., DAC1, GlcNAc-6-phosphate deacetylase, and HXK1, hexokinase. All three genes are temporally and coordinately induced by GlcNAc suggesting a common regulatory mechanism for these genes. The NAG1 promoter is up-regulated when induced by GlcNAc in C. albicans but not in Saccharomyces cerevisiae. In vivo analysis of the deletion constructs delineated the minimal promoter to -130 bp and mapped two regions at -200 and -400 bp upstream of +1 (ATG) responsible for GlcNAc induction. Gel mobility-shift assays and "footprinting" (DNase protection method) analyses revealed two regions, 5'-GGAGCAAAAAAATGT 3' (-164 to -150, box A) and 5'-ACGGTGAGTTG 3' (-291 to -281, box B), that are recognized and bound by at least two inducible activator proteins directing the regulation of gene expression.
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PMID:The inducible N-acetylglucosamine catabolic pathway gene cluster in Candida albicans: discrete N-acetylglucosamine-inducible factors interact at the promoter of NAG1. 1111 81

Melanoma exhibits heterogeneous growth patterns and widely varying sensitivities to multiple treatment modalities. This variability may reflect intrinsic genetic differences in factors giving rise to altered metabolism. Glucose is the primary energy source of tumours, including melanoma, and glucose transporter isoform 1 (Glut-1) and hexokinase are key rate-limiting factors in glucose metabolism. The levels of Glut-1 and total hexokinase activity were measured in 31 melanoma biopsies to determine the extent of tumour-to-tumour variability in these parameters. Relative Glut-1 levels were determined by Western immunoblot analysis using human anti-Glut-1 rabbit polyclonal antibody, and hexokinase activity was measured in the same samples by an enzymatic assay monitoring the reduction in the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) (in nmol NADP+ reduced/min per mg protein). All melanomas were from patients who had received no therapy prior to surgery. Immediately after excision, tumour biopsies were disaggregated to single cells by collagenase and DNase and frozen in liquid nitrogen. Thirty human melanomas exhibited a 22-fold variation in levels of Glut-1 and 29 exhibited a nine-fold variation in total cellular hexokinase activity. Glut-1 levels and hexokinase activity were not correlated with one another. The broad range in Glut-1 levels and hexokinase activity observed between melanomas suggests that these glycolytic rate-limiting parameters that influence the rate of glucose metabolism may contribute to the variability in melanoma response to treatment modalities.
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PMID:Variability in glucose transporter-1 levels and hexokinase activity in human melanoma. 1182 56