ArticleThe Journal of biological chemistry2011
Glycerol 3-phosphate alters Trypanosoma brucei hexokinase activity in response to environmental change.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Measuring Dynamic Glycosomal pH Changes in Living Trypanosoma brucei.Journal of visualized experiments : JoVE · 2024Article
- Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.PLoS biology · 2021Article
- Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions.PLoS pathogens · 2018Article
- A targeted delivery strategy for the development of potent trypanocides.Chemical communications (Cambridge, England) · 2017Article
- pH regulation in glycosomes of procyclic formThe Journal of biological chemistry · 2017Article
- Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension.Aging · 2016Article
- A unique hexokinase in Cryptosporidium parvum, an apicomplexan pathogen lacking the Krebs cycle and oxidative phosphorylation.Protist · 2014Article
- Interrogating a hexokinase-selected small-molecule library for inhibitors of Plasmodium falciparum hexokinase.Antimicrobial agents and chemotherapy · 2013Article
- Environmentally regulated glycosome protein composition in the African trypanosome.Eukaryotic cell · 2013Article
- Peptide-targeted delivery of a pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei.Biochemistry · 2013Article
- Pexophagy: the selective degradation of peroxisomes.International journal of cell biology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The African trypanosome, Trypanosoma brucei, compartmentalizes some metabolic enzymes within peroxisome-like organelles called glycosomes. The amounts, activities, and types of glycosomal enzymes are modulated coincident with developmental and environmental changes. Pexophagy (fusion of glycosomes with acidic lysosomes) has been proposed to facilitate this glycosome remodeling. Here, we report that, although glycosome-resident enzyme T. brucei hexokinase 1 (TbHK1) protein levels are maintained during pexophagy, acidification inactivates the activity. Glycerol 3-phosphate, which is produced in vivo by a glycosome-resident glycerol kinase, mitigated acid inactivation of lysate-derived TbHK activity. Using recombinant TbHK1, we found that glycerol 3-P influenced enzyme activity at pH 6.5 by preventing substrate and product inhibition by ATP and ADP, respectively. Additionally, TbHK1 inhibition by the flavonol quercetin (QCN) was partially reversed by glycerol 3-P at pH 7.4, whereas at pH 6.5, enzyme activity in the presence of QCN was completely maintained by glycerol 3-P. However, glycerol 3-P did not alter the interaction of QCN with TbHK1, as the lone Trp residue (Trp-177) was quenched under all conditions tested. These findings suggest potential novel mechanisms for the regulation of TbHK1, particularly given the acidification of glycosomes that can be induced under a variety of parasite growth conditions.
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