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Biphosphoglycerate Mutase: A Novel Therapeutic Target for Malaria?
Alessia Azzuolo1, Yunxiang Yang1, Albert Berghuis2
1Department of Biochemistry, Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada; Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.
Transfusion Medicine Reviews
|October 12, 2023
Summary
Biphosphoglycerate mutase (BPGM) deficiency protects mice against malaria by altering red blood cell metabolism. This suggests BPGM as a potential therapeutic target for malaria treatment.
Area of Science:
- Biochemistry
- Hematology
- Parasitology
Background:
- Biphosphoglycerate mutase (BPGM) produces 2,3-biphosphoglycerate (2,3-BPG), crucial for glycolysis and oxygen release.
- 2,3-BPG allosterically regulates hemoglobin (Hb), impacting oxygen delivery.
- BPGM deficiency in humans causes rare erythrocytic disorders.
Purpose of the Study:
- To investigate the role of BPGM deficiency in malaria pathogenesis.
- To explore BPGM as a potential therapeutic target for malaria.
Main Methods:
- Studied BPGM-deficient mice to model human deficiency.
- Assessed protection against malaria anemia and cerebral malaria in these mice.
Main Results:
- BPGM deficiency in mice protected against severe malaria anemia and cerebral malaria.
- These findings align with studies on other erythrocyte glycolytic enzymes like PKLR and G6PD.
Conclusions:
- BPGM deficiency confers significant protection against malaria in mice.
- BPGM and erythrocyte glycolysis represent novel therapeutic targets for malaria intervention.
