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Editorial
. 2021 Jan 1;106(1):9-11.
doi: 10.3324/haematol.2020.266585.

Targeting the red cell enzyme pyruvate kinase with a small allosteric molecule AG-348 may correct underlying pathology of a glycolytic enzymopathy

Abdu I Alayash  1
Affiliations
Editorial

Targeting the red cell enzyme pyruvate kinase with a small allosteric molecule AG-348 may correct underlying pathology of a glycolytic enzymopathy

Abdu I Alayash. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Schematic representation of the action of AG-348 on the enzyme pyruvate kinase in the final step of the glycolytic degradation of glucose in red blood cells (RBC). Glycolysis, the first step in cellular respiration begins with one glucose molecule (6 carbons) which is subsequently broken down in a series of enzymatic steps via ten enzymes into two pyruvic acid molecules (2 carbons) as well as releasing adenosine triphosphate and reduced nicotinamide adenine dinucleotide. The schemes on both sides (normal RBC metabolism and in pyruvate kinase deficiency) begin with the formation of 1,3 biphosphoglycerate after several enzymatic steps of phosphorylation and molecular arrangements. 2,3-bisphosphoglyceric acid (2,3-BPG), also known as 2,3-diphosphoglyceric acid (2,3-DPG) (allosteric affecter of hemoglobin), is a three-carbon isomer of the glycolytic intermediate 1,3-BPG. The final critical step in this reaction pathway involves the formation of pyruvate from phosphoenolpyruvate, a reaction catalyzed by the enzyme pyruvate kinase. The red cell in the center of the figure where these reactions occur is shown with two important receptors, Glut 1 and band 3, which play key roles in glucose transport and metabolism. The small molecule AG-348 penetrates the red cell and activates the enzyme pyruvate kinase.
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Comment on

References

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