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09:43
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
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Metformin Affects Heme Function as a Possible Mechanism of Action
Xiyan Li1, Xin Wang1, Michael P Snyder2
1Department of Genetics, Stanford University, Stanford, CA 94305-5120.
G3 (Bethesda, Md.)
|December 17, 2018
Summary
Metformin, a diabetes drug, may work by regulating heme, a molecule crucial for cellular metabolism. This study shows metformin impacts heme production and redox states in key proteins.
Area of Science:
- Biochemistry
- Cellular Metabolism
- Pharmacology
Background:
- Metformin is a widely used drug for diabetes with potential benefits in cancer and aging.
- The precise mechanism of metformin's action remains incompletely understood.
- Heme and hemoproteins play critical roles in various cellular processes.
Purpose of the Study:
- To investigate the role of heme and hemoproteins in metformin's mechanism of action.
- To explore how metformin affects heme synthesis and redox states.
Main Methods:
- Assessing heme production in yeast, human erythrocytes, erythropoietic cells, and hepatocytes.
- Evaluating metformin's effect on heme oxidation in protein scaffolds like cytochrome c, myoglobin, and hemoglobin.
- Determining binding affinities (Kd values) for metformin-heme interactions.
Main Results:
- Metformin suppressed heme production by 50% in yeast and 30-50% in human cells.
- Mitochondrial function was necessary for metformin's suppression of heme synthesis.
- Metformin prevented heme oxidation in cytochrome c, myoglobin, and hemoglobin with low Kd values (< 3 mM).
Conclusions:
- Metformin's action may involve the regulation of heme metabolism and redox states.
- The drug appears to stabilize redox transitions in heme and other porphyrin-containing groups.
- This heme-centric mechanism could explain metformin's pleiotropic effects on cellular metabolism.
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