If metabolism were an unregulated engine it would overheat in times of plenty and shut down in times of starvation. Instead it attempts to smooth its activity.
The first step in this smoothing process is to measure metabolic rate. Cells do so, say Dachun Yao, Michael Brownlee (Albert Einstein College of Medicine, Bronx, NY), and colleagues, by using the glycolysis degradation product methylglyoxal to modify the structure and action of transcription factors. Overactivation of this sensing pathway by hyperglycemia may explain some diabetic symptoms.
Brownlee's group earlier found high methylglyoxal in endothelial cells bathed in high glucose. Methylglyoxal is a precursor of advanced glycation end-product (AGE) formation, a kind of covalent fouling-up of the cellular machinery. But the current finding is more specific. Methylglyoxal attaches to the transcriptional corepressor mSin3A; this brings in a sugar to modify the Sp3 factor so the corepressor complex departs....
