22. Among the following which enzyme used NAD as cofactor?
(1) Histone acetyl transferase
(2) Histone methyl transferase
(3) Histone deacetylase
(4) Histone demethylase
Introduction
Histone modifications are critical for regulating chromatin structure and gene expression. Among these, histone acetylation and deacetylation dynamically modulate DNA accessibility. Histone deacetylases (HDACs) reverse acetylation marks, and a unique subclass of HDACs, called sirtuins, require NAD+ as a cofactor. This dependency links cellular metabolic status to epigenetic control.
NAD-Dependent Histone Deacetylases (Sirtuins)
Sirtuins (Class III HDACs) catalyze the removal of acetyl groups from lysine residues on histones using NAD+ as a co-substrate. The reaction couples deacetylation to the cleavage of NAD+, producing nicotinamide and O-acetyl-ADP-ribose.
This NAD-dependence allows sirtuins to act as metabolic sensors, adjusting chromatin states in response to nutrient availability and cellular energy levels.
Other Histone-Modifying Enzymes and Their Cofactors
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Histone acetyltransferases (HATs): Use acetyl-CoA to add acetyl groups.
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Histone methyltransferases: Use S-adenosylmethionine (SAM) as a methyl donor.
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Histone demethylases: Use cofactors like FAD or Fe(II)/α-ketoglutarate, but not NAD.
Biological Implications
NAD-dependent HDACs regulate processes such as aging, metabolism, stress responses, and genome stability. Their activity links epigenetic regulation to cellular metabolic states, making them important therapeutic targets.
Conclusion
Among histone-modifying enzymes, only NAD-dependent histone deacetylases (sirtuins) utilize NAD as a cofactor. This unique feature integrates metabolic signals with chromatin regulation, influencing gene expression and cellular function.
Answer:
(3) Histone deacetylase
