Sirtuin Catalysis and Regulation

Regulation of Sirtuin Function by Posttranslational Modifications

Sirtuins are homologs of the yeast silencing information regulator 2 protein, an NAD(+)-dependent (histone) deacetylase. In mammals seven different sirtuins, SIRT1-7, have been identified, which share a common catalytic core domain but possess distinct N- and C-terminal extensions. This core domain elicits NAD(+)-dependent deacetylase and in some cases also ADP-ribosyltransferase, demalonylase,...

Sirtuin-1 regulation of mammalian metabolism.

Sirtuin-1 (SirT1) is a nutrient-sensing deacetylase whose levels and activity increase with caloric restriction to preserve euglycemia and promote efficient energy utilization. Focusing on data obtained in vivo, we review how SirT1 orchestrates the adaptive response to fasting by stimulating hepatic gluconeogenesis and fatty acid oxidation, increasing circulating adiponectin levels and limiting...

Urea cycle regulation by mitochondrial sirtuin, SIRT5

Mammalian sirtuins have diverse roles in aging, metabolism and disease. Recently we reported a new function for SIRT5 in urea cycle regulation. Our study uncovered that SIRT5 localized to mitochondria matrix and deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 resulted in activation of CPS1 en...

Catalysis and regulation - from structure to function.

Elementary Steps in Enzyme Catalysis and Regulation

A general approach to elucidating the molecular basis of enzyme catalysis and regulation is the time resolution of the complex reaction mechanisms involved into their elementary steps. Both enzyme catalysis and enzyme regulation are initiated by the binding of small molecules to the protein. This association reaction is generally quite rapid and i often followed by a conformational change of th...