Sirtuin 5 (SIRT5) (SIRT5)

Sirtuin 5 (SIRT5) is a mitochondrial enzyme belonging to the sirtuin family of NAD+-dependent deacylases. While it possesses weak deacetylase activity, its primary biological roles involve the removal of succinyl, malonyl, and glutaryl groups from lysine residues on various metabolic enzymes (UniProt Consortium, 2024). By regulating key proteins such as carbamoyl phosphate synthetase 1 (CPS1) and succinate dehydrogenase (SDH), SIRT5 acts as a central coordinator of the urea cycle, the tricarboxylic acid (TCA) cycle, and fatty acid oxidation (Nishida et al., 2015). In the context of disease, SIRT5 is often overexpressed in several cancers, where it supports metabolic reprogramming and survival under oxidative stress, making it an attractive target for small-molecule inhibition (Bringman-Rodenbarger et al., 2018). Therapeutic development is currently focused on identifying selective inhibitors to treat malignancies and potentially certain metabolic or cardiovascular conditions (Rajabi et al., 2021). SIRT5 also plays a role in cellular antioxidant defense by regulating the pentose phosphate pathway and ammonia detoxification (Polletta et al., 2015).

Other names

SIR5Sirtuin-5NAD-dependent protein deacylase sirtuin-5, mitochondrialLysine-specific desuccinylase SIRT5

SIRT5 acts as an NAD+-dependent deacylase that removes succinyl, malonyl, and glutaryl groups from lysine residues of mitochondrial proteins, thereby regulating metabolic enzyme activity.