Reaction: [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine + NAD+ + H2O = [lipoyl-carrier protein]-L-lysine + 2''-O-lipoyl-ADP-D-ribose + nicotinamide
Other name(s): SIRT4; srtN (gene name); cobB (gene name)
Systematic name: [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine:NAD+ lipoyltranferase (NAD+-hydrolysing; 2''-O-lipoyl-ADP-D-ribose-forming)
Comments: The enzyme, a member of the sirtuin family, removes the lipoyl group from the dihydrolipoamide acyltransferase (E2) component of 2-oxo acid dehydrogenase complexes such as EC 1.2.1.104, pyruvate dehydrogenase system. The enzyme often has additional activities and can remove other modifications of lysine residues such as acetyl and biotinyl groups. cf. EC 3.5.1.138, lipoamidase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Mathias, R.A., Greco, T.M., Oberstein, A., Budayeva, H.G., Chakrabarti, R., Rowland, E.A., Kang, Y., Shenk, T. and Cristea, I.M. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159 (2014) 1615-1625. [PMID: 25525879]
2. Rowland, E.A., Greco, T.M., Snowden, C.K., McCabe, A.L., Silhavy, T.J. and Cristea, I.M. Sirtuin lipoamidase activity is conserved in bacteria as a regulator of metabolic enzyme complexes. mBio 8 (2017) e01096-17. [PMID: 28900027]
3. Betsinger, C.N. and Cristea, I.M. Mitochondrial function, metabolic regulation, and human disease viewed through the prism of sirtuin 4 (SIRT4) functions. J Proteome Res 18 (2019) 1929-1938. [PMID: 30913880]