SIRT4 Protein, Human (GST)

SIRT4 functions as a NAD-dependent protein lipoamidase, biotinylase, deacetylase, and ADP-ribosyl transferase, with higher efficiency in removing lipoyl and biotinyl modifications than acetyl-lysine. It inhibits pyruvate dehydrogenase complex (PDH) activity by enzymatically hydrolyzing the lipoamide cofactor of DLAT in a phosphorylation-independent manner. SIRT4 also catalyzes ADP-ribosylation of target proteins like mitochondrial GLUD1, suppressing its enzymatic activity. As a negative regulator of mitochondrial glutamine metabolism, it mediates mono ADP-ribosylation of GLUD1 to inhibit anaplerosis, blocking glutamine entry into the tricarboxylic acid cycle and promoting cell cycle arrest. Its expression is repressed by mTORC1 signaling, enhancing anaplerosis and cell proliferation, while exhibiting tumor suppressor properties. Additionally, SIRT4 acts as a NAD-dependent protein deacetylase (by similar), deacetylating 'Lys-471' of MLYCD to regulate lipid homeostasis, though it does not deacetylate PC. It controls fatty acid oxidation by inhibiting PPARA transcriptional activation, likely via modulating NAD(+) levels to impair SIRT1-PPARA interaction, and downregulates insulin secretion.