As a subunit of SCS, SUCLG2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of GDP to GTP, as a step in the tricarboxylic acid (TCA) cycle.[6][7][8][10] The GTP generated is then consumed in anabolic pathways.[7][9] However, since GTP is not transported through the inner mitochondrial membrane in mammals and other higher organisms, it must be recycled within the matrix.[8] In addition, SUCLG2 may function in ATP generation in the absence of SUCLA2 by complexing with the mitochondrial nucleotide diphosphate kinase, nm23-H4, and thus compensate for SUCLA2 deficiency.[6][8] The reverse reaction generates succinyl-CoA from succinate to fuel ketone body and heme synthesis.[6][8]
While SCS is ubiquitously expressed, SUCLG2 is predominantly expressed in tissues involved in biosynthesis, including liver and kidney.[8][9][11] SUCLG2 has also been detected in the microvasculature of the brain, likely to support its growth.[7] Notably, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes in the brain; thus, in order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA.[7][8]
