Succinyl-CoA:glutarate-CoA transferase (SUGCT)

Succinyl-CoA:glutarate-CoA transferase (SUGCT) is a mitochondrial enzyme belonging to the type III CoA-transferase family[1][2]. The enzyme catalyzes the reversible transfer of CoA between succinyl-CoA and glutarate, forming glutaryl-CoA—a key step in the metabolism of lysine and tryptophan. SUGCT prevents renal excretion of glutarate by enabling its re-esterification for further degradation. The protein is required for the repair of “dead-end” metabolites in lysine catabolism, acting as a crucial genetic modifier in glutaric aciduria types 1 and 3[2][3][4]. Loss-of-function mutations result in increased urinary glutaric acid and are associated with a risk of neurological damage, especially in children. SUGCT is dimeric, with active sites at the monomer interface, and is structurally conserved within the CaiB/BaiF superfamily. Potential inhibitors (valsartan and losartan carboxylic acid) have been identified, though their relevance in vivo is unclear[2][3].

Other names

SUGCTSuccinyl-CoA:glutarate CoA-transferaseC7orf10DERP13Dicarboxyl-CoA:dicarboxylic acid coenzyme A transferase SUGCTSuccinate-hydroxymethylglutarate CoA-transferaseDermal papilla-derived protein 13ORF19GA3 candidate (by implication for glutaric aciduria type 3)

Competitive inhibition of the enzyme's active site by small molecules (e.g., losartan carboxylic acid), as demonstrated in high-throughput screening and crystallographic studies. Inhibition leads to disruption of glutarate recycling and potential accumulation of toxic metabolites.