SUMMARY PARAGRAPH for LPD1
LPD1 encodes dihydrolipoamide dehydrogenase, which is found in the mitochondrial matrix (4, 2) and is an essential enzyme required for the glycine cleavage system, glycolysis and TCA cycle. Lpd1p is a component of the glycine decarboxylase complex (GDC), 2-oxoglutarate dehydrogenase (OGDH), and pyruvate dehydrogenase (PDH) complexes (4, 5). Mutations in LPD1 abolish activity of the glycine decarboxylase, 2-oxoglutarate dehydrogenase, and pyruvate dehydrogenase complexes (6, 7, 8). GDC is a multienzyme complex that catalyzes the reversible oxidative cleavage of glycine into CO2 and NH3 and connects the metabolism of one, two and three-carbon compounds as shown in this pathway diagram (9). PDH catalyses the conversion of pyruvate to acetyl-CoA while OGDH catalyses the oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA, which is part of the TCA cycle (4). In order to bind to the E2 (Lat1p) core of the pyruvate dehydrogenase complex, Lpd1p (E3) requires the activity of Pdx1p (Lpd1p-binding protein; Protein X) (10).
LPD1 is subject to catabolite repression and transcription of LPD1 for release from glucose repression is activated by the HAP2/HAP3/HAP4 transcription factor complex (11). In addition, LPD1 is also regulated by the Gcn4p transcription factor under conditions of amino acid starvation (8).
Lpd1p has strong sequence similarity to dihydrolipoamide dehydrogenases in prokaryotes and mammals (2, 12). Mutations in DLD, the human dihydrolipoamide dehydrogenase gene, are responsible for some cases of lactic acidosis (maple syrup urine disease, type III) (OMIM) (13).
Last updated: 2008-04-03