Сукцинил-КоА синтетазасы: қатысушы метаболизм және аурулар

Class of enzymes

Succinyl coenzyme A synthetase (SCS, also known as succinyl CoA synthetase or succinate thiokinase or succinate CoA ligase) is an enzyme that catalyzes the reversible reaction of succinyl CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule (either GTP or ATP) from an inorganic phosphate molecule and a nucleoside diphosphate molecule (either GDP or ADP). It plays a key role as one of the catalysts involved in the citric acid cycle, a central pathway in cellular metabolism, and it is located within the mitochondrial matrix of a cell.

SCS facilitates the flux of molecules into other metabolic pathways by controlling the interconversion between succinyl CoA and succinate. This is important because succinyl CoA is an intermediate necessary for porphyrin, heme, and ketone body biosynthesis.

In some bacteria, the enzyme is regulated at the transcriptional level. It has been demonstrated that the gene for SCS (sucCD) is transcribed along with the gene for α ketoglutarate dehydrogenase (sucAB) under the control of a promoter called sdhC, which is part of the succinate dehydrogenase operon. This operon is up regulated by the presence of oxygen and responds to a variety of carbon sources. Antibacterial drugs that prevent phosphorylation of histidine, like the molecule LY26650, are potent inhibitors of bacterial SCSs.

Measurements (performed using a soy bean SCS) indicate an optimal temperature of 37 °C and an optimal pH of 7.0 8.0.

Fatal infantile lactic acidosis: Defective SCS has been implicated as a cause of fatal infantile lactic acidosis, which is a disease in infants that is characterized by the build up of toxic levels of lactic acid. The condition (when it is most severe) results in death usually within 2–4 days after birth. It has been determined that patients with the condition display a two base pair deletion within the gene known as SUCLG1 that encodes the α subunit of SCS. As a result, functional SCS is absent in metabolism causing a major imbalance in flux between glycolysis and the citric acid cycle. Since the cells do not have a functional citric acid cycle, acidosis results because cells are forced to choose lactic acid production as the primary means of producing ATP.