Physiological roles of animal succinate thiokinases. Specific association of the guanine nucleotide-linked enzyme with haem biosynthesis.
The discovery of two distinct succinate thiokinases in mammalian tissues, one (G-STK) specific for GDP/GTP and the other (A-STK) for ADP/ATP, poses the question of their differential metabolic roles. Evidence has suggested that the A-STK functions in the citric acid cycle in the direction of succinyl-CoA breakdown (and ATP formation) whereas one role of the G-STK appears to be the re-cycling of succinate to succinyl-CoA (at the expense of GTP) for the purpose of ketone body activation. A third metabolic participation of succinyl-CoA is in haem biosynthesis. This communication shows that in chemically induced hepatic porphyria, when the demand for succinyl-CoA is increased, it is the level of G-STK only which is elevated, that of A-STK being unaffected. The results implicate G-STK in the provision of succinyl-CoA for haem biosynthesis, a conclusion which is further supported by the observation of a high G-STK/A-STK ratio in bone marrow.
Jenkins
T M
TM
Department of Biochemistry, University of Bath, England.
Weitzman
P D
PD
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D002417:Cattle; D056486:Chemical and Drug Induced Liver Injury; D003066:Coenzyme A Ligases / Q000502:physiology*; D003997:Dicarbethoxydihydrocollidine; D005260:Female; D005704:Gallbladder / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006418:Heme / Q000096:biosynthesis*; D008107:Liver Diseases / Q000201:enzymology*; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology; D011164:Porphyrias / Q000139:chemically induced / Q000201:enzymology*; D013389:Succinate-CoA Ligases / Q000502:physiology*
D000214:Acyl Coenzyme A; D006418:Heme; D003997:Dicarbethoxydihydrocollidine; D006160:Guanosine Triphosphate; C012046:succinyl-coenzyme A; D003066:Coenzyme A Ligases; D013389:Succinate-CoA Ligases