guanosine-triphosphate and Porphyrias

A case of erythropoietic protoporphyria (EPP) with severe acute abdominal pain and jaundice was reported. Erythrocyte protoporphyrin (PP) levels were constantly high, and liver histology showed a slight fibrosis with inflammatory infiltration. During the investigation period of 18 months, erythrocyte PP levels closely paralleled those of serum gamma-GTP.

Topics: Acute Disease; Adult; Biopsy; Erythrocytes; Erythropoiesis; Fibrosis; Guanosine Triphosphate; Humans; Liver Diseases; Male; Porphyrias; Porphyrins

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.

Topics: Acyl Coenzyme A; Animals; Bone Marrow; Cattle; Chemical and Drug Induced Liver Injury; Coenzyme A Ligases; Dicarbethoxydihydrocollidine; Female; Gallbladder; Guanosine Triphosphate; Heme; Liver Diseases; Mice; Mitochondria, Liver; Porphyrias; Succinate-CoA Ligases