Photodynamic inactivation of selected intracellular enzymes by hematoporphyrin derivative and their relationship to tumor cell viability in vitro

The photosensitivity of freshly dissociated R3230AC mammary adenocarcinoma cells was examined by measurement of the activities of selected intracellular enzymes after treatment with hematoporphyrin derivative (Hpd) and exposure to light in vitro. Enzymes selected as representative of the cytosolic cell compartment showed no loss in activity, whereas malate dehydrogenase, located in the mitochondrial matrix, displayed a modest decrease (approximately 15%) in activity. In contrast, cytochrome c oxidase and succinate dehydrogenase, enzymes associated with the mitochondrial membrane, demonstrated a very rapid and more marked inhibition of activities, approximately 45% and 25%, respectively. The time-course of inhibition of these mitochondrial membrane enzymes preceded the loss of cell viability, which displayed slower kinetics as seen by a more gradual and progressive pattern of loss in viability. These data suggest that the mitochondria are an early-affected and important intracellular site for Hpd photosensitization.     

Lethal neonatal and severe late infantile forms of carnitine palmitoyltransferase II deficiency associated with compound heterozygosity for different protein truncation mutations

We describe a lethal neonatal form of carnitine palmitoyltransferase II (CPT II) deficiency with compound heterozygosity for 2 truncation mutations (Q413fs and 109AGC --> GCAGC). A new phenotype for a severe late infantile form of CPT II deficiency with hypoglycemia is associated with compound heterozygosity for the severe Q413fs mutation and a mild point mutation (P50H).