Abstract
Tyrosinemia is a disorder of tyrosine metabolism caused by deficiency of fumarylacetoacetase (FAA) enzyme activity. The disease is characterized by progressive liver failure, transplantation is the only effective treatment. We have cultured patient hepatocytes to study the effect of FAA-deficiency on cellular metabolism. Livers from two patients were used to isolate hepatocytes, cultivation was successful in only one case. Viability of those hepatocytes was 90%, EM micrographs showed lipid inclusions and asymmetric organelle distribution. Cultures were stable, lactate dehydrogenase was normal. Protein and S-adenosylmethionine (S-ado-Met) synthesis were 30% of control values, no FAA-protein was synthesized. Previously we had found in patient liver tissue mRNA levels less than 10% of control values and low concentrations of spermine and spermidine. Experiments will be discussed to show that low S-adoMet concentrations are possibly limiting for mRNA methylation and polyamine synthesis.
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Agsteribbe, E., van Faassen, H., Hartog, M. et al. 141 PATHOGENESIS OF EREDITARY TYROSINEMIA TYPE I: METABOLID DISORDERS IN CULTURED HEPATOCYTES FROM TRANSPLANATION PATIENTS. Pediatr Res 30, 651 (1991). https://doi.org/10.1203/00006450-199112000-00171
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DOI: https://doi.org/10.1203/00006450-199112000-00171