engleski

S-adenosylhomocysteine hydrolase deficiency: Functional analysis of a new genetic disorder in human

We have resolved the molecular basis for S-Adenosylhomocysteine hydrolase (AdoHcyase) deficiency in human. DNA analysis of individuals with extremely high levels of S-Adenosylhomocysteine (AdoHcy) showed a total of 5 different not yet characterized point mutations in the AdoHcyase gene: two point mutations, a premature stop codon and a missense mutation in 2 infants, two missense mutations in an adult with severe mental retardation, and two missense mutations in a newborn causing death at the age of 4 month (unpublished data). Additionaly, several polymorphic isoforms named SAHH-1 to 4 may be resolved by isoelectric focusing from human blood samples. Accordingly, we have identified the genetic background of human isoforms SAHH-2 and SAHH-3. To shed light on the effects of these polymorphisms on the molecular and catalytic properties of AdoHcyase, we made recombinant wild-type and polymorphic enzymes for a comparative analysis. The lecture will summarize the results of the biochemical analysis of the recombinant enzymes and discuss the impact of identified polymorphisms on the health of affected individuals.

AdoHcyase; recombinant protein; thermo sensitivity; circular dichroism; vascular disease

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