Affiliations: Department of Biochemical Sciences and Laboratory of
Clinical Biochemistry, University of Rome La Sapienza, Rome, Italy | Loges-School of Physical Medicine, Bad Harzburg,
Germany
Note: [] Address for correspondence: C. Salerno, Laboratory of Clinical
Biochemistry, via dei Sardi 58, 00185 Roma, Italy. Tel./Fax: +39 064463776;
E-mail: [email protected]
Abstract: Adenylosuccinate lyase is an enzyme of fumarase superfamily that
participates in the purine biosynthetic pathway, catalysing the nonhydrolytic
cleavage of succinyl groups from SAICA ribotide and adenylosuccinate. Enzyme
defects are associated with a human inherited disease, which arises from single
point mutations to the gene and results in mild to severe psychomotor
retardation, epilepsy, muscle wasting, and autistic features. Adenylosuccinate
lyase activity is lost to a different extent in the patients. Diminished levels
of enzyme have been attributed to loss of catalytic activity, protein
instability, or environmental factors. P100A/D422Y mutation represents a
feasible model for studying the effect of cell milieu on the activity of the
impaired enzyme. The defective enzyme is inhibited by micromolar concentrations
of trans-4-hydroxy-2-nonenal (HNE), a major product of membrane peroxidation
that has been found to accumulate in brain tissues of patients with
neurodegenerative disorders. It is suggested that inactivation of defective
adenylosuccinate lyase by HNE and other membrane peroxidation products may
account, at least in part, for the impairment of neurological functions and
recurrent worsening of the symptoms.
