Enzymes regulatory mechanisms, implications

Evidence regarding the molecular mechanism by which Phe includes pathology in the PKU brain has been previously reported. Elevated levels of Phe, in the range detected in untreated PKU mice and humans (about 1200 J,), act as a moderate noncompetitive inhibitor of HMG-CoA reductase, the key regulatory enzyme in the cholesterol biosynthetic pathway (Shefer et al., 2000). Since cholesterol is a major lipid in the myelin membrane and has been implicated in signaling pathways regulating cytoskeleton in the myelin sheath (Dyer et al., 2000), a moderate inhibition of HMG-CoA reductase is likely to have a major impact on the ability of oligodendrocytes to elaborate myelin. Indeed, exposure of cultured immature... 

PRPP synthetase superactivity, diversity in the kinetic mechanisms underlying increased PRPP synthesis has been identified. This diversity has important implications for the design of methods for detection of abnormalities of the enzyme. The four categories of kinetic alteration thus far associated with PRPP synthetase superactivity in man are abnormal catalytic properties (increased maximal reaction veloc-city) 2) defective regulatory properties (purine nucleotide feedback resistance) 3) increased affinity for the substrate ribose-5-P and 4) combined alterations of catalytic and regulatory properties. 

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