Detectable signals, reporting 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... 

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