We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX) preligand (S,S(P))-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination. Using the Pd-(S,S(P))-9b catalyst system, asymmetric allylic alkylation and amination proceeded very smoothly, affording the corresponding products in excellent yield with high enanti...

Liver phenylalanine hydroxylase is allosterically activated by phenylalanine. The structural changes that accompany activation have not been identified, but recent studies of the effects of phenylalanine on the isolated regulatory domain of the enzyme support a model in which phenylalanine binding promotes regulatory domain dimerization. Such a model predicts that compounds that stabilize the r...

Reversible phosphorylation is the major mechanism underlying the short-term hormonal control of phenylalanine hydroxylase activity in the liver. We report here, for the first time, the impact of a range of hormonal effectors on both the phosphorylation state and enzymic activity of phenylalanine hydroxylase present in isolated rat proximal kidney tubules. The most potent stimulator of enzyme ph...

It was previously proposed that the activation of rat liver phenylalanine hydroxylase (EC 1.14.16.1) by cAMP-dependent protein kinase-mediated phosphorylation of Ser-16 is due to the introduction of the negatively charged phosphate group. To explore the validity of this proposal, we have applied site-directed mutagenesis to specifically replace Ser-16 with negatively charged amino acids, glutam...

Several criticisms of past attempts to produce experimental phenylketonuria are discussed, and a model that appears to meet these criticisms is presented. This model uses inhibition in rats of phenylalanine hydroxylase (EC 1.14.3.1) by p-chlorophenylalanine and supplementation with phenylalanine to produce a high ratio of phenylalanine to tyrosine in their blood. By this method, an experimental...

Pigmentation during insect development is a primal adaptive requirement. In the silkworm, melanin is the primary component of larval pigments. The rate limiting substrate in melanin synthesis is tyrosine, which is converted from phenylalanine by the rate-limiting enzyme phenylalanine hydroxylase (PAH). While the role of tyrosine, derived from phenylalanine, in the synthesis of fiber proteins ha...