Phenylalanine, lead effects

Micelle-forming copper complexes were found to effectively discriminate between enantiomers in the hydrolysis of a-amino esters (257). Hydrolysis of (.V)-phenylalanine p-nitrophenyl ester is 14-fold faster than its enantiomer, Eq. 223. Leucine affords 10-fold faster hydrolysis. The authors note that the micellar nature of these systems is extremely important for both rate of hydrolysis and selectivity (258). For example, the /V-mcthyl-dcrivcd ligand 419b leads to inhibition of the hydrolysis process, relative to catalysis by Cu(II) ion alone. 

L-Dopa. Dopamine itself cannot penetrate the blood-brain barrier however, its natural precursor, L-dihydroxy-phenylalanine (levodopa), is effective in replenishing striatal dopamine levels, because it is transported across the blood-brain barrier via an amino acid carrier and is subsequently decarboxy-lated by DOPA-decarboxylase, present in striatal tissue. Decarboxylation also takes place in peripheral organs where dopamine is not needed, likely causing undesirable effects (tachycardia, arrhythmias resulting from activation of Pi-adrenoceptors [p. 114], hypotension, and vomiting). Extracerebral production of dopamine can be prevented by inhibitors of DOPA-decarboxylase (car-bidopa, benserazide) that do not penetrate the blood-brain barrier, leaving intracerebral decarboxylation unaffected. Excessive elevation of brain dopamine levels may lead to undesirable reactions, such as involuntary movements (dyskinesias) and mental disturbances. 

Classic phenylketonuria (PKU) is due to deficiency of phenylalanine hydroxylase, which leads to brain damage due to the neurotoxic effects of accumulated Phe or its metabolites. 

A 1,2-shift of hydrogen in the course of aromatic hydroxylation in vivo leading to preferential retention of isotopic hydrogen in accord with primary isotope effects is widespread. Known as the NIH shift it is observed only with entry of the first of two adjacent aromatic hydroxy-groups (for example, [4 - H] phenylalanine is transformed into tyrosine with NIH shift of the C-4 tritium equally to C-3 and C-5 and retention of most of it at these sites in preference to hydrogen by primary isotope effect. Subsequent conversion into dopa involves hydroxylation at C-3 /C-5 and, not being accompanied by an NIH shift, loss of half of the tritium present in the tyrosine is observed). ... 

Human liver phenylalanine hydroxylase is a multimeric homopolymer whose catalytic activity is enhanced by phenylalanine and has a feed-forward metabolic effect. Phosphorylation of phenylalanine hydroxylase by cAMP-dependant kinase leads to increased enzyme activity and dephosphorylation has an opposite effect. Thus, glucagon and insulin have opposing effects on the catalytic activity of phenylalanine hydroxylase. 

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