Phenyllactic acid conversion

Figure 15. Conversion of procarboxypeptidase A to carboxypeptidase A by trypsin (151). The subunits are not cyclic polypeptides. ATEEase and HPLAase represents activities of activated subunits I and II on acetyl-1-tyrosine ethyl ester and hippuryl phenyllactic acid, respectively.

More recently an alternative synthesis has been proposed (91) in which the fragments C1-C5 and C6-C10 were joint together under Stille conditions (92). Starting from the suitably protected P-methyl-aspartic acid (1) its reduction to the aldehyde and conversion to the trans vinyl iodide followed by staimylation with hexamethyldistannane in the presence of freshly prepared Pd(PPh3)4 led to the trans vinylstannane 2 (Fig. 6). The commercially available (S)-phenyllactic acid (3) was converted to the Weinreb amide which was methylated at the secondary alcohol function and then converted to the propargylic ketone (4). Syn-stereoselective... 

More recently, Kang and Storm 171) have shown that conversion of cobalt(II) carboxypeptidase A to the corresponding cobalt (III) enzyme by hydrogen peroxide oxidation is accompanied by the complete loss of peptidase activity when assayed with CbzGly-L-Phe. Nevertheless, the esterase activity, as measured by the rate of hydrolysis of 0-(N-benzoyl-Gly)-D,L-phenyllactic acid, remains unaffected by this transformation. Cobalt(III) complexes are characterized by extremely slow exchange rates due to the transformation from a d (Coll) to a... 

Mutations leading to deficiencies in enzymes are usually referred to as inborn errors of metabolism, because they involve defects in the DNA of the affected individual. Errors in enzymes that catalyze reactions of amino acids frequendy have disastrous consequences, many of them leading to severe forms of mental retardation. Phenylketonuria (PKU) is a well-known example. In this condition, phenylalanine, phenylpyruvate, phenyllactate, and phenylacetate all accumulate in the blood and urine. Available evidence suggests that phenylpyruvate, which is a phenylketone, causes mental retardation by interfering with the conversion of pyruvate to acetyl-CoA (an important intermediate in many biochemical reactions) in the brain. It is also likely that the accumulation of these products in the brain cells results in an osmotic imbalance in which water flows into the brain cells. These cells expand in size until they crush each other in the developing brain. In either case, the brain is not able to develop normally. 

Metabolic Alterations, Many of the biochemical anomalies of phenylketonuria can be explained by the inhibition or absence of phenylalanine hydroxylase. The evidence in favor of this mode of pathogenesis is both direct and indirect. The indirect evidence is based on the metabolic experiments of Jervis, who administered a variety of amino acids to phenylketonuric patients and demonstrated that only phenylalanine increases the urinary excretion of phenylalanine and all its derivatives phenylpyruvic, phenyllactic, and phenylacetic acids. These experiments suggest that the block in the phenylalanine-tyrosine pathway is located beyond phenylalanine. Since tyrosine administration to phenylketonuric patients did not produce such effects, the block was assumed to be located between phenylalanine and tyrosine. This was confirmed by isotope experiments. When labeled phenylalanine is administered to normal patients, radioactivity is soon recovered in tyrosine and in proteins. In phenylketonuric patients, most of the radioactivity is recovered in the urine, and practically none is found in the protein. The administration of phenylpyruvic acid and phenylacetic acid demonstrated that in the phenylketonuric patient there is no block in the conversion of these compounds into phenylalanine. However, the most conclusive evidence was obtained when Jervis studied autopsy specimens from normal and phenylketonuric individuals and demonstrated that phenylalanine hydroxylase activity is practically nonexistent in phenylketonuric patients [76]. 

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