Phenylalanine transamination processes

The low incorporation of [3- C]cinnamic acid (48) and the loss of both i-pro R) and i-pro S) protons from phenylalanine supported the participation of phenylpyruvic acid (49) in a transamination process. In addition, intermediates involving enzymatic hydroxylation at C(3) of a phenylalanine derivative were disfavored, because this type of reaction generally occurs with retention of configuration. This conclusion was confirmed by the intact incorporation of radioactive phenylpyruvic acid (49), prepared by aerobic enzymatic oxidation of (25)-[4 - H, phenylalanine with L-amino acid... 

The production of L-phenylalanine from the precursor phenylpyruvic acid by transamination is a process which requires two steps ... 

Fates of tyrosine. Tyrosine can be degraded by oxidative processes to ace-toacetate and fumarate which enter the energy generating pathways of the citric acid cycle to produce ATP as indicated in Figure 38-2. Tyrosine can be further metabolized to produce various neurotransmitters such as dopamine, epinephrine, and norepinephrine. Hydroxylation of tyrosine by tyrosine hydroxylase produces dihydroxyphenylalanine (DORA). This enzyme, like phenylalanine hydroxylase, requires molecular oxygen and telrahydrobiopterin. As is the case for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to perturbations in dihydropteridine reductase or the biopterin synthesis pathway, anyone of which could lead to interruption of tyrosine hydroxylation, an increase in tyrosine levels, and an increase in transamination of tyrosine to form its cognate a-keto acid, para-hydroxyphenylpyruvate, which also would appear in urine as a contributor to phenylketonuria. 

The key step in amino-acid biosynthesis is production of the carbon skeleton rather than the amino acid itself. Given the carbon skeleton, the process is completed by transamination. An example is shown in Reaction (21).below. In this case, the availability of phenylpyruvic acid allows production of phenylalanine. As shown, amino groups are generally provided by glutamic acid. A special system exists for the production of glutamate from a-ketoglutarate + NH4. With this basic information we can now consider specific biosyntheses. 

In our first study we attached a pyridoxamine unit to a primary carbon of jS-cyclodextrin (structure 12). We saw that pyridoxamine alone is able to transaminate pyruvic acid to form alanine, phenylpyruvic acid to form phenylalanine, and indolepyruvic acid to form tryptophan, all with equal reactivity by competition experiments. However, when the cyclodextrin was attached to the pyridoxamine there was a 200-fold preference for the indolepyruvate over pyruvate in one-to-one competition, forming greater than 98% of tryptophan, and in the competition with phenylpynivate and pyruvate the phenyManine was formed in greater than 98% as well. Thus the ability of the substrates to bind into the cyclodextrin cavity led to striking selectivities. In addition there was some chiral induction in these processes, since )3-cyclodextrin is itself chiral, but the magnitudes of the induction were quite modest. 

Basically, the shikimic acid pathway involves initial condensation of phosphoenolpyruvate (PEP) from the glycolysis process with erythrose-4-phosphate derived from the oxidative pentose phosphate cycle. A series of reactions leads to shikimic acid, which is then phosphorylated. The phosphorylated shikimic acid combines with a second molecule of PEP to yield prephenic acid via chorismic acid intermediate. Prephenic acid is then decarboxylated to form phenyl-pyruvate or p-hydroxyphenylpyruvate. On transamination, these two compounds yield phenylalanine and tyrosine, respectively. 

Instead, all the economically viable processes developed up to now are bioconversions that employ L-phenylalanine as a substrate. Metabolic pathways have been comprehensively reviewed [63] and are briefly summarized in Scheme 9.2. The most important one, known as the Ehrlich pathway, consists of three subsequent enzymatic steps (transamination, decarboxylation, and reduction), and is considered as the basis of all bioconversion processes proposed [64]. 

The essential amino acids are arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Nonessential amino acids can be produced in our bodies by transamination, a DNA-directed process of placing amino acids in proper... 

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