Tyrosine pathway

The largest flux of carbon atoms from chorismate goes into the phenylala-nine/tyrosine pathway, among others leading to lignin and important groups of secondary metabolites such as flavonoids and anthocyanins. The first enzyme in that particular pathway, chorismate mutase (CM, EC 5.4.99.5), catalyzes the conversion of chorismate to prephenate (Fig. 8). Both a cytosolic and a plastidial form have been detected in several plants (e.g., 144-147). The plastidial isoform is inhibited by phenylalanine and tyrosine, and activated by tryptophan the other isoform is not affected by these... 

The hisT gene may also figure in the regulation of other metabolic pathways. Preliminary experiments indicate that the activity of the first enzyme in valine biosynthesis, acetohydroxy acid synthetase, is about five times as high in hisT mutants as it is in wild-type Salmonella [115]. Indirect evidence for the derepression of this pathway includes the excretion of valine by hisT mutants [115] and their resistance to the amino acid analogs trifluoroleucine and )S-hydroxyleucine [113]. The tyrosine pathway may also be affected in hisT mutants, since they are also resistant to the tyrosine analog aminotyrosine [113]. 

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]. 

D. Post-Tyrosine and Post-Phenylalanine Intermediates 1. The Tyrosine Pathway... 

Fig. 1.3 TyrR regulon in L-tyrosine pathway of E. coli cell... 

Some people lack the enzymes necessary to convert L phenylalanine to L tyrosine Any L phenylalanine that they obtain from their diet is diverted along a different meta bolic pathway giving phenylpyruvic acid... 

Herbicides also inhibit 5- (9/-pymvylshikiniate synthase, a susceptible en2yme in the pathway to the aromatic amino acids, phenylalanine, tyrosine and tryptophan, and to the phenylpropanes. Acetolactate synthase, or acetohydroxy acid synthase, a key en2yme in the synthesis of the branched-chain amino acids isoleucine and valine, is also sensitive to some herbicides. Glyphosate (26), the sulfonylureas (136), and the imida2oles (137) all inhibit specific en2ymes in amino acid synthesis pathways. 

Fig. 2. Biosynthetic pathway for epinephrine, norepinephrine, and dopamine. The enzymes cataly2ing the reaction are (1) tyrosine hydroxylase (TH), tetrahydrobiopterin and O2 are also involved (2) dopa decarboxylase (DDC) with pyridoxal phosphate (3) dopamine-P-oxidase (DBH) with ascorbate, O2 in the adrenal medulla, brain, and peripheral nerves and (4) phenethanolamine A/-methyltransferase (PNMT) with. Cadenosylmethionine in the adrenal...

The abundance of many protein kinases in cells is an indication of the great importance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase genes have been recognized in yeast, and it is estimated that the human genome encodes more than 1000 different protein kinases. Tyrosine kinases (protein kinases that phosphorylate Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases). Tyrosine kinases are components of signaling pathways involved in cell-cell communication (see Chapter 34). 

Figure 8.4 Skeleton pathway leading to L-phenytalanine, tyrosine and tryptophan in Escherichia coll.

Auxotrophic mutant lack one or more enzymes involved in the synthesis of amino acids (such as tyrosine). This prevents accumulation of the amino acid and thus avoids feedback inhibition of enzymatic steps in the L-phenylalanine pathway. 

In general terms, cross talk refers to the interaction between signalling pathways, e.g. between pathways involving heterotrimeric GTP-binding proteins and tyrosine kinase pathways. 

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