Tyrosine transaminase

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

This pyridoxal-phosphate-dependent enzyme [EC 2.6.1.5], also known as tyrosine transaminase, catalyzes the reaction of L-tyrosine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-hydroxyphenylpyruvate and L-glutamate. L-Phenylalanine can act as the substrate instead of tyrosine. In some systems, the mitochondrial enzyme may be identical with aspartate aminotransferase. 

One of the earliest published attempts to create antibodies with catalytic activity had as its goal the generation of a transaminase. Raso and Stollar prepared V-(5-phosphopyridoxyl)-3 -amino-L-tyrosine 154 as a mimic of the Schiff s base intermediate that is formed during the pyridoxal-dependent transamination of tyrosine and showed that it was a site-directed inhibitor of the enzymes tyrosine transaminase and tyrosine decarboxylase.132 Partially purified polyclonal antibodies, elicited against y-globulin conjugates of the hapten, recognized both the... 

By first converting a solid hepatoma into an ascites cell line, Thompson et al. (1966) were able to establish lines in culture (hepatoma, tissue culture or HTC) which responded to dexametha-sone (a steroid hormone analogue) by induction of tyrosine transaminase, i.e. a typical liver cell response. 

The metabolic pathways of phenylalanine and tyrosine are identical, because the essential phenylalanine must be converted to tyrosine to become metabolized. Figure 20.22 illustrates this pathway, which is termed the liver pathway to distinguish it from those leading to catecholamine biosynthesis. It is localized in the cytosol, with the exception of tyrosine transaminase, which is also present in the mitochondria. 

Figure 20.22 Catabolism of phenylalanine and tyrosine. A indicates the lesion in classic phenylketonuria B indicates a tyrosinemia caused by tyrosine transaminase deficiency C indicates a tyrosinemia caused by p-hydroxyphenylpyruvate oxidase deficiency and the lesion in neonatal tyrosinemia D indicates alcaptonuria.

Kim JH and Miiier LL (1969) The functional significance of changes in activity of the enzymes, tryptophan pyrroiase and tyrosine transaminase, after induction in intact rats and in the isolated, perfused rat livei. Journal of Biological Chemistry 244,1410-16. 

Hepatic cytosolic tyrosine aminotransferase (tyrosine transaminase) deficiency produces tyrosinemia type II, an autosomal recessive trait marked by hypertyrosine-mia and tyrosinuria. Clinical manifestations may include corneal erosions and plaques, inflammation (from intracellular crystallization of tyrosine), and mental retardation. Low-tyrosine and low-phenylalanine diets are beneficial. 

A. The correct response is dihydropteridine reductase. This enzyme reduces dihydrobiopterin to tetrahydrobiopterin the obligate electron donor for phenylalanine hydroxylase. Tyrosinase is the first enzyme on the pathway to melanin. Dopamine hydroxylase and tyrosine transaminase are enzymes on other tyrosine metabohc tracts. Homogentisic acid oxidase is an enzyme on the pathway of tyrosine to fumarate and acetoacetate. 

Inhibits binding of penoxybenzamine in aorta, permeability of water, pigmentation, serotonin levels, tryptophan levels, tryptophan 2,3-dioxygenase, tyrosine hydroxylase, tyrosine transaminase. 

Kupfer D. Alteration in the magnitude of induction of tyrosine transaminase by glycocorticoids. The effects of phenobarbital, o,p -DDD and P-diethylaminoethyl diphenylpropylacetate (SKF 525A). Arch Biochem Biophys 1968 127 200-206. 

B2. Benkert, O., and Matussek, N., Influence of hydrocortisone and glucagon on liver tyrosine transaminase and on brain tyrosine, norepinephrine and serotonin. Nature (London) 288,73-75 (1970). 

G7. Greengard, O., and Gordon, M., The cofactor-mediated regulation of apoen-zyme levels in animal tissues. I. The pyridoxine induced rise of rat liver tyrosine transaminase level in vivo. J. Biol. Chem. 238, 3708-3710, (1963). 

Levitan, I. B., and T. E. Webb. 1970. Posttranscriptional control in the steroid-mediated induction of hepatic tyrosine transaminase. Science, 167 283. 

Tyrosine transaminase induction in mammalian ceUs in tissue culture. Cold Spring Harbor Symp. Quant. Biol., 31 349. 

In the presence of a-ketoglutarate and pyridoxal phosphate, tyrosine loses its amino group to yield hy-droxyphenylpyruvate. The enzyme involved in that reaction—tyrosine transaminase—has been extensively purified from dog liver, and some aspects of its... 

In evaluating food requirements in infancy, one must consider that the infant s enzymic arsenal is not equivalent to that of the adult. We have already mentioned that in guinea pigs and rats, glucose-6-phospha-tase is practically nonexistent until shortly before term, but after term it rises rapidly. In humans, phenylalanine hydroxylase is absent from liver until several weeks after term. If the formation of the enzyme molecules is completely inhibited because of a genetic defect, an inborn error of metabolism develops. In rats, tyrosine transaminase increases immediately after birth and reaches a maximum 12 hours after birth. 

Thus, for phenylalanine (Phe, F), decarboxylation and dehydration (prephenate dehydratase, EC 4.2.1.51) to phenylpyruvate is followed by transamination with either of the enzymes tyrosine transaminase (EC 2.6.1.5) or aromatic amino acid transaminase (EC 2.6.1.57). Both of these use pyridoxal as cofactor and derive the nitrogen for the amino function from glutamate (Glu, E). 

In the same scheme, a representation of the action of tyrosine transaminase (EC 2.6.1.5) acting on tyrosine (Tyr, Y) is shown. This enzyme utilizes pyridoxal phosphate to remove toe amino group from tyrosine (Tyr, Y) and transfer it to a-ketoglutarate (2-oxoglutarate) with formation of glutamate (Glu, E) from the latter and 4-hydroxyphenylpyruvate from the former. Then, 4-hydroxyphenylpyruvate decarboxylase (EC 4.1.1.80), which appears to require thiamine diphosphate and... 

E5 Tyrosine transaminase SUR, TAT, naat, CORi Arabidopsis thaliana... 

On the other hand, a-transaminases have been used extensively in the production of amino acids through kinetic resolution and asymmetric synthesis. While many studies rely on the use of an excess of cosubstrate to drive the reaction to completion, some multienzymatic approaches have been developed as well. As an example, aspartate has been used as an amino donor in a multienzymatic synthesis of L-2-aminobutyrate from L-threonine (Scheme 4.8). ° The rather complex multistep sequence started with the in situ formation of 2-ketobutyrate from L-threonine catalysed by threonine deaminase (ThrDA) from E. coli. A tyrosine transaminase (lyrAT) from E. coli converted 2-ketobutyrate and L-aspartie acid to L-2-aminobutyrate and oxaloacetate, which spontaneously decarboiq lated to give pyruvate. Since the... 

Tryptophan dioxygenase and tyrosine transaminase. This results in depletion of the tissue pools of these two amino acids, leaving an unbalanced mixture of amino acids that cannot be used for protein synthesis (section 9.2.3). 

TyrasinBtnia (neonatal tyrcsinetnial Insufficient levels of the enzyme hydroxyphenylpyruvic acid oxidase or tyrosine transaminase. Trsnsjent condhion of newtnms inixeased levels of tyrosine in blood arxl urite ttop as iriam matures not assodaled wnh specific symtoms. Tyrosine in blind and urine returns to normal as infant matures. Vitamin C helps reduce blood levels. Reduced protein intake beneficial oiieti occurs in premature babies. 

Tyrosine transaminase was purified about a hundredfold from acetone powder extracts of dog liver (the most potent source of the enzyme) by dialysis and alcohol fractionation. The presence of a phenolic hydroxyl, an alpha amino, and an alpha carboxyl group were required for a compound to be active as a substrate in this transamination system. Only the L-amino acid was attacked and the only effective keto acid is a-ketoglutaric acid. The enzyme, as would be anticipated, required pyridoxal pho hate as a coenz3rme. It contiuns copper but this apparently is unrelated to its... 

Tomkins, G. M., Thompson. E. B., Mayashi, S., Gelehrter. T., Granner. D. and Peterkofskv, B., Tyrosine transaminase induction in mammalian cells in tissue culture. Cold Spring Hart. Symp. Quant. Biol., XXXI, 349, 1966. 

Comparatively recently a sharp increase in activity of a number of liver enzymes in rats and other animals is produced by cortisone (Knox et al., 1956). This stimulation of enzyme (glutamate-tyrosine transaminase, tryptophan-pyrrolase, glucose-6-phosphatase, etc.) activity by cortisone in experiments on adrenalectomized rats was associated with the synthesis of these enzymes de novo (Kenney, 1962 Alievskaya, 1965). As might be expected, this increase in enz5mie synthesis was preceded by a sharp increase in synthesis of RNA, particularly RNA of the cell nuclei (Fig. 99) (Kenney and Kull, 1963). The RNA fraction which was stimulated corresponded in its sedimentation characteristics to fast-labeled (messenger) RNA. 

El Tyrosine transaminase E2 4-Hydroxyphenylpyruvic acid decarboxylase E3 Norcoclaurine syndiase... 

So far Group B agents appear to specifically act on XDH, although studies of other enzymes may reveal additional effects. Group C contains representative steroid hormones which induce or suppress levels of XDH and in one case (hydrocortisone) induces an increase in tyrosine transaminase. Group D contains unsaturated fatty acids including oleic, linoleic and linolenic acids. These agents suppress levels of XDH and PNP. 

This is a group of hormones, mostly steroid in nature, that have not yet been extensively studied in regard to their effects on liver XDH. Results with one (hydrocortisone) are shown in Figure 2. As can be seen, total activity is increased about 3-fold (yet specific activity is only doubled since this hormone causes an increase in liver size). Preliminary results indicate that levels of PNP are unaffected, which distinguishes these effects from those in Group A. Since cortisone is known to cause increased levels of liver tyrosine transaminase (9), coordinate control of XDH and amino acid degrading enzymes is a possibility. 

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