Hydroxy phenylpyruvic acid

The liquid is transferred to a continuous extractor (Note 10) and extracted with ether until the supernatant layer of ether remains colorless (about 2 hours). The ethereal extract is discarded (Note 11). The aqueous solution is transferred to a 1-1. beaker and acidified by the cautious addition of 60 ml. of 121V hydrochloric acid (Note 12). The solution is returned to the extractor, which is attached to a tared round-bottomed flask. The solution is extracted with ether until no more -hydroxyphenylpyruvic acid is obtained (Note 13). The undried ether solution is evaporated to dryness on a boiling water bath to give crude p-hydroxy-phenylpyruvic acid as a pale-yellow crystalline mass. The mass is broken up with a spatula, and the flask is kept over potassium hydroxide in a vacuum desiccator until its weight is constant. The yield of crude acid is 6.9-7.2 g. (92-96%). It melts at 210— 215° (dec.) (Note 14). 

Denoya CD, DD Skinner, MR Morgenstern (1994) A Streptomyces avermitilis gene encoding a 4-hydroxy-phenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli. J Bacterial 176 5312-5319. 

Hawkinsinuria (autosomal dominant) 4-Hydroxy phenylpyruvic acid dioxygenase... 

The G. are easily recognized by their violet color reaction with concentrated sulfuric acid and are thus distinguished from pulvinic acids. The G. in fungi are formed by condensation of 2 molecules of 4-hydroxy-phenylpyruvic acid and subsequent hydroxylation steps (see also terphenylquinones). 

Biosynthesis From 4-hydroxy phenylpyruvic acid. The multi-enzyme complex p-hydroxyphenylpyruvic... 

Also in view of the results discussed earlier, it seems that inhibitors like hydroquinones, dexamethasone may increase the amount of catabolic enzymes associated with stress conditions as well as the in vivo release of phenyl radicals, facihtating depigmentation (15, 220). Stress not only releases inhibitors of tyrosinase, e.g. catecholamines, but also induces TAT in vivo (1) causing deamination of tyrosine and yielding p-hydroxy-phenylpyruvic acid, which is an inhibitor of tyrosinase. Stress has also a great effect on the immune system (127) and on brain-immune system interaction as well (179). 

Prephenate (26) is converted to phenylpyruvate (28) in many bacterial systems. In some organisms, such as Escherichia coli, prephenic acid also is oxidatively aromatized to / -hydroxyphenylpyruvic acid (29) by a soluble, NAD+-de-pendent enzyme, prephenate dehydrogenase. p-Hydroxy-phenylpyruvic acid is then transaminated by the addition of L-glutamate and pyridoxal phosphate to yield L-tyrosine (30). 

Arogenic acid is converted into phenylalanine by the action of arogenate dehydratase. Although plants normally do not appear to make phenylpyruvic acid (28) and p-hydroxy-phenylpyruvic acid (29), there is some evidence that these compounds can serve as precursors for phenylalanine and tyrosine, respectively (Jensen, 1986 Widholm, 1974). 

Udenfriend and Cooper found that the system which converts phenylalanine to tyrosine would not change phenylpyruvic acid to tyrosine. This is evidence against the proposed pathway that phenylalanine, upon deamination to phenylpyruvic acid, may be converted to p-hydroxy-phenylpyruvic acid and this, in turn, becomes reaminated to tyrosine. ... 

The substrate directly oxidized to homogentisic acid is p-hydroxy-phenylpyruvic acid. Tyrotine is not at all oxidized in the absence of a-keto-glutarate. 2,5-Dihydroxyphenylalanine, although it is converted to homogentisic acid in the alcaptonuric patient, is not attacked by the soluble enzyme system. Neither is p-hydrox3rphenylacetate nor 2,5-dihydroxy-pyruvate. 

Tyrosyluria 4-Hydroxyphenylpyruvic, 4-hydroxyphenyl-lactic and 4-hydroxyphenylacetic acids Tyrosine Delayed maturation of 4-hydroxy-phenylpyruvic acid oxidase (EC 1.13.11.27) 16.5.2... 

Biological. Reported biodegradation products include 2,3-dihydro-2,3-dihydroxybiphenyl, 2,3-dihydroxybiphenyl, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate, 2-hydroxy-3-phenyl-6-oxohexa-2,4-dienoate, 2-oxopenta-4-enoate, phenylpyruvic acid (quoted, Verschueren, 1983), 2-hydroxy-biphenyl, 4-hydroxybiphenyl, and 4,4 -dihydroxybiphenyl (Smith and Rosazza, 1974). The microbe Candida lipolytica degraded biphenyl into the following products 2-, 3-, and 4-hydroxy-biphenyl, 4,4 -dihydroxybiphenyl, and 3-methoxy-4-hydroxybiphenyl (Cerniglia and Crow, 1981). 

Additional errors of phenylalanine and tyrosine metabolism include tyrosinosis, or hereditary tyrosinemia, neonatal tyrosinemia, and alcaptonuria. In the first case, there is a probable defect in p-hydroxyphenylpyruvate oxidase. In neonatal tyrosinemia, the problem is transient and may be solved by the administration of ascorbic acid. Ascorbic acid is apparently a cofactor for p-hydroxy-phenylpyruvate oxidase. Alcaptonuria is a benign disorder in which homogen-tisic acid oxidase is inoperative and homogentisic acid is excreted in the urine. Air oxidizes the homogentisic acid to a pigment, giving urine a black color. This pigment also accumulates in the patient s tissues. 

Several modifications of the Hahn-Werner method (16) consist in condensing tryptamine (XXVI) with a phenylpyruvic acid. 3-Hydroxy-4-methoxyphenylpyruvic acid (XXVII) then yields a benzylharmane... 

Figure 55-8 Partial urine organic acid profiles 15-23 minute portion of a 33 minute run) of two patients with tyrosinemia type i. A, Acutely III patient with markedly elevated excretion of succiny[acetone, pre-NTBC treatment.The insert shows the selected ion chromatogram of the [M-15] ion of succinylacetone O-TMS-oxime TMS ester, m/z 212 B, Fifteen month old patient, succinylacetone was not detected by either total ion current (orrow) or selected ion chromatogram in three different urine specimens.This patient was later shown to be compound heterozygote for the French Canadian common splice mutation (IVS12+5G>A) and another previously unreported mutation. Peak legend I, Succinylacetone (oxime, peak I) 2, succinylacetone (oxime, peak II) 3, 4-hydroxy phenyllactic acid 4, 4-hydroxy phenylpyruvic add (oxime).The symbol marks the internal standard (pentadecanoic acid), signal abundance is normalized to the intensity of the internal standard peak.

Tyrosine Oxidation (p-Hydroxyphenylpyruvate Oxidase) (Eq. 17) The interruption of tyrosine degradation at the stage of p-hydroxy-phenylpyruvate (pHPP) in scurvy has long been considered Ae clearest evidence of a biochemical role for ascorbic acid. The intmmediate accumulates and is excreted when doses of tyrosine are given to scorbutic man, other primates, and guinea pigs, and to premature infants (K8). 

Transamination reactions, in the presence of zinc(II) ion, between (/ )-l 5-aminomethyl-I4-hydroxy-5,5-dimethyl-2,8-dilhia[9](2,5)pyridinophane1S, a pyridoxamine analog with planar chirality, and phenylpyruvic acid give (2>)-phenylalanine with 61 % ee in 76% yield17. 

All the enzymes contain ferrous iron. Ferrous ions are essential for the catalytic activity of butyrobetaine hydroxylase (259), proline-4- 254) and 3- 242, 243), hydroxylases, thymidine hydroxylase 260), lysine hydroxylase 261), trimethyllysine hydroxylase 247), thymine oxygenase 262—264), cephalosporin hydroxylase 249), and hydroxy-phenylpyruvate 265—267). In addition, the enzymes show a non-stoichio-metric requirement for ascorbic acid which is supposed to maintain the ion co-factor in the ferrous oxidation state (2, 242, 243, 254). Labelling studies with butyrobetaine hydroxylase 268), proline-4-hydroxylase 269), thymine oxygenase (270), cephalosporin hydroxylase (257) and hydroxy-phenylpyruvate hydroxylase (277) all indicate a common pattern of oxygen incorporation. One atom of oxygen becomes the new hydroxyl group while the other is located in one of the carboxylic acid groups of succinic acid. 

Figure 12.4 Simplified diagram of the general aromatic amino acid biosynthesis pathway. (Tryptophan biosynthesis proceeds from chorismate in five steps in all organisms. Phenylalanine is synthesized from arogenate or phenylpyruvate (Cyanobacteria, Saccharomyces cerevisiae, E. coli, C. glutamicum), whereas tyrosine is synthesized from arogenate or 4-hydroxy phenylpyruvate Saccharomyces cerevisiae, E. coli). In Pseudomonas aeuroginosa two alternative pathways coexist.)...

Bacteria, fungi, and plants share a common pathway for the biosynthesis of aromatic amino acids with shikimic acid as a common intermediate and therefore named after it—the shikimate pathway. Availability of shikimic acid has proven to provide growth requirements to tryptophan, tyrosine, and phenylalanine triple auxotrophic bacterial strains. Chorismate is also the last common precursor in the aromatic amino acid biosynthetic pathway, but the pathway is not named after it, as it failed to provide growth requirements to the triple auxotrophs. The aromatic biosynthetic pathway starts with two molecules of phosphoenol pyruvate and one molecule of erythrose 4-phosphate and reach the common precursor, chorismate through shikimate. From chorismate, the pathway branches to form phenylalanine and tyrosine in one and tryptophan in another. Tryptophan biosynthesis proceeds from chorismate in five steps in all organisms. Phenylalanine and tyrosine can be produced by either or both of the two biosynthetic routes. So phenylalanine can be synthesized from arogenate or phenylpyruvate whereas tyrosine can be synthesized from arogenate or 4-hydroxy phenylpyruvate. 

Working with Litsea glutinosa (Lauraceae), and concentrating on the biosynthesis of reticuline, Bhakuni and co-workers have shown that dopa and dopamine contribute only to the formation of the phenethylamine portion of reticuline. The benzylic portion is biosynthesized from 3,4-dihydroxyphenyl-pyruvic acid not derived from dopa. Tyrosine, 4-hydroxy-, and 3,4-dihydroxy-phenylpyruvic acid all participate in the formation of both halves of the molecule. Norlaudanosoline carboxylic acid, norlaudanosoline, and didehydronor-laudanosoline are intermediates in the biosynthetic sequence 0-methylation precedes W-methylation. ... 

Polyporic acid is biosynthesised by condensation of two molecules of phenylpyruvic acid in the shikimate pathway via the intermediate 2,5-diphenyl-3-hydroxy-4-oxohex-2-enoic acid and by oxidation of the resulting hydroquinone. Terphenylquinones are transformed by enzymatic reactions into pulvinic acids and many other products, some of which are also characteristic pigments of lichens and fungi. 

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