P-hydroxyphenylpyruvate dioxygenase

Other enzymes exhibiting this migration include cytochrome P450 and p-hydroxyphenylpyruvate dioxygenase... 

The enzyme p-hydroxyphenylpyruvate dioxygenase is involved in the conversion of p-hydroxyphenylpyruvate into homogentisate, a key step in plastoquinone biosynthesis. Inhibition of this enzyme has an indirect effect on carotenoid biosynthesis as plastoquinone is a co-factor of the enzyme phytoene desaturase. The new maize herbicide isoxaflutole and the triketone herbicides such as sulcotrione (Figure 2.7), inhibit p-hydroxyphenylpyruvate dioxygenase and this leads to the onset of bleaching in susceptible weeds and ultimately plant death.4... 

Romagni, J.G., Meazza, G, Nanayakkara, N.P.D., Dayan, F.E. The phytotoxic lichen metabolite, usnic acid, is a potent inhibitor of plant p-hydroxyphenylpyruvate dioxygenase. FEBS Letters 2000 480 301-305. 

Determination of p-hydroxyphenylpyruvate dioxygenase (HPPD) activity in vitro... 

Romagni, J. G., Meazza, G., Nanayakkara, and D., Dayan, F. E., 2000. The Phytotoxic Lichen Metabolite, Usnic Acid, is a Potent Inhibitor of Plant p-Hydroxyphenylpyruvate Dioxygenase. FEBS Letters 480 (2-3), 301-305. 

Figure 3. Effect of the p-triketone (-)-usnic acid (circles), the benzoquinone sorgoleone (triangles) and the commercial herbicide sulcotrione (squares) on the activity of p-hydroxyphenylpyruvate dioxygenase. The dotted line represents 50% inhibition of enzyme activity.

Vitamin Soybean [15] Overexpression of enzymes (chorismate mutase-prephenate dehydrogenase, homogentisate phytyltrans-ferase, and p-hydroxyphenylpyruvate dioxygenase) that are involved with the biosynthesis of vitamin E precursors (increase in tocodiromanols, including tocotrienol)... 

SCHULZ A, CRT o, BEYER P and KLEINIG H (1993) SC-0051, a 2-benzoyl-cyclohexane-l,3-dione bleaching herbicide, is a potent inhibitor of the enzyme /<-hydroxyphenylpyruvate dioxygenase , Terr, 318, 162-6. 

Lindstedt S, B Odelhbg, M Rundgren (1977) Purification and properties of 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. P. J. 874. Biochemistry 16 3369-3377. 

Dayan EE, Duke SO, Sauldubois A, Singh N, McCurdy C, Cantrell CL, -Hydroxyphenylpyruvate dioxygenase is a target site for P-triketones from Lep-tospermum scoparium Phytochemistry, 2007. 

The 2-oxoacid p-hydroxyphenylpyruvate is decar-boxylated by the action of a dioxygenase (Eq. 18-49). The product homogentisate is acted on by a second dioxygenase, as indicated in Fig. 25-5, with eventual conversion to fumarate and acetoacetate. A rare metabolic defect in formation of homogentisate leads to tyrosinemia and excretion of hawkinsin97 a compound postulated to arise from an epoxide (arene oxide) intermediate (see Eq. 18-47) which is detoxified by a glutathione transferase (Box 11-B). 

The metabolism of phenylalanine will now be considered in some detail, as two inborn errors of metabolism are known that affect this pathway. Phenylalanine is first hydroxylated by phenylalanine hydroxylase to form another aromatic amino acid tyrosine (Fig. 8). The coenzyme for this reaction is the reductant tetrahydrobiopterin which is oxidized to dihydrobiopterin. Phenylalanine hydroxylase is classified as a monooxygenase as one of the atoms of 02 appears in the product and the other in HzO. The tyrosine is then trans-aminated to p-hydroxyphenylpyruvate, which is in turn converted into homogentisate by p-hydroxyphenylpyruvate hydroxylase. This hydroxylase is an example of a dioxygenase, as both atoms of 02 become incorporated into the product (Fig. 8). The homogentisate is then cleaved by homogentisate oxidase, another dioxygenase, before fumarate and acetoacetate are produced... 

A similar reaction is catalyzed by 4-hydroxyphenylpyruvate dioxygenase (D 22). The substrate, p-hydroxyphenylpyruvic acid, possesses a keto grouping in the side chain. The oxygen molecule probably reacts first with this carbonyl group under simultaneous decarboxylation. The other oxygen atom is added to... 

It was shown by using 02 that only one of the two oxygen atoms ends up in the carbonyl group. An interesting example of this operation is the conversion of p-hydroxyphenylpyruvic acid to homogentisic acid by a dioxygenase ... 

We end this section on enzyme inhibition with a case study about 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) and disorders in tyrosine catabolism. After transamination of tyrosine, 4-hydroxyphenylpyruvate (148) is formed which is then decarboxylated, isomerized and oxygenated by HPPD to yield homogentisate (149) or by hydroxyman-delate synthase (HMS) to yield p-hydroxymandelate (150). 149 serves as the precursor for plastoquinones and tocopherols in plants . Thus, inhibitors of HPPD have been designed... 

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