4- Hydroxyphenylpyruvate dioxygenase

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. 

Ruetschi U, B Odelhdg, S Lindstedt, J Barros-Soderling, B Persson, H Jornvall (1992) Characterization of 4-hydroxyphenylpyruvate dioxygenase. Primary structure of the Pseudomonas enzyme. EurJ Biochem 205 459-466. 

Yang DY. (2003) 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. Drug News Perspect 16 493 96. 

Leptospermone (34), a representative of an important new class of herbicides from the bottlebrush plant, Callistemon citrinus (Curtis) Skeels, has been found to have an inhibitory effect on the enzyme, -hydroxyphenylpyruvate dioxygenase (HPPD), involved in the synthesis of plastoquinone in plants. Nitisinone (35), a synthetic derivative of (34), has recently been introduced to the market for the treatment of hereditary tyrosinemia type 1 (HT-1), a severe genetic disease caused by a deficiency of fumaryl acetoacetate hydrolase (FAH). ... 

The molecular target site of triketone herbicides is the enzyme -hydroxyphenylpyruvate dioxygenase (HPPD). Inhibition of this enzyme disrupts the biosynthesis of carotenoids and causes a bleaching (loss of chlorophyll) effect on the foliage similar to that observed with inhibitors ofphytoene desaturase (e.g. norflurazon). However, the mechanism of action of HPPD inhibitors is different. Inhibtion of HPPD stops the synthesis of homogen tisate (HGA), which is a key precursor of the 8 different tocochromanols (tocopherols and tocotrienols) and prenyl quinones. In the absence of prenylquinone plastoquinone, phytoene desaturase activity is interrupted. The bleaching of the green tissues ensues as if these compounds inhibited phytoene desaturase. 

Lee DL, PrisbyUaMP, CromartieTH, Dagarin DP, Howard SW, Provan WM, EUis MK, Fraser T, Mutter LC, The discovery and structural requirements of inhibitors of hydroxyphenylpyruvate dioxygenase. Weed Sci 45 601—609,... 

Meazza G, Scheffler BE, Tellez MR, Rimando AM, Nanayakkara NPD, Khan LA, Abourashed EA, Romagni JG, Duke SO, Dayan EE, The inhibitory activity of natural products on plant -hydroxyphenylpyruvate dioxygenase. Phytochemistry 59 281-288, 2002. 

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. 

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... 

Operation of the NIH shift can cause migration of a large substituent as is illustrated by the hydroxylation of 4-hydroxyphenylpyruvate (Eq. 18-49), a key step in the catabolism of tyrosine (Chapter 25). Human 4-hydroxyphenylpyruvate dioxygenase is a dimer of 43-kDa subunits.439 A similar enzyme from Pseudomonas is a 150-kDa tetrameric iron-tyrosinate protein, which must be maintained in the reduced Fe(II) state for catalytic activity.440 Although this enzyme is a... 

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... 

Ellis, M. K., Whitfield, A. C., Gowans, L. A., Auton, T. R., Provan, W. M., Lock, E. A., and Smith, L. L, 1995. Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonyl-benzoyl)-cyclohexane-1,3-dione. Toxicol. Appl. Pharmacol. 133, 12-19. 

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. 

Borowski T, A Bassan, PEM Siegbahn (2004) 4-hydroxyphenylpyruvate dioxygenase A hybrid density functional study of the catalytic reaction mechanism. Biochemistry 43 (38) 12331-12342... 

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.

Lindstedt S, Holme E, Lock EA, Hjalmarson O, Strandvik B. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 1992 340 813-7. 

The amino acids phenylalanine and its hydroxylated derivative, tyrosine, are both catabolised in the livers of animals to fumaric acid and acetoacetic acid via homogentisic acid. This is formed by the oxidation of 4-hydroxyphenylpyruvate, catalysed by the copper containing enzyme 4-hydroxyphenylpyruvate dioxygenase, which requires vitamin C for its activity. The complete sequence is shown in Figure 5.13. The dioxygenase is so called because both the atoms of the... 

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