Linked Life Data

15581571

Source:http://linkedlifedata.com/resource/pubmed/id/15581571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-7
pubmed:abstractText
4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an Fe(II)-dependent, non-heme oxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. This reaction involves decarboxylation, substituent migration and aromatic oxygenation in a single catalytic cycle. HPPD is a member of the alpha-keto acid dependent oxygenases that typically require an alpha-keto acid (almost exclusively alpha-ketoglutarate) and molecular oxygen to either oxygenate or oxidize a third molecule. As an exception in this class of enzymes HPPD has only two substrates, does not use alpha-ketoglutarate, and incorporates both atoms of dioxygen into the aromatic product, homogentisate. The tertiary structure of the enzyme would suggest that its mechanism converged with that of other alpha-keto acid enzymes from an extradiol dioxygenase progenitor. The transformation catalyzed by HPPD has both agricultural and therapeutic significance. HPPD catalyzes the second step in the pathway for the catabolism of tyrosine, that is common to essentially all aerobic forms of life. In plants this pathway has an anabolic branch from homogentisate that forms essential isoprenoid redox cofactors such as plastoquinone and tocopherol. Naturally occurring multi-ketone molecules act as allelopathic agents by inhibiting HPPD and preventing the production of homogentisate and hence required redox cofactors. This has been the basis for the development of a range of very effective herbicides that are currently used commercially. In humans, deficiencies of specific enzymes of the tyrosine catabolism pathway give rise to a number of severe metabolic disorders. Interestingly, HPPD inhibitor/herbicide molecules act also as therapeutic agents for a number of debilitating and lethal inborn defects in tyrosine catabolism by preventing the accumulation of toxic metabolites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
433
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-28
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15581571-4-Hydroxyphenylpyruvate Dioxygenase, pubmed-meshheading:15581571-Binding Sites, pubmed-meshheading:15581571-Catalysis, pubmed-meshheading:15581571-Enzyme Activation, pubmed-meshheading:15581571-Enzyme Inhibitors, pubmed-meshheading:15581571-Ferrous Compounds, pubmed-meshheading:15581571-Holoenzymes, pubmed-meshheading:15581571-Homogentisic Acid, pubmed-meshheading:15581571-Humans, pubmed-meshheading:15581571-Hydroxylation, pubmed-meshheading:15581571-Kinetics, pubmed-meshheading:15581571-Models, Molecular, pubmed-meshheading:15581571-Models, Structural, pubmed-meshheading:15581571-Molecular Structure, pubmed-meshheading:15581571-Oxidation-Reduction, pubmed-meshheading:15581571-Oxygen, pubmed-meshheading:15581571-Protein Binding, pubmed-meshheading:15581571-Protein Structure, Tertiary, pubmed-meshheading:15581571-Pseudomonas fluorescens, pubmed-meshheading:15581571-Spectrum Analysis, Raman, pubmed-meshheading:15581571-Streptomyces, pubmed-meshheading:15581571-Substrate Specificity, pubmed-meshheading:15581571-Tyrosine
pubmed:year
2005
pubmed:articleTitle
4-Hydroxyphenylpyruvate dioxygenase.
pubmed:affiliation
Department of Chemistry and Biochemistry. University of Wisconsin-Milwaukee, 3210 N. Cramer Street, Milwaukee, WI 53211-3029, USA. moran@uwm.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Review