HPD Mouse
Description
Functional Role and Research Applications
HPD is pivotal in cellular metabolism, particularly in regulating oxidative stress and energy production. Its dysregulation has been implicated in diseases such as cancer and tyrosinemia type I.
Mechanistic Insights
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Tyrosine metabolism: Converts 4-hydroxyphenylpyruvate to homogentisate, influencing acetyl-CoA levels and histone acetylation .
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Cancer progression: Overexpression in lung cancer promotes oxidative pentose phosphate pathway (PPP) flux, enhancing RNA/DNA synthesis and tumor growth .
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Inflammatory regulation: Links tyrosine catabolism to LKB1-AMPK signaling, modulating histone deacetylase 10 (HDAC10) localization and PPP enzyme expression .
Metabolic Impact in Lung Cancer
In in vitro and in vivo models, HPD knockdown reduced:
Genetic Blocking in FAH Mutant Mice
CRISPR-Cas9-mediated HPD knockout in fumarylacetoacetate hydrolase (FAH)-deficient mice mitigated:
| Parameter | HPD-Blocked Mice | Control Mice |
|---|---|---|
| Inflammation | Reduced oxidative stress | Severe oxidative damage |
| Survival | 100% mutants survived | High mortality in controls |
Therapeutic and Diagnostic Potential
Product Specs
4-hydroxyphenylpyruvate dioxygenase, 4-hydroxyphenylpyruvic acid oxidase, 4HPPD, HPD, HPPDase, F Alloantigen, F protein.
MGSSHHHHHH SSGLVPRGSH MGSMTTYNNK GPKPERGRFL HFHSVTFWVG NAKQAASFYC NKMGFEPLAY RGLETGSREV VSHVIKQGKI VFVLCSALNP WNKEMGDHLV KHGDGVKDIA FEVEDCDHIV QKARERGAKI VREPWVEQDK FGKVKFAVLQ TYGDTTHTLV EKINYTGRFL PGFEAPTYKD TLLPKLPRCN LEIIDHIVGN QPDQEMQSAS EWYLKNLQFH RFWSVDDTQV HTEYSSLRSI VVTNYEESIK MPINEPAPGR KKSQIQEYVD YNGGAGVQHI ALKTEDIITA IRHLRERGTE FLAAPSSYYK LLRENLKSAK IQVKESMDVL EELHILVDYD EKGYLLQIFT KPMQDRPTLF LEVIQRHNHQ GFGAGNFNSL FKAFEEEQAL RGNLTDLEPN GVRSGM.
Product Science Overview
4HPPD is a non-heme iron-containing enzyme that typically forms homodimers in eukaryotes, including mammals . The enzyme’s active site contains an iron ion, which is essential for its catalytic activity. The reaction mechanism involves the oxidative decarboxylation of 4-hydroxyphenylpyruvate, leading to the formation of homogentisate .
In mammals, 4HPPD is involved in the catabolism of tyrosine, an aromatic amino acid. The enzyme’s activity is crucial for preventing the accumulation of toxic intermediates that can result from tyrosine metabolism . Defects in the gene encoding 4HPPD can lead to metabolic disorders such as tyrosinemia type 3 and hawkinsinuria .
Recombinant 4HPPD is used in various research applications, including the study of tyrosine metabolism and the development of herbicides. In plants, 4HPPD is involved in the biosynthesis of prenylquinones, which are essential for photosynthesis . Inhibitors of 4HPPD are used as herbicides to control weed growth by disrupting this pathway .
