4-Hydroxyphenylpyruvate Dioxygenase
Homogentisic Acid
Tyrosinemias
Delftia acidovorans
Fanconi Syndrome
Cystinosis
Hemorrhagic Fever with Renal Syndrome
Fanconi Anemia
Cystine
Oculocerebrorenal Syndrome
Characterization and subcellular compartmentation of recombinant 4-hydroxyphenylpyruvate dioxygenase from Arabidopsis in transgenic tobacco. (1/55)
4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and molecular oxygen. In plants this enzyme activity is involved in two distinct metabolic processes, the biosynthesis of prenylquinones and the catabolism of tyrosine. We report here the molecular and biochemical characterization of an Arabidopsis 4HPPD and the compartmentation of the recombinant protein in chlorophyllous tissues. We isolated a 1508-bp cDNA with one large open reading frame of 1338 bp. Southern analysis strongly suggested that this Arabidopsis 4HPPD is encoded by a single-copy gene. We investigated the biochemical characteristics of this 4HPPD by overproducing the recombinant protein in Escherichia coli JM105. The subcellular localization of the recombinant 4HPPD in chlorophyllous tissues was examined by overexpressing its complete coding sequence in transgenic tobacco (Nicotiana tabacum), using Agrobacterium tumefaciens transformation. We performed western analyses for the immunodetection of protein extracts from purified chloroplasts and total leaf extracts and for the immunocytochemistry on tissue sections. These analyses clearly revealed that 4HPPD was confined to the cytosol compartment, not targeted to the chloroplast. Western analyses confirmed the presence of a cytosolic form of 4HPPD in cultured green Arabidopsis cells. (+info)Crystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway. (2/55)
BACKGROUND: In plants and photosynthetic bacteria, the tyrosine degradation pathway is crucial because homogentisate, a tyrosine degradation product, is a precursor for the biosynthesis of photosynthetic pigments, such as quinones or tocophenols. Homogentisate biosynthesis includes a decarboxylation step, a dioxygenation and a rearrangement of the pyruvate sidechain. This complex reaction is carried out by a single enzyme, the 4-hydroxyphenylpyruvate dioxygenase (HPPD), a non-heme iron dependent enzyme that is active as a homotetramer in bacteria and as a homodimer in plants. Moreover, in humans, a HPPD deficiency is found to be related to tyrosinemia, a rare hereditary disorder of tyrosine catabolism. RESULTS: We report here the crystal structure of Pseudomonas fluorescens HPPD refined to 2.4 A resolution (Rfree 27.6%; R factor 21.9%). The general topology of the protein comprises two barrel-shaped domains and is similar to the structures of Pseudomonas 2,3-dihydroxybiphenyl dioxygenase (DHBD) and Pseudomonas putida catechol 2,3-dioxygenase (MPC). Each structural domain contains two repeated betaalpha betabeta betaalpha modules. There is one non-heme iron atom per monomer liganded to the sidechains of His161, His240, Glu322 and one acetate molecule. CONCLUSIONS: The analysis of the HPPD structure and its superposition with the structures of DHBD and MPC highlight some important differences in the active sites of these enzymes. These comparisons also suggest that the pyruvate part of the HPPD substrate (4-hydroxyphenylpyruvate) and the O2 molecule would occupy the three free coordination sites of the catalytic iron atom. This substrate-enzyme model will aid the design of new inhibitors of the homogentisate biosynthesis reaction. (+info)A mouse model of renal tubular injury of tyrosinemia type 1: development of de Toni Fanconi syndrome and apoptosis of renal tubular cells in Fah/Hpd double mutant mice. (3/55)
Hereditary tyrosinemia type 1 (HT1) (McKusick 276700), a severe autosomal recessive disorder of tyrosine metabolism, is caused by mutations in the fumarylacetoacetate hydrolase gene Fah (EC 3.7.1.2), which encodes the last enzyme in the tyrosine catabolic pathway. HT1 is characterized by severe progressive liver disease and renal tubular dysfunction. Homozygous disruption of the gene encoding Fah in mice causes neonatal lethality (e.g., lethal Albino deletion c14CoS mice), an event that limits use of this animal as a model for HT1. A new mouse model was developed with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd). The Fah-/- Hpd-/- mice grew normally without evidence of liver and renal disease, and the phenotype is similar to that in Fah+/+ Hpd-/- mice. The renal tubular cells of Fah-/- Hpd-/- mice, particularly proximal tubular cells, underwent rapid apoptosis when homogentisate, the intermediate metabolite between HPD and FAH, was administered to the Fah-/- Hpd-/- mice. Simultaneously, renal tubular function was impaired and Fanconi syndrome occurred. Apoptotic death of renal tubular cells, but not renal dysfunction, was prevented by pretreatment of the animals with YVAD, a specific inhibitor of caspases. In the homogentisate-treated Fah-/- Hpd-/- mice, massive amounts of succinylacetone were excreted into the urine, regardless of treatment with inhibitors. It is suggested that apoptotic death of renal tubular cells, as induced by administration of homogentisate to Fah-/- Hpd-/- mice, was caused by an intrinsic process, and that renal apoptosis and tubular dysfunctions in tubular cells occurred through different pathways. These observations shed light on the pathogenesis of renal tubular injury in subjects with FAH deficiency. These Fah-/- Hpd-/- mice can serve as a model in experiments related to renal tubular damage. (+info)The phytotoxic lichen metabolite, usnic acid, is a potent inhibitor of plant p-hydroxyphenylpyruvate dioxygenase. (4/55)
The lichen secondary metabolite usnic acid exists as a (-) and a (+) enantiomer, indicating a alpha or beta projection of the methyl group at position 9b, respectively. (-)-Usnic caused a dose-dependent bleaching of the cotyledonary tissues associated with a decrease of both chlorophylls and carotenoids in treated plants whereas no bleaching was observed with the (+) enantiomer. (-)-Usnic acid inhibited protophorphyrinogen oxidase activity (I50 = 3 microM), but did not lead to protoporphyrin IX accumulation. Bleaching appears to be caused by irreversible inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase by (-)-usnic acid (apparent IC50 = 50 nM). (+info)Gene genealogies, cryptic species, and molecular evolution in the human pathogen Coccidioides immitis and relatives (Ascomycota, Onygenales). (5/55)
Previous genealogical analyses of population structure in Coccidioides immitis revealed the presence of two cryptic and sexual species in this pathogenic fungus but did not clarify their origin and relationships with respect to other taxa. By combining the C. immitis data with those of two of its closest relatives, the free-living saprophytes Auxarthron zuffianum and Uncinocarpus reesii, we show that the C. immitis species complex is monophyletic, indicating a single origin of pathogenicity. Cryptic species also were found in both A. zuffianum and U. reesii, indicating that they can be found in both pathogenic and free-living fungi. Our study, together with a few others, indicates that the current list of known fungal species might be augmented by a factor of at least two. However, at least in the C. immitis, A. zuffianum, and U. reesii complexes, cryptic species represent subdivisions at the tips of deep monophyletic clades and thus well within the existing framework of generic classification. An analysis of silent and expressed divergence and polymorphism values between and within the taxa identified by genealogical concordance did not reveal faster evolution in C. immitis as a consequence of adaptation to the pathogenic habit, nor did it show positive Darwinian evolution in a region of a dioxygenase gene (tcrP gene coding for 4-HPPD) known to cause antigenic responses in humans. Instead, the data suggested relative stasis, indicative of purifying selection against mostly deleterious mutations. Two introns in the same gene fragment were considerably more divergent than exons and were unalignable between species complexes but had very low polymorphism within taxa. (+info)Pharmacokinetics and pharmacodynamics of NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione) and mesotrione, inhibitors of 4-hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers. (6/55)
AIMS: NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione) and mesotrione (2-(4-methylsulphonyl-2-nitrobenzoyl)-1,3-cyclohexanedione) are inhibitors of 4-hydroxyphenyl pyruvate dioxygenase (HPPD). NTBC has been successfully used as a treatment for hereditary tyrosinaemia type 1 (HT-1), while mesotrione has been developed as an herbicide. The pharmacokinetics of the two compounds were investigated in healthy male volunteers following single oral administration. The aim of the NTBC study was to assess the bioequivalence of two different formulations and to determine the extent of the induced tyrosinaemia. The mesotrione study was performed to determine the magnitude and duration of the effect on tyrosine catabolism. Additionally, the urinary excretion of unchanged mesotrione was measured to assess the importance of this route of clearance and to help develop a strategy for monitoring occupational exposure. METHODS: A total of 28 volunteers participated in two separate studies with the compounds. In the first study, the relative bioavailability of NTBC from liquid and capsule formulations was compared and the effect on plasma tyrosine concentrations measured. In the second study the pharmacokinetics of mesotrione were determined at three doses. Plasma tyrosine concentrations were monitored and the urinary excretion of mesotrione and tyrosine metabolites was measured. RESULTS: Both compounds were well tolerated at the dose levels studied. Peak plasma concentrations of NTBC were rapidly attained following a single oral dose of 1 mg x kg(-1) body weight of either formulation and the half-life in plasma was approximately 54 h. There were no statistical differences in mean (+/- s.d.) AUC(0,infinity) (capsule 602 +/- 154 vs solution 602 +/- 146 microg x ml(-1) h) or t1/2 (capsule 55 +/- 13 vs solution 54 +/- 8 h) and these parameters supported the bioequivalence of the two formulations. Mesotrione was also rapidly absorbed, with a significant proportion of the dose eliminated unchanged in urine. The plasma half-life was approximately 1 h and was independent of dose and AUC(0,infinity) and Cmax increased linearly with dose. Following administration of 1 mg NTBC x kg(-1) in either formulation, the concentrations of tyrosine in plasma increased to approximately 1100 nmol x ml(-1). Concentrations were still approximately 8 times those of background at 14 days after dosing, but had returned to background levels within 2 months of the second dose. Administration of mesotrione resulted in an increase in tyrosine concentrations which reached a maximum of approximately 300 nmol x ml(-1) following a dose of 4 mg x kg(-1) body weight. Concentrations returned to those of background within 2 days of dosing. Urinary excretion of tyrosine metabolites was increased during the 24 h immediately following a dose of 4 mg mesotrione x kg(-1), but returned to background levels during the following 24 h period. CONCLUSIONS: NTBC and mesotrione are both inhibitors of HPPD, although the magnitude and duration of their effect on tyrosine concentrations are very different. When normalized for dose, the extent of the induced tyrosinaemia after administration of NTBC and over the duration of these studies, was approximately 400 fold greater than that following administration of mesotrione. The persistent and significant effect on HPPD following administration of NTBC make it suitable for the treatment of patients with hereditary tyrosinaemia type 1 (HT-1), whilst the minimal and transient effects of mesotrione minimize the likelihood of a clinical effect in the event of systemic exposure occurring during occupational use. (+info)Purification and properties of avian liver p-hydroxyphenylpyruvate hydroxylase. (7/55)
Avian liver p-hydroxyphenylpyruvate hydroxylase (EC 1.13.11.27) was purified to a 1000-fold increase in specific activity over crude supernatant, utilizing a substrate analogue, o-hydroxyphenylpyruvate, to stabilize the enzyme. The preparation was homogeneous with respect to sedimentation with a sedimentation velocity (s20,w) of 5.3 S. The molecular weight of the enzyme was determined to be 97,000 +/- 5,000 by sedimentation equilibrium, and the molecular weight of the subunits was determined to be 49,000 +/- 3,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis revealed heterogeneity of the purified enzyme. The multiple molecular forms were separable by isoelectric focusing, and their isoelectric points ranged from pH 6.8 to 6.0. The amino acid compositions and tryptic peptide maps of the three forms isolated by isoelectric focusing were very similar. The forms of the enzyme had the same relative activity toward p-hydroxyphenylpyruvate and phenylpyruvate. Conditions which are known to accelerate nonenzymic deamidation of proteins caused interconversion of the multiple molecular forms. Iron was the only transition metal found to be associated with the purified enzyme at significant levels. The amount of enzyme-bound iron present in equilibrium-dialyzed samples was equivalent to 1 atom of iron per enzyme subunit. Purification of the enzyme activity correlated with the purification of the enzyme-bound iron. An EPR scan of the purified enzyme gave a signal at g equal 4.33, which is characteristic of ferric iron in a rhombic ligand field. (+info)A specific role for tocopherol and of chemical singlet oxygen quenchers in the maintenance of photosystem II structure and function in Chlamydomonas reinhardtii. (8/55)
alpha-Tocopherol concentrations were determined at low and high light intensities and compared with the rate of photosynthesis, photosystem II (PS II) and its reaction center D1 protein. Blocking of tocopherol biosynthesis at the 4-hydroxyphenylpyruvate dioxygenase by the herbicide pyrazolynate led to a quick disappearance of alpha-tocopherol in high light, as well as of PS II activity and the D1 protein. Homogentisic acid rescued all activities. It is concluded that alpha-tocopherol has a continuous turnover as a scavenger of the singlet oxygen that arises from the quenching by oxygen of the triplet of the PS II reaction center and triggers the degradation of the D1 protein. Thus tocopherols are essential to keep photosynthesis active. We suggest that this is why plants make and need tocopherols. Chemical quenchers of singlet oxygen, notably diphenylamines, completely protect PS II, prevent D1 protein degradation and keep tocopherol levels even at very high light intensities. This supports the notion that 1O2 is the intermediate in light triggered D1 protein turnover. (+info)4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an enzyme that is involved in the catabolism of aromatic amino acids such as tyrosine. The gene for HPPD is located on human chromosome 12q24.11.
The HPPD enzyme catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate, which is then further metabolized in the catabolic pathway leading to fumarate and acetoacetate. Deficiencies in HPPD activity have been associated with certain genetic disorders such as tyrosinemia type III, which can result in neurological symptoms and developmental delays.
In addition to its role in normal metabolism, HPPD has also been identified as a target for herbicides that inhibit the enzyme's activity, leading to the accumulation of 4-hydroxyphenylpyruvate and other toxic intermediates that can disrupt plant growth and development.
Homogentisic acid is not a medical condition, but rather an organic compound that plays a role in certain metabolic processes. It is a breakdown product of the amino acid tyrosine, and is normally further metabolized by the enzyme homogentisate 1,2-dioxygenase.
In some individuals, a genetic mutation can result in a deficiency of this enzyme, leading to a condition called alkaptonuria. In alkaptonuria, homogentisic acid accumulates in the body and can cause damage to connective tissues, joints, and other organs over time. Symptoms may include dark urine, arthritis, and pigmentation of the ears and eyes. However, it is important to note that alkaptonuria is a rare condition, affecting only about 1 in 250,000 people worldwide.
Tyrosinemia is a rare genetic disorder that affects the way the body metabolizes the amino acid tyrosine, which is found in many protein-containing foods. There are three types of tyrosinemia, but type I, also known as hepatorenal tyrosinemia or Hawkins' syndrome, is the most severe and common form.
Tyrosinemia type I is caused by a deficiency of the enzyme fumarylacetoacetase, which is necessary for the breakdown of tyrosine in the body. As a result, toxic intermediates accumulate and can cause damage to the liver, kidneys, and nervous system. Symptoms of tyrosinemia type I may include failure to thrive, vomiting, diarrhea, abdominal pain, jaundice, and mental developmental delays.
If left untreated, tyrosinemia type I can lead to serious complications such as liver cirrhosis, liver cancer, kidney damage, and neurological problems. Treatment typically involves a low-tyrosine diet, medication to reduce tyrosine production, and sometimes liver transplantation. Early diagnosis and treatment are essential for improving outcomes in individuals with tyrosinemia type I.
"Delftia acidovorans" is a species of gram-negative, motile, aerobic bacteria that is commonly found in various environments such as soil, water, and clinical settings. It is a rod-shaped bacterium that is known to be able to degrade a wide range of organic compounds, including aromatic hydrocarbons and other pollutants.
In clinical settings, "Delftia acidovorans" has been isolated from various types of human infections, including respiratory tract infections, urinary tract infections, and bacteremia. However, it is considered to be a rare cause of infection, and its clinical significance is not well understood.
It's worth noting that the genus "Delftia" was previously classified as part of the genus "Comamonas," but was reclassified based on genetic and biochemical evidence. Therefore, some older literature may refer to this bacterium as "Comamonas acidovorans."
Fanconi syndrome is a medical condition that affects the proximal tubules of the kidneys. These tubules are responsible for reabsorbing various substances, such as glucose, amino acids, and electrolytes, back into the bloodstream after they have been filtered through the kidneys.
In Fanconi syndrome, there is a defect in the reabsorption process, causing these substances to be lost in the urine instead. This can lead to a variety of symptoms, including:
* Polyuria (excessive urination)
* Polydipsia (excessive thirst)
* Dehydration
* Metabolic acidosis (an imbalance of acid and base in the body)
* Hypokalemia (low potassium levels)
* Hypophosphatemia (low phosphate levels)
* Vitamin D deficiency
* Rickets (softening and weakening of bones in children) or osteomalacia (softening of bones in adults)
Fanconi syndrome can be caused by a variety of underlying conditions, including genetic disorders, kidney diseases, drug toxicity, and heavy metal poisoning. Treatment typically involves addressing the underlying cause, as well as managing symptoms such as electrolyte imbalances and acid-base disturbances.
Cystinosis is a rare, inherited metabolic disorder that affects primarily the eyes, kidneys, and liver. It is characterized by an abnormal accumulation of the amino acid cystine within lysosomes (cellular organelles responsible for breaking down and recycling waste products) due to a defect in the gene CTNS that encodes for a protein called cystinosin. This leads to the formation of crystals, which can cause cell damage and multi-organ dysfunction.
There are three main types of cystinosis:
1. Nephropathic or infantile cystinosis: This is the most severe form, with symptoms appearing within the first year of life. It primarily affects the kidneys, leading to Fanconi syndrome (a condition characterized by excessive loss of nutrients in urine), growth failure, and kidney dysfunction. If left untreated, it can progress to end-stage renal disease (ESRD) around the age of 10.
2. Intermediate cystinosis: This form presents during childhood with milder kidney involvement but can still lead to ESRD in adolescence or early adulthood. Eye and central nervous system abnormalities may also be present.
3. Non-nephropathic or ocular cystinosis: This is the mildest form, primarily affecting the eyes. Symptoms include photophobia (sensitivity to light), corneal opacities, and decreased vision. Kidney function remains normal in this type.
Treatment for cystinosis typically involves a combination of medications to manage symptoms and slow disease progression. Cysteamine therapy, which helps remove excess cystine from cells, is the primary treatment for all types of cystinosis. Regular monitoring and management of complications are essential to maintain quality of life and prolong survival.
Hemorrhagic Fever with Renal Syndrome (HFRS) is a group of clinically similar diseases caused by several distinct but related orthohantaviruses. The viruses are primarily transmitted to humans through inhalation of aerosols contaminated with excreta of infected rodents.
The clinical presentation of HFRS includes four phases: febrile, hypotensive, oliguric (decreased urine output), and polyuric (increased urine output). The febrile phase is characterized by fever, headache, myalgia, and abdominal pain. In the hypotensive phase, patients may experience a sudden drop in blood pressure, shock, and acute kidney injury leading to oliguria. The oliguric phase can last for days to weeks, followed by a polyuric phase where urine output increases significantly.
Additional symptoms of HFRS may include nausea, vomiting, conjunctival injection (redness), photophobia (sensitivity to light), and petechial rash (small red or purple spots on the skin caused by bleeding under the skin). In severe cases, HFRS can lead to acute renal failure, hypovolemic shock, and even death.
The severity of HFRS varies depending on the specific virus causing the infection. The most severe form of HFRS is caused by the Hantaaan virus, which has a mortality rate of up to 15%. Other viruses that can cause HFRS include Dobrava-Belgrade, Seoul, and Puumala viruses, with lower mortality rates ranging from less than 1% to about 5%.
Prevention measures for HFRS include reducing exposure to rodents and their excreta through proper food storage, waste disposal, and rodent control. Vaccines are available in some countries to prevent HFRS caused by specific viruses.
Fanconi anemia is a rare, inherited disorder that affects the body's ability to produce healthy blood cells. It is characterized by bone marrow failure, congenital abnormalities, and an increased risk of developing certain types of cancer. The condition is caused by mutations in genes responsible for repairing damaged DNA, leading to chromosomal instability and cell death.
The classic form of Fanconi anemia (type A) is typically diagnosed in childhood and is associated with various physical abnormalities such as short stature, skin pigmentation changes, thumb and radial ray anomalies, kidney and genitourinary malformations, and developmental delays. Other types of Fanconi anemia (B-G) may have different clinical presentations but share the common feature of bone marrow failure and cancer predisposition.
Bone marrow failure in Fanconi anemia results in decreased production of all three types of blood cells: red blood cells, white blood cells, and platelets. This can lead to anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count). These conditions increase the risk of infections, fatigue, and bleeding.
Individuals with Fanconi anemia have a significantly higher risk of developing various types of cancer, particularly acute myeloid leukemia (AML) and solid tumors such as squamous cell carcinomas of the head, neck, esophagus, and anogenital region.
Treatment for Fanconi anemia typically involves managing symptoms related to bone marrow failure, such as transfusions, growth factors, and antibiotics. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for bone marrow failure but carries risks of its own, including graft-versus-host disease and transplant-related mortality. Regular cancer surveillance is essential due to the increased risk of malignancies in these patients.
Cystine is a naturally occurring amino acid in the body, which is formed from the oxidation of two cysteine molecules. It is a non-essential amino acid, meaning that it can be produced by the body and does not need to be obtained through diet. Cystine plays important roles in various biological processes, including protein structure and antioxidant defense. However, when cystine accumulates in large amounts, it can form crystals or stones, leading to conditions such as cystinuria, a genetic disorder characterized by the formation of cystine kidney stones.
Oculocerebrorenal syndrome, also known as Lowe syndrome, is a rare genetic disorder that primarily affects the eyes, brain, and kidneys. It's characterized by congenital cataracts, intellectual disability, and progressive kidney disease. The condition is caused by mutations in the OCRL gene, which provides instructions for making an enzyme called phosphatidylinositol 4,5-bisphosphate 5-phosphatase. This enzyme plays a crucial role in cell signaling and trafficking within cells.
The symptoms of oculocerebrorenal syndrome can vary widely among affected individuals, but they typically include:
* Eye abnormalities: Most people with the condition are born with congenital cataracts that need to be removed soon after birth. Other eye problems may include glaucoma, strabismus (crossed eyes), and optic nerve damage, which can lead to vision loss.
* Brain abnormalities: Intellectual disability is a common feature of the condition, ranging from mild to severe. Affected individuals may also have delayed development, behavioral problems, and difficulty with coordination and movement.
* Kidney abnormalities: Progressive kidney disease is a hallmark of oculocerebrorenal syndrome. The kidneys may become enlarged and scarred, leading to kidney failure in some cases. Other kidney-related symptoms can include proteinuria (protein in the urine), hematuria (blood in the urine), and high blood pressure.
There is no cure for oculocerebrorenal syndrome, but treatments can help manage the symptoms. For example, cataract surgery can improve vision, while medications and dietary changes can help manage kidney disease. Early intervention and supportive care can also help improve outcomes for affected individuals.
"Walker" is not a medical term per se, but it is often used in the medical field to refer to a mobility aid that helps individuals who have difficulty walking independently. Walkers are typically made of lightweight metal and have four legs that provide stability and support. Some walkers come with wheels or glides on the front legs to make it easier for users to move around. They may also include brakes, seats, and baskets for added functionality.
Walkers can be beneficial for people who have mobility limitations due to various medical conditions such as arthritis, stroke, fractures, neurological disorders, or aging-related issues. Using a walker can help reduce the risk of falls, improve balance, increase independence, and enhance overall quality of life.
It is essential to consult with a healthcare professional before using a walker to ensure proper fit, adjustment, and usage techniques for maximum safety and effectiveness.
4-Hydroxyphenylpyruvate dioxygenase
4-hydroxyphenylpyruvate dioxygenase inhibitor
Nitisinone
Mesotrione
Herbicide
4-Hydroxyphenylpyruvic acid
Leucine
Hawkinsinuria
4-hydroxymandelate synthase
Homogentisic acid
Picrophilus torridus
Tyrosinemia type III
Alpha-ketoglutarate-dependent hydroxylases
Leptospermone
Tyrosinemia
Tyrosinemia type I
NIH shift
4-Hydroxyphenylpyruvate:oxygen oxidoreductase
Glutathione S-transferase
Β-Hydroxy β-methylbutyric acid
Edward I. Solomon
HPPD
List of enzymes
Lactoylglutathione lyase
HPD
Fumarylacetoacetate hydrolase
Chromosome 12
List of MeSH codes (D08)
4-Hydroxyphenylglycine
List of EC numbers (EC 1)
4-Hydroxyphenylpyruvate dioxygenase - Wikipedia
RCSB PDB - 1SQI: Structural basis for inhibitor selectivity revealed by crystal structures of plant and mammalian 4...
4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor [EPC] - N0000175809
NIH 3D - Structural basis for inhibitor selectivity revealed by crystal structures of plant and mammalian 4...
SCOPe 2.08: Species: Human (Homo sapiens) [TaxId: 9606]
Tyrosinemia: MedlinePlus Genetics
Ulrich Hartl Selected Publications | Max Planck Institute of Biochemistry
New pesticides for BCPC's global database - BCPC British Crop Production Council : BCPC British Crop Production Council
Orfadin (Nitisinone Capsules and Oral Suspension): Uses, Dosage, Side Effects, Interactions, Warning
Fenquinotrione (Ref: KUH-110)
Toxics | Free Full-Text | Emerging Contaminant Imidacloprid in Mediterranean Soils: The Risk of Accumulation Is Greater than...
Control of Glyphosate-Resistant Giant Ragweed (Ambrosia trifida L.) with Isoxaflutole and Metribuzin Tankmix
Find Research outputs - University of Illinois Urbana-Champaign
Hager, A. G.<...
Storage Update for Orfadin Capsules - MPR
Multiple resistant Amaranthus tuberculatus (=A. rudis) from Canada, Ontario
Multiple resistant Amaranthus tuberculatus (=A. rudis) from United States, Illinois
HRAC Group 2</b> <font size='2'> (Legacy B) </font> resistant Amaranthus tuberculatus (=A. rudis) from United...
HRAC Group 5</b> <font size='2'> (Legacy C1 C2) </font> resistant Echinochloa crus-galli var. crus-galli from United...
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NITYR - Drug Information from Guideline Central
Multiple resistant Amaranthus retroflexus from United States, North Carolina
Multiple resistant Amaranthus tuberculatus (=A. rudis) from Canada, Ontario
HRAC Group 4</b> <font size='2'> (Legacy O) </font> resistant Echinochloa crus-galli var. crus...
Multiple resistant Amaranthus tuberculatus (=A. rudis) from Canada, Ontario
Fanconi Syndrome: Practice Essentials, Background, Pathophysiology
Palmer Amaranth | Minnesota Department of Agriculture
setaria faberi usda
HPPD3
- 4-Hydroxyphenylpyruvate dioxygenase (HPPD), also known as α-ketoisocaproate dioxygenase (KIC dioxygenase), is an Fe(II)-containing non-heme oxygenase that catalyzes the second reaction in the catabolism of tyrosine - the conversion of 4-hydroxyphenylpyruvate into homogentisate. (wikipedia.org)
- The herbicide functions by inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD). (bcpc.org)
- Populations of Palmer amaranth have been documented with resistance to one or more of the following classes: Dinitroanilines, triazines, ALS (acetolactate synthase) inhibitors, glyphosate and HPPD (4-hydroxyphenylpyruvate dioxygenase) inhibitor herbicide. (mn.us)
Inhibitor5
- The table contains 22 products whose active ingredient are classified under the same pharmacologic class 4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor [EPC]. (ndclist.com)
- Orfadin (nitisinone) is a hydroxyphenyl- pyruvate dioxygenase inhibitor used to treat a rare genetic condition called hereditary tyrosinemia type 1 ( HT -1). (rxlist.com)
- ORFADIN contains nitisinone, which is a hydroxyphenyl- pyruvate dioxygenase inhibitor indicated as an adjunct to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1 ( HT -1). (rxlist.com)
- Orfadin, a 4-hydroxyphenylpyruvate dioxygenase inhibitor, is indicated for the treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. (empr.com)
- Nitisinone (NTBC), a potent inhibitor of the 4-hydroxyphenylpyruvate dioxygenase (HPD) enzyme, rescues HT1 patients from severe illness and death. (edgehill.ac.uk)
Enzyme2
- The HPD gene provides instructions for making the 4-hydroxyphenylpyruvate dioxygenase enzyme, which performs the second step. (medlineplus.gov)
- Cai, Z.^, Ma, S.^ Loss of tyrosine catabolic enzyme 4-hydroxyphenylpyruvate dioxygenase HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer. (edu.hk)
Tyrosine1
- A significantly increased excretion of aberrant tyrosine metabolites was detected, with 4-oxo-6-hydroxyheptanoic acid as the dominant metabolite. (biomedcentral.com)
Oxidase2
- Multiple resistance has evolved to herbicides in the Groups 2 (Legacy B), Inhibition of Protoporphyrinogen Oxidase HRAC Group 14 (Legacy E), and Inhibition of Hydroxyphenyl Pyruvate Dioxygenase HRAC Group 27 (Legacy F2). (weedscience.com)
- These particular biotypes are known to have resistance to fomesafen, imazamethabenz-methyl, lactofen, mesotrione, and thifensulfuron-methyl and they may be cross-resistant to other herbicides in the Groups 2 (Legacy B), Inhibition of Protoporphyrinogen Oxidase HRAC Group 14 (Legacy E), and Inhibition of Hydroxyphenyl Pyruvate Dioxygenase HRAC Group 27 (Legacy F2). (weedscience.com)
Herbicide1
- Mesotrione, a 4-hydroxyphenylpyruvate dioxygenase-inhibiting herbicide, is labeled for PRE and POST crabgrass control. (cambridge.org)
Homogentisate3
- The shift, accounts for the observation that C3 is bonded to C4 in 4-hydroxyphenylpyruvate but to C5 in homogentisate. (wikipedia.org)
- In nearly all aerobic beings, 4-hydroxyphenylpyruvate dioxygenase is responsible for converting 4-hydroxyphenylpyruvate into homogentisate. (wikipedia.org)
- Identification of 11 Novel Homogentisate 1,2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database. (medscape.com)
Gene1
- Single gene expression heat map analysis revealed that exogenous Spd upregulated the expression of genes encoding zinc-iron transporter protein and 2'-deoxymugineic-acid 2'-dioxygenase, which improved the uptake and utilization of iron by the root system. (bvsalud.org)
Glyphosate2
- Glyphosate-resistant (GR) giant ragweed can be controlled in soybean with glyphosate plus 2,4-D ester or amitrole applied preplant. (scirp.org)
- Four field experiments were conducted in 2021 and 2022 to ascertain the effect of glufosinate rate and the addition of ammonium sulfate on annual weed control in glyphosate/glufosinate/2,4-D-resistant soybean. (cambridge.org)
Protein1
- TIM barrel domain, Glyoxalase/fosfomycin resistance/dioxygenase domain, Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily [InterProScan]. (ntu.edu.sg)
Inhibits1
- Inhibits 4-hydroxyphenylpyruvate dioxygenase, which mediates formation of homogentisic acid. (medscape.com)
Inositol 1,4,5-trisphosphate1
- inositol 1,4,5-trisphosphate receptor t. (gsea-msigdb.org)
Synthase6
- Potential anti-infective targets in pathogenic yeasts: Structure and properties of 3,4-dihydroxy-2-butanone 4-phosphate synthase of Candida albicans. (mpg.de)
- Metal sites in 3,4-dihydroxy-2-butanone 4-phosphate synthase from Methanococcus jannaschii in complex with the substrate ribulose 5-phosphate. (mpg.de)
- Structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase from Methanococcus jannaschii in complex with divalent metal ions and the substrate ribulose 5-phosphate - Implications for the catalytic mechanism. (mpg.de)
- Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC) - Implications for the catalytic mechanism and anti-malaria drug development. (mpg.de)
- Biosynthesis of riboflavin in archaea studies on the mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase of Methanococcus jannaschii. (mpg.de)
- Structure of 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. (mpg.de)
Nitisinone2
- In patients 5 years of age and older who have undetectable serum and urine succinylacetone concentrations after a minimum of 4 weeks on astable dosage of nitisinone, the total daily dose may be given once daily. (guidelinecentral.com)
- If succinylacetone is still detectable in blood or urine 4 weeks after the start of nitisinone treatment, increase the NITYR dosage to 0.75 mg/kg twice daily. (guidelinecentral.com)
Resistance1
- In China this weed first evolved resistance to Group 4 (Legacy O) herbicides in 2000 and infests Rice. (weedscience.com)
Species2
- Comparison of Setaria species in Canada Character S.italica S.faberi S.pumila S.viridis S.verticillata Culms(cm) 100 250 50 200 30 130 20 250 30 100 Ligules(mm) 1 229 11 2to1 Blades(mmwide) 10 30 10 20 4 10 4 25 5 15 USDA Natural Resources Conservation Service. (luleaccordion.se)
- The addition of ammonium sulfate to glufosinate increased control of common lambsquarters, 2 and 8 wk after application (WAA), and of foxtail species, 2, 4, and 8 WAA, but did not improve control of common ragweed and redroot pigweed. (cambridge.org)
Activity2
- The most significant part of the GO enrichment analysis shifted from responding to organic cyclic compounds and aldehyde/ketone group transferase activity to responding to trivalent iron ions and 2'-deoxymugineic-acid 2'-dioxygenase activity. (bvsalud.org)
- 10). These values are in accordance with a normal 4-hydroxyphenylpyruvate dioxygenase activity (Table 1). (biomedcentral.com)
Domain1
- C-type lectin domain family 4 member F. (gsea-msigdb.org)
Beta1
- beta-1,3-galactosyltransferase 4 [Sour. (gsea-msigdb.org)
Control1
- Field experiments evaluated the control of GR giant ragweed with IFT plus MTZ in tank-mix in a 1:4 ratio. (scirp.org)
1.13.11.273
- 4-hydroxyphenylpyruvate dioxygenase (HPD) (EC 1.13.11.27) is a key enzyme involved in tyrosine catabolism. (nih.gov)
- We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. (nih.gov)
- It has a role as a herbicide, an agrochemical, an EC 1.13.11.27 ( 4-hydroxyphenylpyruvate dioxygenase) inhibitor and a carotenoid biosynthesis inhibitor. (baynoe.com)
Inhibitor7
- In addition to dietary treatment, some advise the use of NTBC, which is a highly potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase. (medscape.com)
- Highly potent reversible inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase. (medscape.com)
- In addition to dietary treatment, appropriate medical therapy involves the use of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a highly potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase. (medscape.com)
- Nitisinone capsules are a hydroxy-phenylpyruvate dioxygenase inhibitor indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. (nih.gov)
- In this study, we kept 14CoS/14CoS mice alive for 60 d with oral 2-(2-nitro-4-trifluoromethyl-benzyol)-1,3-cyclohexanedione (NTBC), an inhibitor of p-hydroxyphenylpyruvate dioxygenase, second enzyme in the tyrosine catabolic pathway. (nih.gov)
- Nitisinone (NTBC), a potent inhibitor of the 4-hydroxyphenylpyruvate dioxygenase (HPD) enzyme, rescues HT1 patients from severe illness and death. (edgehill.ac.uk)
- A potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD) that is rapily metabolised by corn to non-active substances, it is used as a herbicide for the treatment of broadleaf weeds. (baynoe.com)
Conversion of 4-hydroxyphenylpyruvate2
Homogentisic acid2
- The HPD gene mutations that cause hawkinsinuria result in decreased enzyme activity so that 4-hydroxyphenylpyruvate is not efficiently converted to homogentisic acid. (medlineplus.gov)
- Inhibits 4-hydroxyphenylpyruvate dioxygenase, which mediates formation of homogentisic acid. (medscape.com)
Hpdl1
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. (univaq.it)
Tyrosinemia3
- Ruetschi U, Cerone R, Perez-Cerda C, Schiaffino MC, Standing S, Ugarte M, Holme E. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. (medlineplus.gov)
- An open-label study of 207 patients (aged from birth to 21.7 y, median age 9 mo) revealed an improved overall survival rate compared with historical control subjects (29% vs 88% survival probabilities at 4 y) when patients who were younger than 2 months presented with hereditary tyrosinemia type I and were treated with nitisinone and dietary restriction. (medscape.com)
- In tyrosinemia, type III (TYR III), the enzyme 4-hydrocyphenylpyruvate dioxygenase (HPD) is not working correctly. (babysfirsttest.org)
Inhibition3
- Brownlee JM, Heinz B, Bates J, Moran GR. Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. (medlineplus.gov)
- Multiple resistance has evolved to herbicides in the Groups 5 (Legacy C1 C2), and Inhibition of Hydroxyphenyl Pyruvate Dioxygenase HRAC Group 27 (Legacy F2). (weedscience.com)
- These particular biotypes are known to have resistance to atrazine, mesotrione, tembotrione, and topramezone and they may be cross-resistant to other herbicides in the Groups 5 (Legacy C1 C2), and Inhibition of Hydroxyphenyl Pyruvate Dioxygenase HRAC Group 27 (Legacy F2). (weedscience.com)
Protein1
- protein_coding" "CCP43931","fadH","Mycobacterium tuberculosis","Probable NADPH dependent 2,4-dienoyl-CoA reductase FadH (2,4-dienoyl coenzyme A reductase) (4-enoyl-CoA reductase) [Ensembl]. (ntu.edu.sg)
Atrazine1
- Therefore, five field trials were conducted over 3 yr (2019 to 2021) to determine the ED of atrazine to complement 30 g ai ha -1 of tolpyralate to achieve 80%, 90%, and 95% control of seven weed species 2, 4, and 8 wk after application (WAA). (bioone.org)
Aromatic1
- Topramezone is an aromatic ketone that is phenyl 1H-pyrazol-4-yl ketone in which the pyrazolyl group is substituted at positions 1 and 5 by methyl and hydroxy groups, respectively, and in which the phenyl group is substituted at positions 2, 3, and 4 by methyl , 4,5-dihydro-1,2-oxazol-3-yl, and methylsulfonyl groups, respectively. (baynoe.com)
Dehydratase1
- Pterin 4 alpha carbinolamine dehydratase [Interproscan]. (ntu.edu.sg)
Forms1
- Instead, some 4-hydroxyphenylpyruvate forms an unusual sulfur-containing amino acid called hawkinsin. (medlineplus.gov)
Condition1
- Some of the mutations that cause this condition change single amino acids in the 4-hydroxyphenylpyruvate dioxygenase enzyme. (medlineplus.gov)