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Related Concept Videos

Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...

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Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
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Methotrexate-induced decrease in embryonic 5-methyl-tetrahydrofolate is irreversible with leucovorin supplementation.

Tseng-Ting Kao1, Gang-Hui Lee, Chi-Chang Fu

  • 1College of Medicine, National Cheng Kung University , Tainan, Taiwan.

Zebrafish
|June 14, 2013
PubMed
Summary
This summary is machine-generated.

Folate levels change dynamically during zebrafish embryo development, with tetrahydrofolate (THF) increasing and 5-methyl-tetrahydrofolate (5-CH3-THF) decreasing. Methotrexate disrupts these folate dynamics, impacting embryonic development.

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Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
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Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Nutritional Science

Background:

  • Folate is essential for rapidly developing tissues, playing a key role in biosynthesis pathways.
  • The intracellular folate pool comprises various adducts carrying one-carbon units, crucial for metabolic homeostasis.
  • Understanding folate adduct dynamics in developing embryos is critical but currently limited.

Purpose of the Study:

  • To investigate the dynamic changes of individual folate adducts during zebrafish embryogenesis.
  • To examine the impact of methotrexate exposure and leucovorin rescue on folate adduct levels and embryonic development.

Main Methods:

  • Utilized an improved high-performance liquid chromatography (HPLC) protocol for precise folate adduct quantification.
  • Employed zebrafish embryos as a model system to study developmental folate dynamics.
  • Administered methotrexate and leucovorin to assess their effects on folate metabolism and embryonic phenotypes.

Main Results:

  • Tetrahydrofolate (THF) levels increased and became dominant during zebrafish embryogenesis.
  • 5-methyl-tetrahydrofolate (5-CH3-THF) levels decreased significantly post-fertilization.
  • Methotrexate exposure reduced 5-CH3-THF, increased dihydrofolate (DHF), and induced brain ventricle anomalies, with partial rescue by leucovorin.

Conclusions:

  • Folate adducts fluctuate differentially according to developmental stage requirements.
  • Methotrexate's impact on 5-CH3-THF in embryos may affect methylation potential and epigenetics more than nucleotide synthesis.
  • Leucovorin rescue did not fully restore 5-CH3-THF levels, suggesting complex folate metabolism interactions.