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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...
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Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
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Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
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Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
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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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Alpha-Ketoglutarate: Physiological Functions and Applications.

Nan Wu1, Mingyao Yang1, Uma Gaur1

  • 1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, P.R. China.

Biomolecules & Therapeutics
|January 14, 2016
PubMed
Summary
This summary is machine-generated.

Alpha-ketoglutarate (AKG) is a crucial molecule that supports protein synthesis and muscle health. Research shows AKG extends lifespan and delays age-related diseases by impacting cellular energy and growth pathways.

Keywords:
Alpha-ketoglutarateApplicationsFunctionsLifespan extension

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Area of Science:

  • Biochemistry
  • Metabolism
  • Aging Research

Background:

  • Alpha-ketoglutarate (AKG) is a vital intermediate in the Krebs cycle, regulating cellular respiration and nitrogen metabolism.
  • AKG serves as a precursor for glutamate and glutamine, essential for protein synthesis and muscle health.
  • It functions as a metabolic fuel for the gastrointestinal tract and plays a role in bone tissue formation.

Purpose of the Study:

  • To review the physiological functions of Alpha-ketoglutarate (AKG).
  • To summarize the diverse clinical applications and health benefits of AKG.
  • To highlight recent findings on AKG's role in lifespan extension and disease delay.

Main Methods:

  • Literature review of existing studies on AKG.
  • Analysis of AKG's biochemical pathways and metabolic roles.
  • Examination of research on AKG's effects in model organisms like Caenorhabditis elegans.

Main Results:

  • AKG stimulates protein synthesis and inhibits protein degradation, benefiting muscle and bone health.
  • AKG acts as a nitrogen scavenger and a key metabolic fuel for the gut.
  • Recent studies demonstrate AKG extends lifespan and delays age-related diseases by inhibiting ATP synthase and TOR.

Conclusions:

  • Alpha-ketoglutarate (AKG) possesses significant physiological functions with broad clinical potential.
  • AKG's role in metabolism, protein balance, and cellular pathways contributes to healthspan and lifespan.
  • Further research into AKG is warranted for its therapeutic applications in aging and disease.