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Related Concept Videos

Toxic Reactions: Overview01:26

Toxic Reactions: Overview

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When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
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Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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Phase II Reactions: Miscellaneous Conjugation Reactions01:19

Phase II Reactions: Miscellaneous Conjugation Reactions

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Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
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Phosphodiester Linkages01:01

Phosphodiester Linkages

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Overview
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
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Teratogenicity01:07

Teratogenicity

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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...
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Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

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Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
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A Novel Saturation Mutagenesis Approach: Single Step Characterization of Regulatory Protein Binding Sites in RNA Using Phosphorothioates
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Sugar-Phosphate Toxicities.

Erin F Boulanger1, Anice Sabag-Daigle1, Pankajavalli Thirugnanasambantham2,3

  • 1Department of Microbial Infection and Immunity, The Ohio State Universitygrid.261331.4, Columbus, Ohio, USA.

Microbiology and Molecular Biology Reviews : MMBR
|September 29, 2021
PubMed
Summary
This summary is machine-generated.

Metabolic pathway disruptions cause toxic intermediate accumulation. Targeting specific microbial metabolic enzymes, like those in arabinose or rhamnose pathways, offers potential therapeutic strategies against pathogens.

Keywords:
antimicrobialsdrug targetsfructose-asparaginesugar phosphatetoxicity

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Area of Science:

  • Biochemistry
  • Metabolic Engineering
  • Pathogen Biology

Background:

  • Cellular metabolism generates phosphorylated intermediates.
  • Accumulation of these intermediates can lead to toxicity in hosts and pathogens.
  • Metabolic pathway inhibition, via mutation or inhibitors, can induce these toxicities.

Purpose of the Study:

  • To survey toxicities arising from various sugar and polyol metabolic pathways.
  • To identify potential novel therapeutic targets within these metabolic pathways.
  • To evaluate the feasibility of targeting conserved versus pathogen-specific metabolic vulnerabilities.

Main Methods:

  • Review and analysis of known metabolic pathways for glucose, galactose, fructose, fructose-asparagine, glycerol, trehalose, maltose, mannose, mannitol, arabinose, and rhamnose.
  • Assessment of enzyme conservation across prokaryotes, eukaryotes, and humans.
  • Discussion of existing knowledge on toxicity mechanisms and resistance.

Main Results:

  • Identified toxicities associated with the metabolism of multiple sugars and polyols.
  • Highlighted pathogen-specific metabolic enzymes (e.g., in fructose-asparagine, rhamnose, arabinose pathways) as potential drug targets.
  • Noted broad conservation of some targets (e.g., glucose, galactose) makes them less suitable for selective therapeutic intervention.

Conclusions:

  • Exploiting metabolic vulnerabilities presents a promising avenue for therapeutic development.
  • Pathogen-specific metabolic pathways offer the greatest potential for targeted drug discovery.
  • Understanding toxicity mechanisms and resistance is crucial for successful therapeutic strategies.