[Specific and metabolic effect of oxythiamine]

Ukrainskii Biokhimicheskii Zhurnal (1978)
|November 1, 1981
PubMed

Insights

Oxythiamine inactivates transketolase, affecting glycolysis and the pentose phosphate pathway in rats. This biochemical action is linked to increased cyclic AMP (cAMP) signaling.

Area of Science:

  • Biochemistry
  • Enzymology
  • Metabolic pathways

Context:

  • Oxythiamine is a thiamine antagonist.
  • Transketolase is a key enzyme in the pentose phosphate pathway.
  • Understanding enzyme inhibition provides insights into metabolic regulation.

Purpose:

  • To investigate the dose-dependent effects of oxythiamine on transketolase activity in rat tissues.
  • To elucidate the biochemical mechanisms underlying oxythiamine's metabolic effects.
  • To explore the relationship between oxythiamine, glycolysis, pentose cycle intermediates, and cAMP levels.

Summary:

  • Increasing oxythiamine doses lead to transketolase inactivation in rat tissues, with a transient enzyme form being susceptible to oxythiamine pyrophosphate.
  • Oxythiamine administration results in decreased glycogen, elevated intermediates of glycolysis and the pentose cycle, and increased intracellular cAMP.
  • The study suggests that oxythiamine's biochemical action involves the activation of cAMP-dependent pathways.

Impact:

  • Provides a deeper understanding of thiamine antagonist mechanisms.
  • Highlights the role of transketolase in metabolic regulation.
  • Suggests potential therapeutic targets related to cAMP signaling in metabolic disorders.

Related Concept Videos

Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
Phase I Oxidative Reactions: Overview01:19

Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...