Mechanistic elucidation of amphetamine metabolism by tyramine oxidase from human gut microbiota using molecular dynamics simulations

  title={Mechanistic elucidation of amphetamine metabolism by tyramine oxidase from human gut microbiota using molecular dynamics simulations},
  author={Kundan Kumar and Gaurao V. Dhoke and Ashok K. Sharma and Shubham Jaiswal and Vineet K. Sharma},
  journal={Journal of Cellular Biochemistry},
  pages={11206 - 11215}
The human gut harbors diverse bacterial species in the gut, which play an important role in the metabolism of food and host health. Recent studies have also revealed their role in altering the pharmacological properties and efficacy of oral drugs through promiscuous metabolism. However, the atomistic details of the enzyme‐drug interactions of gut bacterial enzymes which can potentially carry out the metabolism of drug molecules are still scarce. A well‐known example is the FDA drug amphetamine… 
2 Citations


Mechanistic and structural insight into promiscuity based metabolism of cardiac drug digoxin by gut microbial enzyme
Mechanistic insights into the structural and promiscuity‐based metabolism of widely used cardiac drug digoxin are provided and a methodology is presented, which could be useful to confirm the promiscuit‐ based metabolism of other orally administrated drugs by gut microbial enzymes and also help in designing strategies for improving the efficacy of the drugs.
Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics
A biochemical rationale for how the proteins encoded by this operon might inactivate digoxin through substrate promiscuity is presented and it is argued that mechanistic studies will pave the way for the clinical application of this work.
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This work has developed a novel computational approach to predict the metabolic enzymes and gut bacterial species, which can potentially carry out the biotransformation of a xenobiotic/drug molecule, and is the only available approach implemented as ‘DrugBug’ tool for the prediction of xenobiotics/drug metabolism by metabolic enzymes of human gut microbiota.
Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta
The inactivation of the cardiac drug digoxin by the gut Actinobacterium Eggerthella lenta is dissect, revealing a cytochrome-encoding operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome.
Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate
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Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ
The manipulation of the gut microbiota is considered as a potential therapeutic option to treat chronic gastrointestinal disease and recently developed genomic and other tools used to study the gut microbiome are highlighted.
Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics.
Results from classic and current studies of the direct and indirect impacts of the gut microbiome on the metabolism of therapeutic drugs and diet-derived bioactive compounds are integrated to provide an initial framework from which to consider a more comprehensive view of pharmacology and nutrition.
Gut microbiota and metabolic syndrome.
Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss.
Dysbiosis of the gut microbiota in disease
Data suggest that CNS-related co-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis, and the potential to positively modulate the composition of the colonic microbiota and ameliorate disease activity through bacterial intervention.
Human gut microbes impact host serum metabolome and insulin sensitivity
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