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Related Concept Videos

Enzyme Kinetics01:19

Enzyme Kinetics

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Enzymes speed up reactions by lowering the activation energy of the reactants. The speed at which the enzyme turns reactants into products is called the rate of reaction. Several factors impact the rate of reaction, including the number of available reactants. Enzyme kinetics is the study of how an enzyme changes the rate of a reaction.
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
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Introduction to Enzyme Kinetics01:19

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Enzyme kinetics studies the rates of biochemical reactions. Scientists monitor the reaction rates for a particular enzymatic reaction at various substrate concentrations. Additional trials with inhibitors or other molecules that affect the reaction rate may also be performed.
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
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Enzymes02:34

Enzymes

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Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
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Kinetic Energy00:23

Kinetic Energy

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Kinetic energy is the ability of an object in motion to do work or enact change. It can take on many forms. For instance, water flowing down a waterfall has kinetic energy. In biological systems, particles of light travel and are absorbed by plants to create chemical energy. Animals consume the chemical energy and give off molecules that carry their scent through the air. They also generate kinetic energy when they run away from predators. Entire systems also possess kinetic energy, like the...
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Kinetic Molecular Theory: Molecular Velocities, Temperature, and Kinetic Energy03:07

Kinetic Molecular Theory: Molecular Velocities, Temperature, and Kinetic Energy

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The kinetic molecular theory qualitatively explains the behaviors described by the various gas laws. The postulates of this theory may be applied in a more quantitative fashion to derive these individual laws.
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Alterations in Respiration II01:30

Alterations in Respiration II

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There are numerous types of normal and abnormal respiration. Based on ventilatory movements, breathing patterns are classified as regular, deep, or shallow. Examples include Biot's breathing, Cheyne-Stokes respiration, Kussmaul's breathing, hyperventilation, and hypoventilation. Each pattern is clinically significant and aids in evaluating patients.
In Biot's breathing, the respiratory rate and depth are irregular, alternating between periods of deep gasping and apnea. Common causes...
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Updated: Jan 21, 2026

GENPLAT: an Automated Platform for Biomass Enzyme Discovery and Cocktail Optimization
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GENPLAT: an Automated Platform for Biomass Enzyme Discovery and Cocktail Optimization

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Kinetic model optimization and its application to mitigating the Warburg effect through multiple enzyme alterations.

Conor O'Brien1, Andrew Allman1, Prodromos Daoutidis1

  • 1Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Avenue SE, Minneapolis, MN, 55455-0132, USA.

Metabolic Engineering
|August 11, 2019
PubMed
Summary

This study developed a new computational framework to identify optimal enzyme combinations for metabolic engineering. The approach effectively reduced lactate production in cancer cells, a key hallmark of cancer metabolism.

Keywords:
Aerobic glycolysisCentral metabolismKinetic modelingLactateMathematical optimizationWarburg effect

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Area of Science:

  • Metabolic Engineering
  • Systems Biology
  • Cancer Metabolism

Background:

  • Rewiring complex biological networks often requires multiple genetic modifications.
  • The Warburg effect, characterized by high lactate production in cancer cells, presents a significant challenge in metabolic engineering.
  • Selecting optimal enzyme targets in metabolic pathways is computationally intensive.

Purpose of the Study:

  • To develop a novel optimization framework for identifying combinations of enzyme alterations in metabolic networks.
  • To apply this framework to a kinetic model of energy metabolism to target the Warburg effect.
  • To computationally identify enzyme modifications that reduce or eliminate lactate production while sustaining cell proliferation.

Main Methods:

  • Developed a computational optimization framework utilizing convex penalty terms instead of integer variables for improved tractability.
  • Applied the framework to a mechanistic kinetic model of cellular energy metabolism.
  • Identified combinations of three or more enzyme alternations predicted to alter metabolic flux.

Main Results:

  • The optimization framework successfully identified combinations of enzyme alterations.
  • These identified alterations substantially reduced or eliminated lactate production, characteristic of the Warburg effect.
  • The proposed modifications maintained essential cellular proliferation requirements.

Conclusions:

  • The developed optimization framework is effective for identifying multi-enzyme targets in metabolic engineering.
  • This approach offers a computationally tractable method to address complex metabolic phenotypes like the Warburg effect.
  • The findings provide a strategy for engineering cancer cell metabolism to reduce lactate production.