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Regulation of Metabolism01:19

Regulation of Metabolism

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Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
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Allosteric Regulation01:08

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Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
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Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Enzyme Inhibition01:30

Enzyme Inhibition

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Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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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.
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Related Experiment Video

Updated: Aug 12, 2025

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

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Network regulation meets substrate modification chemistry.

Vaidhiswaran Ramesh1, Thapanar Suwanmajo1,2,3, J Krishnan1,4

  • 1Department of Chemical Engineering, Sargent Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ, UK.

Journal of the Royal Society, Interface
|February 1, 2023
PubMed
Summary
This summary is machine-generated.

Cellular information processing involves network regulation and substrate modification. Integrating these reveals emergent behaviors, preventing misleading conclusions from single-level analysis.

Keywords:
multi-level networksmultisite modificationnegative and positive feedbacknetwork regulationprotein sequestrationsignalling networksubstrate modification‌

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Cellular Signaling

Background:

  • Biochemical networks are crucial for cellular information processing, involving environmental signal transduction and substrate modification.
  • Existing research often analyzes network regulation and substrate modification independently, neglecting their interactions and impact on cellular systems behavior.

Purpose of the Study:

  • To develop a systems framework for understanding the interplay between network regulation and substrate modification in biochemical networks.
  • To investigate how feedback/feed-forward circuits and multisite protein modification interact and influence emergent cellular behaviors.

Main Methods:

  • Utilized computational, analytical, and semi-analytical approaches to model and analyze biochemical network dynamics.
  • Examined the combined effects of canonical network regulation (feedback, feed-forward) and multisite substrate modification.

Main Results:

  • Revealed distinct and unexpected interactions between substrate modification and network regulation levels.
  • Demonstrated emergent behaviors arising from the integration of these two facets of biochemical networks.
  • Showcased how focusing on only one level can lead to misleading conclusions about system behavior.

Conclusions:

  • The interplay between network regulation and substrate modification is critical for accurate understanding of cellular systems.
  • This integrated framework has significant implications for dissecting signaling networks, inferring network structures, and engineering biomolecular systems.
  • Highlights the necessity of multi-level analysis for experimental, theoretical, and data-driven studies of cellular signaling.