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- Introduction to Protein Structure and Function
-
1. Nature’s strategies in the regulation of enzyme activity by modifiers
- Prof. Antonio Baici
- Creation of Protein Variability by Manipulation of Genes
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3. Perspectives on biological catalysis
- Prof. Stephen Benkovic
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4. Fundamentals and principles for engineering proteolytic activity
- Prof. Charles Craik
- Metabolic Diseases Caused by Genetic Mutation
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5. Modifications of pyruvate handling in health and disease
- Prof. Mary Sugden
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6. Mitochondrial fatty acid oxidation deficiencies
- Prof. Niels Gregersen
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7. Inborn errors of ketone body metabolism
- Prof. Toshiyuki Fukao
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8. Cathepsin K in bone and joint diseases
- Prof. Dieter Bromme
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9. Fabry disease: alfa-galactosidase A deficiency and enzyme replacement therapy
- Prof. David Warnock
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10. Acid beta-glucosidase/glucocerebrosidase (GCase)
- Prof. Gregory Grabowski
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11. GM2 gangliosidosis future treatments 1
- Prof. Brian Mark
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12. GM2 gangliosidosis future treatments 2
- Prof. Brian Mark
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13. The neuronal ceroid lipofuscinoses
- Prof. Sandra Hofmann
- Disorders of Blood Coagulation
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14. Advances in fibrinolysis
- Dr. Paul Kim
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16. Structure of thrombin, a Janus-headed proteinase
- Prof. Wolfram Bode
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18. Fibrinogen and factor XIII
- Prof. John Weisel
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19. Factor VIII and haemophilia A
- Dr. Geoffrey Kemball-Cook
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20. Factor IX
- Prof. Bruce Furie
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21. The biology and pathobiology of von Willebrand factor
- Prof. David Lillicrap
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22. Thrombotic thrombocytopenic purpura
- Prof. J. Evan Sadler
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23. Fibrinolysis
- Prof. Edward Tuddenham
- Other Molecular and Metabolic Disorders
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24. Glucose-6-phosphate dehydrogenase deficiency
- Dr. Jane Leopold
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25. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia
- Dr. Scott Reading
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26. Sickle cell disease
- Prof. Martin H. Steinberg
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27. Pyruvate kinase deficiency
- Prof. Alberto Zanella
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28. Heritable disorders of collagen
- Dr. Heather Yeowell
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29. Duchenne muscular dystrophy
- Prof. Jeff Chamberlain
- Archived Lectures *These may not cover the latest advances in the field
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30. Protein crystallography
- Prof. Michael James
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31. Regulation of blood coagulation by the serpin, antithrombin
- Prof. Steve Olson
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32. Rhodopsin and retinitis pigmentosa
- Dr. Shalesh Kaushal
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33. The physiology and pathology of coagulation factor XI
- Dr. David Gailani
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34. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia
- Prof. Josef Prchal
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35. Metachromatic leukodystrophy
- Prof. Volkmar Gieselmann
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36. Serpins and serpinopathies
- Dr. James Whisstock
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38. Pleiotropic and epistatic genes in sickle cell anaemia
- Prof. Ronald Nagel
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39. Genetic disorders of carbonic anhydrases II and IV
- Prof. William Sly
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40. GM2 gangliosidoses
- Prof. Don Mahuran
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41. Kinetic analysis of protein activity
- Prof. Antonio Baici
Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- The general modifier mechanism
- The general modifier mechanism: the reaction
- The principle of microscopic reversibility
- But this is impossible
- Make it easier with node compression
- Generalized microscopic reversibility
- Cleland’s definition of sticky substrate
- The original equation by Botts & Morales
- Analysis of the Botts-Morales equation
- Simplification
- Further simplification
- Rate equation when equilibrium conditions prevail
- All reactions are in steady-state (SS)
- The vertical steps are in quasi-equilibrium (QE)
- All steps are in quasi-equilibrium (QE)
- Generalized microscopic reversibility
- An assessment for the validity of quasi-equilibrium
- From the recommendations 1981
- Systematics of enzyme-modifier interactions
- Two ancestors and a prolific hybrid
- The first branch: 1 < α < ∞
- The second branch: 0 < α < 1
- The third branch: α = 1
- The basic modifier mechanisms
- Nomenclature of the basic modifier mechanisms
- Systematics = taxonomy + nomenclature
- Nature’s strategies in three specialized levels
- Allosteric interactions
- The liberator: guardian angel in enzyme-regulation
- Disclosure of the basic modifier mechanism
- Parameter dependence on modifier concentration
- The critical specific velocity
- The specific velocity equation
- The specific velocity plot (primary)
- The specific velocity plot (secondary)
- Human lipoxygenases (EC 1.13.11.-)
- Arachidonate 15-lipoxygenase (EC 1.13.11.33)
- The dual mechanisms as traffic lights
- Drug hunting and high throughput screening
- Theoretical and practical support
Topics Covered
- Regulation of enzyme activity by inhibitors and activators called modifiers
- General modifier mechanism proposed by Botts and Morales
- Fundamental laws of enzyme kinetics
- A systematic approach to a taxonomic ranking of enzyme-modifier interactions
- The pivotal role of allosteric interactions in the supervision of enzyme activity
Links
Series:
Categories:
External Links
Talk Citation
Baici, A. (2023, March 30). Nature’s strategies in the regulation of enzyme activity by modifiers [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 10, 2024, from https://doi.org/10.69645/GEKL5436.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Methods
Transcript
Please wait while the transcript is being prepared...
0:00
Welcome everybody to this
talk on the regulation of
enzyme activity by
inhibitors and activators.
My name is Antonio Baici,
retired from the
University of Zurich.
I have been active in the
field of enzyme kinetics,
investigating the
theoretical aspects
of enzyme inhibition
with obligations to
pathological degradation
of connective tissues.
0:25
In this talk, I will
bring to your attention
the kinetic groundwork of
enzyme modifier interruptions.
I will start with
the general modifier mechanism
and some principles
of enzyme kinetics.
The present nomenclature of
enzyme inhibitors and
activators is answered
dissatisfactorally, this is partly
due to the non observance of
the recommendations issued by
the International Union of
biochemistry and
Molecular Biology and
partly to merging
unrelated mechanisms
under collected names.
I will describe a
systematics treatment
of modifier mechanisms,
which is entirely based on
the recommendations and on
the general modifier mechanism.
Don't worry for names, concepts,
and the definitions
possibly new to you.
You can re-examine them on links
I will show in the last slide.
The intended purpose
of this talk
is to illustrate a
logical approach to
the investigation of enzyme
modified interactions with
emphasis on allosteric
regulation.
1:33
Jean Botts and her husband
Manuel Francisco Morales,
wrote a fundamental paper on
enzyme modifier
interactions. The term
modify in the title
declares the intention of
treating every kind of
enzyme inhibition and
activation under the same roof.
An important statement
at the beginning of
the mathematical
derivation seems to have
been underestimated by
the scientific community.
For the discussion
of this effect,
one may visualize and
enzymatic patch upon
the enzyme molecule,
consisting of an enzymatic site
which bind substrate molecules,
and then adjacent side which
binds modifier molecules.
The highlighted adjacent
side is evidently
a less spectacular definition
of allostatic site,
published 10 years later in
the famous paper by
mono and co-workers.
Moreover, Botts and Morales
published a complete
mathematical treatment,
not found on all papers.
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