Chapter 7: The Inductive Effect and the Control of Physiological Activities
Unveiling the Secrets of Physiological Control: The Inductive Effect, Cooperative Interactions, and Cardinal Adsorbents
As always, this is not medical advice, and reading this does not form a client relationship with me - your health is your responsibility.
Today’s Substack will continue with Chapter 7, The Association-Induction Hypothesis II: The Inductive Effect and the Control of the Physiological Activities. After some feedback, many readers were finding the summaries still too technical and full of jargon to understand. As such, I have decided to change how I present the following chapters starting with chapter 7.
Please feel free to skip to the parts you wish to read.
Summary:
“The cooperatively linked system provides the molecular basis for long-range transfer of information and energy within a cell and for physiological processes that have an all-or-none characteristic.” - What matters is the field effect, not reductionistic processes.
The chapter discusses how the inductive effect, or the ability of a molecule to influence the behavior of another molecule without direct contact, plays a key role in these processes. The chapter explores different aspects of the inductive effect, including the direct F-effect and the propagated inductive effect, and how they can be used to regulate protein activity through cooperative interactions.
The chapter introduces the concept of cardinal adsorbents, which are molecules that can adsorb onto proteins and modulate their cooperative states. Ling proposes a theoretical model for how cardinal adsorbents can control cooperative interactions and regulate protein activity in a precise and controlled manner. The model emphasizes the importance of discrete cooperative states for achieving this regulation.
The chapter also discusses the different types of cooperative interactions that can occur between proteins and ligands, including one and two receptor site systems and competitive and noncompetitive interactions. Ling highlights the role of cooperative interactions in physiological control and emphasizes the importance of understanding these interactions for developing effective therapeutic interventions.
7.1 The Inductive Effect
Ling presents many of the theories that were developed to explain the inductive effect. This section contains a fair amount of math and discussion on sigma and pi bonds, etc. However, Chiang and Tai’s theory is worth the read given the predictive power and match to experimental results. Also, their theory is still not well known in the West. The inductive effect is a type of electromagnetic effect that occurs in molecules due to the movement of electrons within the molecule. Inductive effects cause a change in the electron density of a molecule, which in turn affects the chemical properties and reactivity of that molecule.
The inductive effect is caused by the polarized nature of certain chemical bonds within a molecule. For example, a bond between two atoms of unequal electronegativity (e.g. carbon-halogen bond) will have a polarized charge distribution. Electronegativity is usually shown as a trend across and down the periodic table - electronegativity usually increases across a period L to R and down a group. The more electronegative atom pulls electrons towards itself and away from the other atom. Chemical polarity is when charges are separated in molecules creating what is called a dipole. Dipoles have one end that is negatively charged and the other that is positively charged. Polar molecules have one or more polar bonds due to the electronegativity of the atoms.
This polarization of charge in turn affects neighboring atoms and bonds within the molecule, leading to changes in electron density and chemical properties. This can result in differences in acidity or basicity, reaction rates, and other chemical properties of the molecule. This can then change a compound from acting like a Lewis acid to a Lewis base or vice versa. Lewis’ theory has to do with a transfer of electrons where most acids and bases are classified by their likelihood to transfer or accept protons (hydrogen molecules, H+).
The inductive effect can also be influenced by the presence of other functional groups, substituents in a molecule, and nearest-neighbor interactions with things external to the molecule. For example, a molecule with a highly electronegative atom such as chloride (Cl-), will have a stronger inductive effect than a molecule with a less electronegative group like a methyl group (-CH3). Overall, the inductive effect is an important factor in determining the chemical reactivity and properties of molecules. Most important to Ling’s Association Induction theory is that specifically ordered water around a protein also causes an inductive effect on molecules which then changes the protein structure and function.
7.2 The Direct F-Effect and the Molecular Mechanisms of Physiological Control
Inductive effects also occur due to the “substitution of chemical groups held together by covalent bonds…, ionic, or H bonds.” These three bonds lead to the inductive effect because they allow for the transfer of electron density between atoms. The strength of the bond can then change the reactivity and stability of the molecule
7.3 Modulation and Control of Physiological Activities
“The interaction of living systems with molecules and ions leads to characteristic variations in physiological responses; these are known by terms such as activation and inhibition, synergism and antagonism.” “The theories of Michaelis and Menten for enzyme action and of Clark for drug action describe direct competitive types of interactions but do not describe noncompetitive types of interactions.” In competitive interactions, a ligand competes with another ligand to bind to a receptor, whereas, in non-competitive interactions, the binding of a ligand to a receptor alters the conformation of the receptor and prevents the binding of another ligand. A ligand is a molecule that binds to a specific receptor site on a larger molecule, such as a protein. In the context of physiology and biochemistry, ligands can include hormones, neurotransmitters, and drugs. The binding of a ligand to its receptor can trigger a specific cellular response or signal transduction pathway.
Ling explains that in the one-receptor site system, a ligand binds to a receptor and triggers a cellular response. The one-receptor site system is the traditional model for understanding receptor-ligand interactions. However, he argues that this model is incomplete and proposes a more accurate model based on the two-receptor site system. In this model, two types of receptors with different affinities for a ligand are present. The binding of a ligand to the high-affinity receptor induces a conformational change in the receptor that enhances the binding of the ligand to the low-affinity receptor, triggering the cellular response.
7.4 Cooperativity: Molecular Basis for Controlled and Coordinated Physiological Activities
“Living beings are distinguished by their internal coherence. Physiologists are well aware of two systems that serve to maintain coherence on a macroscopic level: the nervous system and the endocrine system. Another kind of coherence exists at the microscopic, molecular level.”
Ling explains that cooperativity is a fundamental property of biological molecules and involves the interaction between multiple ligand-binding sites on a molecule. He proposes a theoretical model for cooperative interactions that involve the indirect F-effect, which is a propagated inductive effect that occurs when a ligand binds to one site and induces a conformational change that affects the binding affinity of other sites. This effect is also known as the propagated conformational change or allosteric effect. The propagated inductive effect occurs due to the polarizability of the molecule. Polarizability is a measure of the ability of a molecule or atom to develop an electric dipole moment in response to an external electric field. When a ligand binds to a specific site on the molecule, it induces a change in the distribution of electrons, leading to a change in the molecule's overall polarizability. This change in polarizability can then propagate to other parts of the molecule, affecting the binding affinity of other ligand-binding sites.
As an example, the Indirect F-Effect is seen with hemoglobin's oxygen-binding capacity. The binding of oxygen to one heme group in hemoglobin induces a conformational change that affects the binding affinity of other heme groups, leading to cooperative binding of oxygen.
Ling also discusses the yang-ling cooperative adsorption isotherm, which describes the binding of a ligand to multiple binding sites on a molecule. He argues that the control of shifts between discrete cooperative states can be achieved by the adsorption and desorption of cardinal adsorbents. Adsorbents are substances or materials that are capable of attracting and retaining other molecules or particles on their surface through a process called adsorption. This can occur through physical or chemical interactions between the adsorbent and the adsorbate molecules or particles. The discrete states are needed over continuous for regulation of processes - to create an “all-or-none” situation. The isotherm provides a useful mathematical model for understanding the cooperative binding of ligands to molecules. It has been used to explain a variety of biological phenomena, including the binding of neurotransmitters to receptors in the nervous system.
Some examples of cardinal adsorbents include: pharmaceuticals, neurotransmitters, Ca+2, and ATP. The “cardinal adsorbents affect the protein-water-ion system by a strong interaction with the proteins to produce a particular state of electronic polarization.”
Finally, Ling provides an analysis of the theoretical model of controlled cooperative interaction, which involves the regulation of shifts between cooperative states through the binding of adsorbents. He argues that this model provides a more comprehensive understanding of the molecular mechanisms of physiological control and can be applied to the development of more effective treatments for diseases and other health conditions. To analyze the model, Ling introduces the concept of the "cooperative constant," which is a measure of the degree of cooperative interaction between ligands and proteins. The cooperative constant is calculated based on the degree of cooperativity between binding sites on the protein and provides a quantitative measure of the strength of the cooperative interaction.
The practical takeaways point back to the following:
Diet and supplementation to provide the necessary constituents that make up the cardinal adsorbents
Staying physically active to help with regulation, stress release, maintenance of fascia via the piezoelectric effect, etc.
Spend time in nature and in the sunlight
Focus on sleep and sleep hygiene
Work through psychological and emotional “blocks” - german new medicine, etc.
The most important thing is to pay attention to how you feel when you implement additions or changes to these categories. If someone tells you something like “you need this” and you use it, make the change, etc. and become worse, then it’s not for you currently (or maybe ever). Pay attention to how your body, mind, and heart respond to things and use that as your guide.