AN MIT PERSPECTIVE OF CONSTITUTIONAL MEDICINE

A drug substance becomes CONSTITUTIONAL MEDICINE of an individual, if it contains one or more types of chemical molecules which can “compete” with the pathogenic molecules that have produced molecular inhibitions in diverse types of biological targets causing errors in various important biochemical pathways, that are expressed through diverse trains of symptoms that belong to the classes considered to be ‘physical’ and ‘mental’ generals.

In post-avogadro dilutions, this CONSTITUTIONAL MEDICINE will contain molecular imprints of the chemical molecules contained in them, which can act as artificial binding pockets for the pathogenic molecules due to their conformational affinity, deactivate them, and remove the pathological molecular inhibitions they have produced in the body.

CONSTITUTIONAL SYMPTOMS are the expressions of disruptions in METABOLIC PATHWAYS- both anabolic as well as catabolic. These disruptions happen mainly due to inhibitions of enzymes involved in the biochemical processes in metabolic pathways caused by binding with diverse types of exogenous or endogenous pathogenic molecules. Metabolic pathways may also be disrupted due to reasons such as nutritional non-availability of essential molecules and metabolites, scarcity or over expressions of signalling molecules such as hormones and cytokines etc, which are also related with inhitions of related with their genetic expressions.

METABOLIC PATHWAYS

A metabolic pathway is a series of interdependent biochemical reactions controlled by enzymes occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product of one chemical reaction catalyzed by a particular enzyme acts as the substrate for the next. These enzymes often require dietary minerals, vitamins, and other cofactors to function. Side products of these reactions are considered waste, and normally removed from the cell.

Different metabolic pathways take place based on the position within a eukaryotic cell and the significance of the pathway in the given compartment of the cell. For instance, the, metabolic pathways such as electron transport chain, and oxidative phosphorylation etc take place in the mitochondrial membrane. Glycolysis, pentose phosphate pathway, and fatty acid biosynthesis etc occur in the cytosol of a cell.

There are two types of metabolic pathways:

ANABOLIC pathways are characterized by their ability to either synthesize molecules with the utilization of energy.

CATABOLIC pathways are involved with break down of complex molecules by releasing energy in the process.

The two pathways complement each other in that the energy released from one is used up by the other. The degradative process of a catabolic pathway provides the energy required to conduct a biosynthesis of an anabolic pathway. In addition to the two distinct metabolic pathways there is the amphibolic pathway, which can be either catabolic or anabolic based on the need for or the availability of energy.

Metabolic pathways are required for the maintenance of HOMEOSTASIS within an organism, and the flux of metabolites through a pathway is regulated depending on the needs of the cell and the availability of the substrate.

The end product of a metabolic pathway may be used immediately, initiate another metabolic pathway or be stored for later use. The metabolism of a cell consists of an elaborate network of interconnected pathways that enable the synthesis and breakdown of molecules.

Each metabolic pathway consists of a series of biochemical reactions that are connected by their intermediates. The products of one reaction are the substrates for subsequent reactions, and so on. Metabolic pathways are often considered to flow in one direction. Although all chemical reactions are technically reversible, conditions in the cell are often such that it is thermodynamically more favorable for flux to proceed in one direction of a reaction. For example, one pathway may be responsible for the synthesis of a particular amino acid, but the breakdown of that amino acid may occur via a separate and distinct pathway.

Glycolysis was the first metabolic pathway discovered. As glucose enters a cell, it is immediately phosphorylated by ATP to glucose 6-phosphate in the irreversible first step. In times of excess lipid or protein energy sources, certain reactions in the glycolysis pathway may run in reverse to produce glucose 6-phosphate, which is then used for storage as glycogen or starch.

Metabolic pathways are often regulated by feedback inhibition.

Some metabolic pathways flow in a ‘cycle’ wherein each component of the cycle is a substrate for the subsequent reaction in the cycle, such as in the Krebs Cycle.

Anabolic and catabolic pathways in eukaryotes often occur independently of each other, separated either physically by compartmentalization within organelles or separated biochemically by the requirement of different enzymes and co-factors.

A CATABOLIC PATHWAY is a series of reactions that bring about a net release of energy in the form of a high energy phosphate bond formed with the energy carriers adenosine diphosphate (ADP) and guanosine diphosphate (GDP) to produce adenosine triphosphate (ATP) and guanosine triphosphate (GTP), respectively. The net reaction is, therefore, thermodynamically favorable, for it results in a lower free energy for the final products. A catabolic pathway is an exergonic system that produces chemical energy in the form of ATP, GTP, NADH, NADPH, FADH2, etc. from energy containing sources such as carbohydrates, fats, and proteins. The end products are often carbon dioxide, water, and ammonia. Coupled with an endergonic reaction of anabolism, the cell can synthesize new macromolecules using the original precursors of the anabolic pathway. An example of a coupled reaction is the phosphorylation of fructose-6-phosphate to form the intermediate fructose-1,6-bisphosphate by the enzyme phosphofructokinase accompanied by the hydrolysis of ATP in the pathway of glycolysis. The resulting chemical reaction within the metabolic pathway is highly thermodynamically favorable and, as a result, irreversible in the cell.

Cellular respiration is a core set of energy-producing catabolic pathways occuring within all living organisms in some form. These pathways transfer the energy released by breakdown of nutrients into ATP and other small molecules used for energy (e.g. GTP, NADPH, FADH). All cells can perform anaerobic respiration by glycolysis.

Additionally, most organisms can perform more efficient aerobic respiration through the citric acid cycle and oxidative phosphorylation. Additionally plants, algae and cyanobacteria are able to use sunlight to anabolically synthesize compounds from non-living matter by photosynthesis.

In contrast to catabolic pathways, ANABOLIC PATHWAYS require an energy input to construct macromolecules such as polypeptides, nucleic acids, proteins, polysaccharides, and lipids. The isolated reaction of anabolism is unfavorable in a cell. Thus, an input of chemical energy through a coupling with an exergonic reaction is necessary. The coupled reaction of the catabolic pathway affects the thermodynamics of the reaction by lowering the overall activation energy of an anabolic pathway and allowing the reaction to take place. Otherwise, an endergonic reaction is non-spontaneous.

An anabolic pathway is a biosynthetic pathway, meaning that it combines smaller molecules to form larger and more complex ones. An example is the reversed pathway of glycolysis, otherwise known as gluconeogenesis, which occurs in the liver and sometimes in the kidney to maintain proper glucose concentration in the blood and supply the brain and muscle tissues with adequate amount of glucose. Although gluconeogenesis is similar to the reverse pathway of glycolysis, it contains three distinct enzymes from glycolysis that allow the pathway to occur spontaneously.

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