Binding

The molecular connections that take place in the brain are similar to all other bindings.

Enzyme and substrate, hormone and hormone receptor, neurotransmitter and its synapse, all function as receptor and ligand or the binding of molecular mates.

 

Receptors and their ligands are the molecular, locks and keys that allow the brain to regulate the entire body.

 

The locks have a high specificity of binding, with even a slight alteration in either lock or key, destroying the relationship.

This binding phenomena is based on a perfect spatial fitting between a drug or hormone, and a receptor.

The receptor-ligand or hormone-hormone receptor complex, signals the cell to turn on and off specific functions.

 

The difference between receptors centers on the small region known as the binding domain.

This binding area determines which hormone can bind to the domain and which ones can’t.

 

Hormones can’t bind with damaged receptors and results in disease.  

 

Nutritional diabetes otherwise known as adult onset or Type II diabetes, is caused by insulin receptors losing their selectivity.

Receptor binding domains are coded for by a section of DNA or gene. Different genes code for different receptors.

Receptor binding domains have been cloned, and the DNA sequences that code for them.

Synthesizing and collecting them creates a combinatorial receptor library. Ligands are then ‘tested’ to see what receptors bind it binds to,

Artificial combinatorial receptors libraries are used to test a vast array of ligands. These libraries and their artificial receptors are used to discover new drugs and applications for old ones.

Artificial receptor libraries are powerful tools to identify ligands, and pathogenic organism.

These libraries are used to counter bioterrorism and speed development of anti-cancer and anti-viral drugs

Receptors are found embedded in cell and nuclear membranes, antibodies, in synapses and on molecules of cholesterol.

The number and diversity of receptors found in any given cell is a reflection of the type of activity carried out by the cell. The number of receptors is greatly exceeded by the number of potential ligands. These ligands include all of Nature’s libraries.

Many natural receptors that have been cloned do not bind with any of the usual ligands (hormones, drugs and neurotransmitters). These are called orphan receptors. Orphan receptors probably bind with a steroid-receptor complex.

Steroids exert their effect by passing through the outer membrane, binding with a carrier receptor and entering the nucleus.

In the nucleus, the steroid-complex can either interact directly with DNA to activate the involved genes or the steroid can rebind with a nuclear receptor, which interacts with DNA..

If the binding with DNA increases transcription its called a promoter. If the absence of the hormone receptor complex represses translation, it’s called a repressor.

Transcription is the creation of a messenger RNA that serves as the blueprint for translating amino acids into the desired protein.

Promoters and repressors are based in the presence or absence of a ligand (the steroid) binding with a carrier, creating a new ligand (the complex).

Promoters and repressors turn on and off the transcription of a gene.

Mutators alter the genetic code by initiating a response to the assortment of chemicals, free radicals and uv light the cells’s nucleus is exposed to.

Nuclear Receptors

When typical membrane surface receptors become bound, they signal a series of reactions. This is called a G-protein coupled receptors. Their activation signal is amplified by the coupled second messenger. Steroid hormones do not act via this second messenger mechanism but rather interacts directly with DNA.

Nuclear receptors regulate the processes of homeostasis, reproduction and metabolism. Nuclear hormone receptors function as ligand activated transcription factors.

When bound nuclear receptors promote DNA transcription.

These factors link the signalling molecules (hormones) that control these processes to a responses that results in protein synthesis via translation.

These receptors bind with an assortment of hydrophobic ligands. These include the lipid soluble steroid hormones (estrogens, glucocorticoids, mineralcorticoids and androgens).

Other hydrophobic ligands that bind with nuclear receptors include vitamin D, thyroid hormones, fatty acids, leukotrienes and prostaglandins.

Nuclear receptors that have no identified natural ligand are called nuclear orphan receptors. The search for ligands that can bind with orphan receptors is the subject of intense research.

The sequence of nucleic bases or DNA sequences that code for the proteins that make up the binding domain of receptors are all compiled in a database. The use of this data constitutes the science of bioinformatics.

Bioinformatics or computational biology is the study of this information. It is used to help design drugs and novel experiments.

Biological receptors bind to their targets via a lock and key mechanism.  This interaction utilizes a sophisticated molecular recognition system based on spatial fitting.

Receptors include cell membrane bound proteins,  antibodies, nuclear membrane receptors, enzymes and ribozymes.  They are found in muscle cells, nerve cells, eggs and sperm cells, T-cells as well as viruses, and bacteria.

The chemistry  and language of receptor biology is very complicated.  The Athlete’s Diet eliminates much of the chemistry and stresses the importance of visualizing the receptor as a protein whose purpose is to bind with one specific ligand. The consequence of that binding causes the effect of the ligand.

The structural similarity of steroids and plant saponins,  neurotransmitters and alkaloids, alcohol and GABA receptors or opiates and endorphin receptors allows these ligands to produce their effects.

Human life itself is the result of the bonding of a spermatoid with an ovum.

It is the structural similarity of ligands, not their chemistry that permits binding.

Conventional science when I attended school stressed chemistry over structure. This forced students to memorize insignificant details to predict chemical behavior.

Advances in combinatorial chemistry eliminated that need. There are now libraries of molecules that contain, at least with the aid of a combinatorial algorithms and bioinformatics, all possible combinations or universe of isoforms.

Evolution

The human genome continues to evolve. This active and living blueprint continues to adapt to any change in its environment or in response to whatever ligands it is exposed to.

Drugs, food, light, sound, hormones, antibodies, viruses, neurotransmitters, prostanoids, acupuncture and placebo all involve a receptor to a ligand binding, the 0 and 1’s of Nature. Each ligand has a specific receptor that it binds with.

Genomic mapping reveals that all steroid receptors probably  evolved from one ancient or prototype receptor.

Their evolution occurred in two waves of genomic mutations. One set of mutations took place before the appearance of jawed vertebrates and one after.

Cortisol, a glucocorticoid hormone and aldosterone, one of the mineralcorticoids, had receptors that go back to a common ancestor some 450 million years ago. Cortisol doesn't not bind with aldosterone receptor and vice versa.

It is believed that cortisol and therefore the glucocorticoid receptor existed in the pre-jawed species but aldosterone and the mineralcorticoid receptor did not.

How then can the primordial receptor bind with both hormones? If aldosterone didn’t exist until ten of millions of years later, how could a receptor be formed to bind with it?

Is there a receptor on demand service that codes for proteins  on-the-fly?  Or a receptor manager gene that modifies the proteins it codes for, based on the presence of an unrecognized ligand? Are receptors formed in anticipation of a response or after exposure to a ligand?

Research on the two steroids have determined that mutations on the genes that code for receptors created new receptors that were able to bind with an alternate compound.

Science has based its theory of evolution on the concept of random mutations. The overwhelming number of which, have benefited today’s surviving species. Those species, whose mutations net effect was to harm their prospects for survival, are no longer with us. Those individuals within the species who developed harmful mutations become damaged and die prematurely.  Mutations within individuals that are beneficial makes one more resistant to disease.

Gene mutations are linked to events. Radiation, drugs,  foods, additives, initiate these changes, I call them Mutators.

The DNA code responds to promoters and repressors by increasing or decreasing production of specific proteins but what about Mutators, what effects do they produce?

A mutator can bind with the original prototype receptor and form a mutator-receptor complex. This then interact directly with DNA causing the formation of new receptors.  Unlike the original receptor that was capable of binding with a number of similarly structured compounds, the new receptor can only bind to its predetermined ligand.

This demonstrates how Nature provided the ability to create receptors without ever having been exposed to it.change the code into one that has the new binding domain. The next generation of receptors will thus only be  able to recognize and bind to the specific mutator. In the case of antibodies, this is a positive mutation because it helps rid the body of the offending agent.

If it results in receptors that can no longer recognize its normal ligand, it is a negative mutation and leads to disease. If the receptor-mutator complex results in too many receptors, it produces addiction.

Intelligent Design

The theory that the universe and all living things are the result of a directed, intelligent cause is known as intelligent design (ID).

ID is creationism in scientific clothing. That is unfortunate because, there are some good arguments on how life might follow a design, their failure is in requiring that there be a designer. Id intentionally avoids identifying the intelligent force.

ID rejects all concepts of evolution and its mechanism of natural selection. ID’s proponents argue that it is a scientific theory that best explains life. Its the watchmaker analogy on steroids.

The belief in an all powerful, supernatural force is as old as humankind. ID assumes not only the the existence of a designer but also a mover of that force. ID hides it roots by shielding them with scientific terms like specified and irreducible complexities.  As if by saying science, it becomes so.

ID  states that the universe and life cannot be attributed to chance. But that is a question of faith, not science. ID’s mistake is in trying to answer questions of faith with the reasoning of science.

Evolution does not require the absence of a god. An all powerful force can still operate on chance without diminishing its power. Just as people of faith can still believe in science without abandoning their god.

The Athlete’s Diet has presented advanced molecular biology in the previous pages. This state of the art science and forms the core of its theory on health and how best to maintain it.

The remainder of the book treats exercise and food, the nuts and bolts of nutrition science, as tools to prevent disease.

Since foods function like drugs, this book recommends the most beneficial ones and provides the rationale behind their choice. It is always based on their ability to fuel exercise and aid the body’s recovery from it.

While the science may prove challenging for non-scientists, it isn’t string theory.  For athletes, the language of biology is far easier to understand than the language of math.

The molecular mechanism of botanicals is similar to drugs. Receptor-ligand binding. In the case of botanical, the number of ligands present, reflects the complexity of plants.

Plants contain multiple versions of the same ligand. I call it  Nature’s library. As a library of compounds, they bind with more than one type receptor. This modifies the effect and makes the botanical less powerful and more safe.

The Athlete’s Diet rejects the chronic use of pharmaceutical drugs and decribes addictions as manifestation of altered receptor binding in nerve tissue. These addictions to narcotics, painkillers, tranquilizers, fats, sweets, cigarettes, sleeping pills, muscle relaxants, exercise, coffee, mood transmitters, marijuana and alcohol all cause their addiction by the phenomona entitiled receptor recruitment.

It is also a natural method to improve performance and prevent injury. It therfore rejects the use of steroids, designer drugs and controlled substance analogs. These are abused, not  addictive drugs. This does not mimimize their danger.