Anti-Inflammatory Diet

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Anti-Inflammatory Diet and Lifestyle.
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Thursday, September 10, 2009

Watson Makes Us Sick

Common Textbook: Molecular Biology of the Cell, Lacks Coverage of Critical Molecular Interactions

One of the major reasons why healthcare practitioners are unable to cure diseases, is that their molecular view of disease is outdated. Their models of key signaling interactions lack critical molecules and fundamental types of chemical bonds are ignored.

The Major Textbook Used to Train Medical Students Lacks Essential Cellular Interactions

The most pervasive and perhaps the best text book on cell biology, The Molecular Biology of the Cell, first authored by James Watson, lacks a discussion of the bonding of aromatic amino acids (tryptophan, tyrosine, phenylalanine) with basic amino acids (arginine, lysine), carbohydrates, and aromatic phytochemicals, e.g. plant antioxidant or alkaloids. As a result, medical school graduates lack familiarity with the prominent interactions that dominate disease and drug treatments.

Hydrophobic Bonding to Aromatic Amino Acids Dominates Cell Molecular Biology

The dominating significance of aromatic hydrophobic bonds is the strength of these bonds, ca. 20 kcal/mol versus, the commonly considered weak bonds (hydrogen, ionic) at 1-2 kcal/mol, the same as the kinetic energy of water at body temperature. Thus, structures, such as alpha helices and beta sheets of proteins, require multiple weak bonds to be stable, but the hydrophobic bonding of tryptophan to a single arginine draped across its surface is stable.


Tryptophan is the most highly conserved amino acid in protein structures (more than cysteine forming disulfide bonds!). This means that tryptophan is the most important amino acid in protein structure, and probably determines how proteins fold.

Carbohydrates have hydrophobic faces to their ring structures and typically bind to lectins, glycosidases and glycanases, via the hydrophobic surfaces of tryptophans or tyrosines in active sites.

Transport of proteins into nuclei is by binding of arginine or lysine residues of nuclear localization signals (basic quartets or neighboring basic pairs) to tryptophan hydrphobic residues projecting from the surface of LRR (leucine-rich repeat) importin molecules.

Heparin binds to basic amino acids in proteins via hydrophobic interactions. Aromatic dyes, such as berberine, bind to heparin through similar hydrophobic interactions.

Heparin binds to the basic amino acids arrayed in stacks of amyloid molecules and berberine blocks these interactions. Congo Red, a diagnostic dye for amyloids, is an aromatic molecule. Similar interactions occur with prions and the plaques of atherosclerosis.

Acidic polysaccharides form the matrix of biofilms. Heparin and nucleic acids can also serve this function. PEG, which disrupts hydrophobic interactions, can be used to disrupt binding of proteins to heparin, nucleic acids and biofilm polysaccharides.

Heparin binding mediates the interaction between most growth factors or cytokines and their cell surface receptors.

Many viruses and bacteria bind to cell surfaces via heparan sulfate.

LDL binds to LDL receptors via heparan sulfate. ApoE in diagram (arg and lys in blue, hydrophobic in pink.)

Antimicrobial peptides, e.g. defensins, have groups of basic amino acids. Heparin binding domains excised from proteins as peptides are antimicrobial.

Stomach proteases cleave around heparin-binding domains to produce antimicrobial peptides. Intestinal proteases cleave within heparin-binding domains and inactivate bacterial and viral agglutinins.

Life starts with heparin, i.e. heparin is leaked into fertilized eggs to remove the small, highly basic proteins used to package the sperm chromosomes.

Heparin is injected experimentally into nerves to silence IP3 signaling based on the binding of the hydrophobic face of inositol to basic amino acids, similar to heparin binding domains, of the IP3 receptors located on the surface of the ER.

The cytoplasmic domains of some receptor proteins have basic regions that interact with the IPs of the membrane surface, but subsequently serve to transport membrane-derived vesicles to the nucleus via importin carriers.

Heparin/heparan sulfate proteoglycans are secreted bound to basic molecules such as polyamines or histamine.

Heparan sulfate proteoglycans are continually secreted and taken up with a half life of six hours. This circulation is a major transport system of most cells. Amyloid/heparan aggregates on the surface of nerves and gliadin/tTG/antibody/heparan complexes on endocytes (celiac) may poison this system.

All allergens and autoantigens have a triplet of basic amino acids that may be involved in the initial aberrant presentation of these antigens as a result of the internalization by the carbohydrate-binding domain of mannose receptors on the surface of inflammation-stimulated immune cells.

Many neurotransmitters bind to their receptors via hydrophobic, aromatic interactions. These same receptors interact with hydrophobic, aromatic phytochemicals, e.g. “anti-oxidants.” Many spices, herbs, alkaloids and other phytochemicals have their abundantly complex interactions via these mechanisms.

Crystals of the tryptophan repressor involved in binding tryptophan and altering the expression of genes involved in tryptophan synthesis, shatter in the presence of tryptophan -- the tryptophan (yellow) strongly binds to basic amino acids (blue) in the tryptophan-binding domain of each repressor protein in the crystal and alters its shape.


William Trumbower said...

Art WOW! I am an old doc, so I did not even get the stuff you were complaining about. I have learned so much from your posts. In our high risk OB patients we often use heparin therapy. We do not use a dose high enough to anticoagulate the patient, but we seem to get good results. Now I see why.

Nick said...

Hi Art,

Forgive me for going off topic. I just read your post on Vit D and calcium because my girlfriend was told she has osteopenia (age 51). She is very slight. She is going to get her Vitamin D tested, but I'm curious if you have any thoughts on calcium supplementation and what might work best?

Kyle Schneider said...

Hi Art-

Fish oil inquiry here...had no other way to reach you.

I got to the bottom of my bottle of fish oil recently (~10% remaining), and there was a thick residue/substance. This seems to happen with all fish oils I have used. This current bottle was from Carlson Laboratories.

Is this the sign of poor quality fish oil or a normal occurance? I store the oil in the refrigerator, not sure if that makes a difference.

Also, how do you recommend storing to minimize oxidation?

Thanks for all the help,
Kyle Schneider

Dr. Art Ayers said...

It seems like your capsules are rupturing. Maybe they are freezing.
It is probably no big deal. I store mine at room temp.
I don't worry about my fish oil oxidizing, since my wife and I both use a fair number of capsule and go through a bottle quickly. We assume that the turnover will avoid any problems. For good or ill, I don't tend to worry about such things.
I wrote a whole post on not sweating the small points.

Thanks for the comments.

Anna said...

I assumed Kyle was referring to a bottle of bulk fish oil, not fish oil in capsules. I have noticed the same residue at the bottom of the bottle (not in capsules) & in Cod Liver Oil in the past, so I shake the bottle of fish oil each time I pour a dose.

We're currently using Sonne's Norwegian CLO right now (traditional with naturally occurring vitamins) and Green Pastures Fermented Skate Liver oil. I have a bottle of Nordic Natural bulk fish oil but it isn't opened yet.

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