How Environmental Chemicals Destroy Metabolic Processes

A. The "Nuts and Bolts" of a Metabolic Reaction:
e.g.: Glucose  --- Enzyme  ---> Glucose-Phosphate
    Substrate    Enzyme      Product

1. The substrate is the substance which will be modified (ie- Glucose)

2. The product is the result of the converted substrate (ie- Glucose-Phosphate)

3. The enzyme is a biological catalyst which greatly speeds up the conversion of substrate to product. It is over a thousand times larger than the substrates, products, and cofactors, and it is not altered during the reaction. It functions like a workbench or a frame for weaving or needlepoint. Without such a frame to hold the thread in exactly the right position, it is possible to complete the pattern. However, it takes much longer with more errors since the material would be moving around.

4. Cofactors which hold substrates in a specific position which helps the enzyme complete the reaction. They include minerals, vitamins, and other factors.

B. The Metabolic Pathway:
This is a series of metabolic reactions where the product of the preceding reaction acts as the substrate for the subsequent reaction. In the pathways below, substrate "A" is acted upon by enzyme "Ea" to produce "B," "B" is acted on by "Eb" to produce "C," and "C" is acted upon by "Ec" to produce "D," etc. Thus when the product is formed, it is then used as a substrate by the next enzyme.

Major (Usual) path: A -Ea-> B -Eb-> C -Ec1-> D
                         |
Minor (Unusual) path:              --Ec2-> Z

In the major pathway, most of substrate "A" is converted to "D," but a minor amount can be converted to "Z" depending upon the needs of the cell.

A metabolic pathway operates much the same way as do rivers. If the major pathway (river) is unobstructed and flowing easily, most of "A" will be converted to "D." However, if it is dammed up, then run over its banks and form new rivulets. Similarly when the "A to D" pathway is obstructed, then another course will be found such as the minor "A to Z" pathway.

Inhibition of enzymes by their product (ie- "D") are frequent methods by which metabolic processes are regulated. This is most often done by "adjusting" the activity of the enzyme by inhibition in order to yield the amount of product which the cell needs. When product "D" rises to a predetermined level, it inhibits enzyme "Ea" resulting in decreased production of "D." This is called "End-Product Inhibition" and it works like the tank on a bathroom commode -- when the water is low, the inlet valve lets water into the tank, but when the tank is full of water, the valve is shut off. Alternatively, increased production of "Z" can be accomplished either by the inhibition of enzyme "Ec1" or stimulate of enzyme "Ec2."

C. Competitive Inhibition and Regulatory Sites:
The rate of enzyme activity (how fast substrates are converted) is capable of fine degrees of control. This can be done via two different sites on the enzyme- the substrate site and the regulatory site. When a substance with a shape that is similar to substrate "A" binds to the "substrate site" on the enzyme, it blocks the substrate from this site so that the reaction cannot occur. This is like someone parking in your space so you canžt use it. Most drugs act in this way such as serotonin inhibitors, beta blockers, antibiotics, etc.

However, the "regulatory site" is quite different. It may bind a substrate, product, or inhibitor to control enzyme activity. When the regulatory site is bound, it sends a message (by changing the shape of the enzyme) to the substrate site causing it to either speed up or slow down the enzyme activity.

D. 3-Dimensional Shape- the "Lock and Key Fit"
The shape of your car key controls your car-- one notch too many and it wonžt work. Likewise, structural shape is the basis for all chemical reactions, including enzymes, antibodies, substrates, products, toxins, etc. The flat (2-dimensional) shape of a chemical shown in chemistry books is far from the true shape that appears in nature and this difference has caused much confusion in medicine. Hydrocarbons do not look like estrogens on the printed page, and the chemical industry has taken advantage of this to hide the toxic effects of their products. Hormone disrupters are devastating examples of toxins capable of forming shapes which are similar to hormones can block and cause damage to hormone systems.

Cross-reactivity depend solely on shape. If there is a "fit" of a chemical into a site on an enzyme, then that substrate can react with that enzyme. If there is no "fit," then that substrates cannot react with that enzyme, and if there is a partial "fit," then that substrates can partially react by blocking further reactions. This is similar to your Chevy key which can be inserted into other Chevys but cannot turn on the ignition (i.e., partial cross-reactivity). An exact copy of your key would fully cross-react and turn on the ignition but could not even be inserted into a Ford lock.

What is the significance of cross-reactivity? Penicillin-allergic persons should not take any drug similar to penicillin because it may cross-react with penicillin and send them to the emergency room. Drugs such as antibiotics are well studied to give warnings of drug reactions and avoid legal problems. This work came from the bacterial, protein, and chemical cross-reactivities. However a decade ago, the "Lock and Key" theory was confused by the diverse flat structures of the opiate group which had similar effects on the body but also had vastly different flat chemical structures. This was clarified when 3- dimensional techniques were developed to demonstrate that flat chemical structures tell us little about the 3-dimensional structure and that opiates did indeed have shapes similar to the opiate endorphins.

However in spite of these findings, the cross-reactivity of VOCs (volatile organic compounds) with biological substances is still under hot debate, although more for economic than scientific reasons. After 100 years of cross-reactivity data, science and industry still refuse to accept that VOCs can cross-react with biological compounds.

Hormone disrupters have recently become well known when it was found that VOCs can form shapes similar to hormones and thus block hormone receptors. The industry continues to cry "unproven," and to take advantage of the legal notion that the public must prove the toxicity of their chemicals, as opposed to the common sense notion that industry should prove that their products are safe. And this is just the tip of the iceberg.

There are hundreds of diseases that can be caused and/or aggravated by VOCs. Most studies are of "drug interactions" while interactions involving VOCs are largely ignored. It seems that "objective" science sometimes marches forward and sometimes backwards depending upon the leaders!

I appreciate your feedback and criticism.

Contact me at:
Tel 415-677-0829 | Fax 415-677-9745 | E-mail brenn@sfo.com
Lew Brenneman, MD, PhD © 1998

Other articles by Dr. Brenneman, also published in The New Reactor