Some Things Aren't Directly Toxic To Us, But It's Their Metabolites That Are.

Or rather, what does the body do to them biologically to turn them toxic?

It’s not necessarily the case that the chemicals we come into contact with are directly harmful to our bodies. What we do need to understand is the clear difference between the chemical activity and the biochemical activity of any given chemical.

The chemical activity of a substance refers to the chemical reactions that it can undertake. These are governed by the laws of physical, inorganic and/or organic chemistry.

An aldehyde, for instance, will react with an amine to form an imine. That’s the basis of a higher HbA1c reading that diabetics will experience, and that reaction is governed by the laws of organic chemistry.

A biochemical activity is more tricky to gauge. There are so many different types of enzymes and biological receptors in our body, and these enzymes are able to catalyse reactions that organic chemistry would deem as next to impossible.

For example, the epoxidation of a polycyclic aromatic hydrocarbon (PAH) doesn’t occur readily under ambient conditions. However, the cytochrome P450 monooxygenase enzymes can very readily carry out the epoxidation reaction under ambient conditions.

Our body contains many of these cytochrome P450 enzymes, and as a result we can take a relatively unreactive PAH molecule (which we can get from charred foods) and turn it into something that is potentially carcinogenic, because these epoxides can react with cellular DNA to form adducts, which the layman will otherwise know to be a DNA mutation.

Another consideration would be that of the difference between methanol and ethanol. Chemically, they look relatively similar - methanol (CH3OH) and ethanol (CH3CH2OH) differ by just an extra -CH2 group in ethanol.

A -CH2 group on its own is also remarkably unreactive.

However, when we look at the biochemical metabolism of ethanol in the body, we’d see that the alcohol dehydrogenase (ADH) enzyme in the liver oxidises it into acetaldehyde, and the acetaldehyde dehydrogenase (ALDH) enzyme further oxidises it into acetic acid (vinegar).

Alcohol oxidation otherwise proceeds relatively slowly under ambient conditions. It takes quite a while for a bottle of freshly opened wine to go sour from the oxidation of ethanol into vinegar. This rate of reaction is dependent on the laws of physical chemistry.

But the ADH and ALDH enzymes can metabolise the ethanol into acetic acid pretty quickly, and we’d be peeing it out within 24 hours.

The problem is that ADH and ALDH will also very readily oxidise methanol - firstly into formaldehyde (ADH), and then next into formic acid (ALDH).

Unfortunately, while acetic acid does not biochemically affect the activity of mitochondrial cytochrome oxidase enzymes, formic acid does. It is stated that:

Formic acid has been demonstrated in vitro to induce mammalian cell death by inhibiting the activity of cytochrome oxidase, the terminal electron acceptor of the electron transport chain that is involved in ATP synthesis, resulting in depletion of ATP and subsequent cell death due to reduction of energy levels so that essential cell functions cannot be maintained.

The electron transport chain is responsible for transporting electrons during the energy generation process in the cell to produce adenosine triphosphate (ATP). When a cell is unable to produce ATP, it’s not going to have any juice to power itself, so to say.

And the cell finally dies, prematurely.

High-energy organs such as the heart and the brain can be significantly affected by this formic acid inhibition, and people may die from formic acid poisoning as such.

However, ADH does have a higher affinity for ethanol than methanol.

Hence, if one does accidentally consume methanol, the trick would be to feed them more ethanol. The ethanol gets preferentially oxidised into harmless vinegar while blocking out methanol from getting oxidised into the toxic formic acid.

Coupled with haemodialysis, it would be much easier to eliminate all that excess methanol from the blood before it starts to kill someone.

And there’s the difference between chemical and biochemical activity.

Sometimes we just don’t know what the enzymes in our body can do.

As such, there’s always a concern about the side effects that new drugs can cause in the human body - because their ability to unlock receptors that they weren’t designed to target could potentially be fatal!

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