Re: Detoxifying acetaldahyde

A healthy body needs healthy cells and the health of each and every individual cell depends upon what is happening within and without at the biochemical level. Aerobic organisms, which derive their energy from the reduction of oxygen, play a dangerous game if they are unable to deal with the small amounts of superoxide anion (•O2-), hydroxyl radical (•OH) , and hydrogen peroxide (H2O2) that arise during the electron ping-pong performed by mitochondria. A closer look at this area of reactive oxygen species (ROS) is warranted in relation to aldehydes.

The hydroxyl radical is the most reactive of these species. It likes to swipe hydrogen atoms from polyunsaturated fatty acids (the initiation step) to return to a stable state as a water molecule:



The purloined hydrogen atom leaves the lipid with a carbon-centered unpaired electron that can attract molecular oxygen in the peroxidation (oxygen uptake) step forming a lipid peroxide:



But this configuration is still unstable and the lipid peroxyl radical can second another hydrogen atom from another lipid in the propagation step forming a lipid hydroperoxide:



Although not a radical species, this configuration is conformationally unstable and can split the lipid into another lipid radical, a lipid fragment and aldehydes such as malondialdehyde:



If acetaldehyde is a dagger with a highly reactive carbonyl group that can damage body tissue, DNA, enzymes, and other chemical compounds; then malondialdehyde is twice as deadly with two carbonyls in a tiny molecule. This double-edged sword has no beneficial aspect. Whereas acetaldehyde can latch onto things and slice things and change them into something else, malondialdehyde can not only do this but also cross-link structures creating tangles and log jams that are beyond rescue. The detectable levels of malondialdehyde in a cell are a measure of oxidative stress [1].

Since the pathway to malondialdehyde described produces spinoff radical species along the way, each of these can initiate another similar pathway resulting in a chain reaction that can rapidly get out of control. If the cellular redox pools and enzymes responsible for maintaining order amidst the chaos cannot intercept the ROS and quench the deleterious cascade, the cell must consider more drastic measures to ensure that its insanity doesn't spread.

Apoptosis is the rapid disintegration of a cell into bite-sized chunks that can be assimilated and disposed of by macrophages -- a form of self-programmed cellular suicide. Death of a cell by trauma (necrosis) can spill harmful contents (such as reactive aldehydes) into the extracellular environment. Apoptosis, on the other hand, produces encapsulated cell fragments that phagocytic cells are able to engulf and quickly remove before the contents of the cell can cause damage to surrounding cells. More than 50 billion cells per day may undergo apoptosis in an average human adult with higher rates in individuals with degenerative diseases associated with oxidative stress [2].

[1] Valenzuela A, "The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress." Life Sci. 1991;48(4):301-9.
http://www.ncbi.nlm.nih.gov/pubmed/1990230

[2] "Malondialdehyde + Disease", From: Davis AP et al., "The Comparative Toxicogenomics Database: update 2011.", Nucleic Acids Res. 2011 Jan;39(Database issue):D1067-72. Epub 2010 Sep 22.
http://ctdbase.org/detail.go?view=disease&type=chem&acc=D008315
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