Date Published: 19 September 2011

Adaptation of haemproteins to protect against carbon monoxide produced within the body

How do living organisms control production of carbon monoxide within their tissues so that it is not harmful ?

Carbon monoxide (chemical symbol CO) is well known to be a toxic gas that can be fatal at high concentrations. Carbon monoxide is the gas is most commonly associated with faulty domestic heating systems and car fumes, hence the popularity of carbon monoxide detectors in homes and workplaces.

It is probably less well-known that carbon monoxide is also produced within living tissues, including those in the human body, through the normal activity of biological cells. The question of how organisms such as the human body control production of internal carbon monoxide so that it is not harmful has puzzled scientists for a long time. The answer to this question has recently been found by researchers at Liverpool University (England, UK) working together with colleagues based in Manchester (England) and Oregon (USA) who have discovered the mechanism by which the cells of living organisms protect themselves from the toxic effects of the gas at these lower concentrations

Carbon monoxide molecules should be able to readily bind with protein molecules found in blood cells, known as haemproteins. When they do, e.g. when there is a high concentration of carbon monoxide in the lungs and tissues due to intake of breath when there is a high concentration of carbon monoxide in the air, the carbon monoxide molecules impair normal cellular functions, such as oxygen transportation, cell signaling and energy conversion. In extreme cases this can lead to death by carbon monoxide poisoning.

The haemproteins provide an ideal 'fit' for the CO molecules, like a hand fitting a glove, so the natural production of the gas, even at low concentrations, should in theory bind to the haemproteins and poison the organism, except it doesn't.

Professor Samar Hasnain, of Liverpool University's Institute of Integrative Biology, said:

" Toxic carbon monoxide is generated naturally by chemical metabolic reactions in cells but we have shown how organisms avoid poisoning by these low concentrations of 'natural' carbon monoxide.
_ Our work identifies a mechanism by which haemproteins are protected from carbon monoxide poisoning at low, physiological concentrations of the gas. Working with a simple, bacterial haemprotein, we were able to show that when the haemprotein 'senses' the toxic gas is being produced within the cell, it changes its structure through a burst of energy and the carbon monoxide molecule struggles to bind with it at these low concentrations.
_ This mechanism of linking the CO binding process to a highly unfavourable energetic change in the haemprotein's structure provides an elegant means by which organisms avoid being poisoned by carbon monoxide derived from natural metabolic processes. Similar mechanisms of coupling the energetic structural change with gas release may have broad implications for the functioning of a wide variety of haemprotein systems. Haemproteins, for example, bind other gas molecules, including oxygen and nitric oxide. Binding of these gases to haemproteins is important in the natural functions of the cell." [bold added by IvyRose Ed.]

Dr Svetlana Antonyuk, also based at the Institute of Integrative Biology, said:

" We were surprised to discover that haemproteins could have a simple mechanism involving unfavourable energetic changes in structure to prevent carbon monoxide binding. Without this structural change carbon monoxide would bind to the haemoprotein almost a million times more tightly, which would prevent the natural cellular function of the haemprotein and any organism to survive."

This research might eventually lead to development or improvement of the use of haem-based sensors for gas sensing in a wide range of biotechnological applications. For example, there may be a possibility of and application for sensors for use to monitor gas concentrations in industrial manufacturing processes or biomedical gas sensors, where accurate control of gas concentration is critical.

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