Why does cyanide kill? Fermi paradox revisited.
Cyanide kills because it binds to metal ions, inactivating critical iron-containing metalloenzymes, such cytochrome c oxidase and methemglobin. The former is a respiratory enzyme; the same enzyme is inactivated by azides, H2S, CO, and methanol. Why do we have such vulnerability? The problem here is that some eukaryotes have alternative oxidases (AOX)
http://en.wikipedia.org/wiki/Alternative_oxidase
that are not inhibited by the cyanide. This alternative respiration pathway exists in plants, fungi, amoebae, and some other protists; yet only in one species - a protozoan that causes sleeping disease - AOX completely replaces the cytrochrome pathway. All of these AOXs are bacterial in origin, just like our own mitochondria. There are a lot of plants, animals, and bacteria making cyanide. Rarely is this cyanide used to kill
http://www.ncbi.nlm.nih.gov/pubmed/11591663
More commonly it is used for signalling or alternative biochemistry; plants use it as repellants for their grazers. Some tolerance is expected in these cyanogenic organisms, but only to low concentration of cyanide they produce themselves. However, there are bacteria that can live on nothing but concentrated cyanide!
...A bacterial strain able to use cyanide as the sole nitrogen source under alkaline conditions has been isolated. The bacterium was classified as Pseudomonas pseudoalcaligenes. Cyanide consumption is an assimilative process, since (i) bacterial growth was concomitant and proportional to cyanide degradation and (ii) the bacterium stoichiometrically converted cyanide into ammonium. The bacterium was able to grow in alkaline media, up to an initial pH of 11.5, and tolerated free cyanide in concentrations of up to 30 mM. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC546731/
...Cyanide is highly toxic to living systems because it forms very stable complexes with transition metals that are essential for protein function. In spite of its extreme toxicity, some organisms have acquired mechanisms to avoid cyanide poisoning. The biological assimilation of cyanide needs the concurrence of three separate processes: (i) a cyanide-insensitive respiratory chain, (ii) a system for iron acquisition (siderophores) and (iii) a cyanide assimilation pathway. Siderophores are low-molecular-mass compounds (600-1500 Da) that scavenge Fe(III) ions (usually with extremely high affinity) from the environment under iron-limiting conditions. There are two main classes of siderophores: catechol and hydroxamate types. In the presence of cyanide, bacterial proliferation requires this specific metal uptake system because siderophores are able to break down cyano-metal complexes. http://www.ncbi.nlm.nih.gov/pubmed/16417508
These bacteria have solved two related problems of cyanide poisoning: they use AOX to protect their respiratory chain, and they can wrestle iron from the cyanide complexes using their siderophores. They also worked out how to convert cyanide into nontoxic chemicals, but that is a minor problem. So there is nothing in biochemistry that makes the cyanide inherently more poisonous than, say, oxygen - if you know how to handle it. The reason we are not cyanide-resistant is that we are not exposed to the cyanide normally, so we've lost the cyanide-tolerant metabolic pathways.
The interesting thing is that the cyanide was common in the distant anoxic past when the Earth was young, before the oceans and the atmosphere were oxygenated by cyanobacteria. HCN and other cyanides (HC3N, cyanogen) are the major components of reductive atmospheres containing nitrogen, e.g. Titan's atmosphere. If there are hydrocarbons and nitrogen, it is inevitable than the cyanide is produced via stratospheric photochemistry and/or electric discharges. The HCN combines with ammonia and other organics to make N-heterocycles, so it is an important stepping stone towards nucleobases. The terrestrial oceans were literally loaded with the cyanide, and life was originally tolerant of this cyanide and perhaps dependent on it. Only when the oxygenation occurred had the life gradually became intolerant of the cyanide, with a few species still having a toehold in the old world.
Given that O2-evolving photosynthesis cannot work on most planets with anoxic atmospheres (the organic haze would be too thick to transmit visible light to the ground), it is likely that alien organic life would be highly tolerant of cyanide but highly intolerant of oxygen.
So it is not surprising that no one likes us. If we want to be visited by aliens we should make this planet more habitable, removing oxygen from the air and converting nitrogen to the cyanide. It is like living on a planet covered with hydrofluoric acid and wondering why no one comes to play... such a great paradox indeed.
http://en.wikipedia.org/wiki/Alternative_oxidase
that are not inhibited by the cyanide. This alternative respiration pathway exists in plants, fungi, amoebae, and some other protists; yet only in one species - a protozoan that causes sleeping disease - AOX completely replaces the cytrochrome pathway. All of these AOXs are bacterial in origin, just like our own mitochondria. There are a lot of plants, animals, and bacteria making cyanide. Rarely is this cyanide used to kill
http://www.ncbi.nlm.nih.gov/pubmed/11591663
More commonly it is used for signalling or alternative biochemistry; plants use it as repellants for their grazers. Some tolerance is expected in these cyanogenic organisms, but only to low concentration of cyanide they produce themselves. However, there are bacteria that can live on nothing but concentrated cyanide!
...A bacterial strain able to use cyanide as the sole nitrogen source under alkaline conditions has been isolated. The bacterium was classified as Pseudomonas pseudoalcaligenes. Cyanide consumption is an assimilative process, since (i) bacterial growth was concomitant and proportional to cyanide degradation and (ii) the bacterium stoichiometrically converted cyanide into ammonium. The bacterium was able to grow in alkaline media, up to an initial pH of 11.5, and tolerated free cyanide in concentrations of up to 30 mM. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC546731/
...Cyanide is highly toxic to living systems because it forms very stable complexes with transition metals that are essential for protein function. In spite of its extreme toxicity, some organisms have acquired mechanisms to avoid cyanide poisoning. The biological assimilation of cyanide needs the concurrence of three separate processes: (i) a cyanide-insensitive respiratory chain, (ii) a system for iron acquisition (siderophores) and (iii) a cyanide assimilation pathway. Siderophores are low-molecular-mass compounds (600-1500 Da) that scavenge Fe(III) ions (usually with extremely high affinity) from the environment under iron-limiting conditions. There are two main classes of siderophores: catechol and hydroxamate types. In the presence of cyanide, bacterial proliferation requires this specific metal uptake system because siderophores are able to break down cyano-metal complexes. http://www.ncbi.nlm.nih.gov/pubmed/16417508
These bacteria have solved two related problems of cyanide poisoning: they use AOX to protect their respiratory chain, and they can wrestle iron from the cyanide complexes using their siderophores. They also worked out how to convert cyanide into nontoxic chemicals, but that is a minor problem. So there is nothing in biochemistry that makes the cyanide inherently more poisonous than, say, oxygen - if you know how to handle it. The reason we are not cyanide-resistant is that we are not exposed to the cyanide normally, so we've lost the cyanide-tolerant metabolic pathways.
The interesting thing is that the cyanide was common in the distant anoxic past when the Earth was young, before the oceans and the atmosphere were oxygenated by cyanobacteria. HCN and other cyanides (HC3N, cyanogen) are the major components of reductive atmospheres containing nitrogen, e.g. Titan's atmosphere. If there are hydrocarbons and nitrogen, it is inevitable than the cyanide is produced via stratospheric photochemistry and/or electric discharges. The HCN combines with ammonia and other organics to make N-heterocycles, so it is an important stepping stone towards nucleobases. The terrestrial oceans were literally loaded with the cyanide, and life was originally tolerant of this cyanide and perhaps dependent on it. Only when the oxygenation occurred had the life gradually became intolerant of the cyanide, with a few species still having a toehold in the old world.
Given that O2-evolving photosynthesis cannot work on most planets with anoxic atmospheres (the organic haze would be too thick to transmit visible light to the ground), it is likely that alien organic life would be highly tolerant of cyanide but highly intolerant of oxygen.
So it is not surprising that no one likes us. If we want to be visited by aliens we should make this planet more habitable, removing oxygen from the air and converting nitrogen to the cyanide. It is like living on a planet covered with hydrofluoric acid and wondering why no one comes to play... such a great paradox indeed.