NO is a Janus molecule, since depending on its intracellular concentration, it may act as a physiological signaling molecule or as a toxic agent. This is also applicable to its reactions with the respiratory chain, which may be physiologically modulated at relatively low NO mitochondrial fluxes, but severely affected by higher, toxic concentrations. It is known that NO inhibition of mitochondrial respiration has a role in cell death, by either necrotic or apoptotic mechanisms. Moreover, NO toxicity in the extreme is mediated by the reactive peroxinitrite species (ONOO−), formed by the reaction of NO with the superoxide anion; unlike NO, peroxinitrite is indeed causing an irreversible inactivation of respiration. A strict control of intracellular NO may therefore be welcome by the cell.

NO is induced on surface with UV light exposure..........UV light is only present certain times of the day and it is also released by cells under some stress. Since NO slows ECT it can limit apoptotic damage that leads to tissue atrophy.......if we have no NO we see diseases where tissue atrophy occurs: AMD, Alzheimers, Parkinson's disease are some examples of diseases with losses of tissue density in places.

 

• S. Moncada, J.D. Erusalimsky
• Does nitric oxide modulate mitochondrial energy generation and apoptosis?
  
  
• Nat. Rev., Mol. Cell Biol., 3 (2002), pp. 214–220
  

 

• G.C. Brown, V. Borutaité
• Nitric oxide inhibition of mitochondrial respiration and its role in cell death
  
  
• Free Radic. Biol. Med., 33 (2002), pp. 1440–1450
  

 

Regardless of the detailed NO• binding mechanism to cytochrome C heme protein, science cannot explain why in CBS, CO preferentially binds to the cysteine side, whereas NO• seems to bind to the histidine side. My answer is tied to how UV light interacts with aromatic amino acids. tyrosine has side chains that are photoelectrically excited by UV light to separate S-S bonds. This makes H2S free radical which likely guides the reaction sites. Despite the lack of an unequivocal explanation for this, it should be pointed out that, at equilibrium, binding of NO• and CO on opposite sides of the heme is not unprecedented, having been reported for bacterial cytochrome c. This would make sense because bacterial do not use UV light the same way eukaryotes do because of a lack of DHA in their cell membranes

 

Why might things be built this way? Sunlight normally stimulates NO release. This occurs on short timescales to vasodilate surface vessels to get UV light to bind to porphyrins and hemoglobin bonds oxygen. It turns out oxy Hb turns off NO flux. It limits NO affect on cytochrome c.

So why might we be built this way? To deliver oxygen to tissues that dont have a ton of mitochondria and/or blood flow/ and or light exposure. Consider under normal metabolic conditions, a considerable fraction of Cox oxidase (cyto C) is inhibited.....what would this do? It would have the effect of extending O2 availability either to cells at different distances from capillaries, or even within the mitochondrion, allowing O2 utilization by as many as possible respiratory enzyme complexes, differently distributed in space within the organelle. This would limit pseudohypoxia............Remember that oxygen is drawn to things naturally that are magnetic because O2 is paramagnetic.

 

This helps explain how UV light exposure can stimulate venous O2 increase within cells.........heretofore medicine does not know this is possible........but this is the detailed mechanism of how it can happen.