Question 2 - Inosine in AMP catabolism
Introduction
Adenosine monophosphate (from now on referred to as AMP) is the lowest energy-containing nucleotide found in living organisms. In its degradation process (Figure 1), several enzymes and intermediates are required, playing important roles that regulate the correct functioning of the overall process. An alteration in any of those participants can cause severe consequences, such as immunosuppression. Inosine is one of those previously mentioned intermediates, formed in the first step of the AMP catabolism by the action of an enzyme known as adenosine deaminase (1).
Discussion o Why a blockade in its formation leads to severe immunosuppression?
Inosine, as it has been already mentioned,
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They are classified as nNOS, which is found in neuronal tissue, the inducible isoform iNOS, located in macrophages, and eNOS, mostly found in endothelia (2).
The neuronal isoform nNOS is present in central and peripheral neuronal cells and is involved in the development of nervous system, as they produce the necessary physiological concentrations of NO needed in cellular communication. nNOS has many other physiological functions, including regulation of cardiac function and peristalsis, sexual function, contraction of skeletal muscle or body fluid homeostasis. nNOS in the heart protects against cardiac arrhythmia induced by myocardial infarction. This isoform, as well as eNOS, is Ca2+ dependent (3), (4).
The inducible isoform produces large amounts of NO as a defense mechanism, affecting tumoral or infected cells. Moreover, as the induction of the isoform takes place in an oxidative environment, high levels of NO react with O2, forming superoxide anions that kill macrophages and the infectious particles they contain (3). High concentrations of NO can produce interferences in DNA, breaking and fragmenting it. The activation of this isoform does not depend on Ca2+/calmodulin, but is induced in presence of inflammatory cytokines