When acting as a neurotransmitter NO binds to the iron atom in various heme containing proteins. Is the N or the O atom more likely to be directly attached to the Fe? Explain. Solution Most iron enzymes engage iron either as heme or as a special arrangement of iron with sulphur groups referred to as iron–sulfur centers (FeS) .Iron in heme bears a striking resemblance to magnesium ion in chlorophyll. Heme basically is a porphyrin ring system with iron positioned in the center, is the most common form of iron in biological proteins. In cytochrome c, a common heme protein in the mitochondria, the axial ligands to the iron are occupied by histidine and methionine from the protein. Heme enzymes include calalase and peroxidase. As components of iron–sulphur centers, iron enters into multiple cluster arrangements with cysteine residues on enzymes that offer a more direct contact with the protein. These centers differ in their complexity from the simple 2Fe–2S to the more elaborate 4Fe–4S . Iron in these centers binds substrates as well as transfer electrons and takes part in reactions involving dehydrations and rearrangements. Enzymes with iron–sulphur centers include xanthine oxidase, succinate dehydrogenase, aconitase, and nitrogenase As a neuromodulator or neurotransmitter, NO is released from the synthesis place diffuses through the plasma membranes due to its concentration gradients. NO can directly interact with the cysteinyl side chains of peptides and proteins, iron- containing heme groups, superoxide anion and oxygen. Since the life-span of NO‚ is Only few seconds it is easily inactivated. It has been suggested that some intermediate compounds, for example S-nitrosothiols may act as a carrier system to stabilize, target and to preserve its biological activity. S-nitrosothiols are readily formed from glutathione and NO. Since neurons and glial cells contain GSH at high concentrations, there is a good chance for the reaction to occur. There is indeed evidence that GSNO is synthetized in the CNS. S-nitrosothiols have a wide range of effects: e. g., antimicrobial effect, inhibition of platelet aggregation, bronchodilation and vasodilation..