Nitric oxide, NO, has recently been found to have widespread physiological effects, acting as a major regulator
in the nervous, cardiovascular, and immune systems. The production of NO in the body is regulated by specific
NOS enzymes which exist in at least three different isoforms – bNOS, eNOS, and macNOS. Each of these
isoforms differ in location and function and serve to mediate different physiological responses to NO. Some
physiological roles of NO have been demonstrated as follows:
I. In the central nervous system, NO production is regulated by bNOS. Calcium ion concentrations of 200-400
nM in the central nervous system activate bNOS to catalyze the formation of NO. NO exerts definite effects on
brain function although its specific roles are not well established. bNOS inhibitors have been found to block the
release of neurotransmitter from presynaptic neurons. Excess levels of NO are also thought to contribute to
neurodegenerative disorders such as Alzheimer’s disease.
II. In the blood vessels, NO is produced by eNOS which is activated by Ca2+ concentrations of 200-400 nM. NO
acts as the major endogenous vasodilator in blood vessels. It diffuses into smooth muscle cells and leads to
muscle relaxation by stimulating cGMP formation through activation of guanylyl cyclase. In addition, NO
regulates the vascular system by inhibiting platelet aggregation and adhesion.
III. The role of NO in the immune system is regulated by macNOS through a pathway that is not Ca2+
dependent. Rather, exposure to cytokines, including interleukin-1 and interferon- γ, leads to synthesis of large
amounts of NO by activation of macNOS in response to inflammatory stimuli. The NO produced plays a
definitive role in the mediation of the activities of macrophages and neutrophils. NO also acts to inhibit the
mechanism of viral replication.
A “knock out” mouse with a mutant bNOS protein was generated by recombination techniques. The mutant
protein was identical to the wild-type protein except for the identity of amino acid 675; the mutated bNOS has
Tryptophan instead of Cysteine at position 675. Which of the following is responsible for the mutant protein?
Section: Biological Sciences
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