Just say NO to muscle growth!

The signaling molecule nitric oxide (NO), made up of one nitrogen atom and one oxygen atom, has become a popular compound in the weightlifter’s arsenal for increased muscle growth. NO is biosynthesized from the amino acid L-arginine and oxygen by the enzyme nitric oxide synthase (NOS), therefore supplementation with the amino acid L-arginine could increase NO production. (Fig 1 shows the reaction mechanism of NOS). NO has many roles but the one athlete’s desire is increased blood flow caused by vasodilation. Vasodilation occurs when NO binds guanlyl cyclase’s heme moiety triggering conformational changes within the heme and protein that generate a fully active guanlyl cyclase (Fig. 2 illustrates the guanlyl cyclase heme group, highlighted by the green arrow, bound to NO, depicted by the blue arrow, with the heme’s axial ligand histidine, emphasized by the red arrow, just before the histidine residue dissociates from the heme initiating further conformational change of the heme group and protein molecule). The activated guanlyl cyclase catalyzes the conversion of GTP to cyclic GMP. Cyclic GMP then activates protein kinase G (PKG), which subsequently leads to myosin light chain dephosphorylation, smooth muscle relaxation, and vasodilation within the arterial wall (Fig. 3 depicts NO’s role during arterial vasodilation) generating increased blood flow. Greater blood flow brings more essential nutrients and oxygen to laboring muscles stimulating recovery and growth of the muscle tissue.
Nitric oxide is a highly reactive and transient signaling molecule. For NO to function non-locally in the human body it is transported via protein molecules. Intriguingly during physical exertion, as vasodilation increases blood flow to working muscles it increases muscle concentration of red blood cells and hemoglobin, the protein abundantly found in red blood cells. This hemoglobin may be post-translationally modified with NO attached to the sulfur atom from the amino acid cysteine (Fig. 4 shows the electron density map around the NO modified cysteine residue in hemoglobin), essentially increasing the local arterial concentration of NO after it dissociates from the hemoglobin molecule proliferating vasodilation. Furthermore, NO modified hemoglobin has an altered affinity for oxygen and carbon dioxide producing a more efficient exchange of oxygen for carbon dioxide in hypoxic working muscles. This NO modification generates additional vasodilation and superior oxygen replenishment promoting all of the benefits of increased blood flow for working muscles and the avid weightlifter.