Tetrahydrobiopterin (BH4) is a multifunctional cofactor required for vital enzyme activity in the synthesis reactions of the neurotrasmitters Dopamine and Serotonin as well as in the synthesis of the gaseous signaling agent Nitric Oxide (NO) involved in vascular health. Through its redox ability is also acts as an intracellular antioxidant free radical scavenger protecting against oxidative stress. BH4 distribution is highly tissue specific and there are regulatory mechanismsto establish BH4 homeostasis which maintains a continuous supply of BH4 at high levels, including intraceller synthesis and recycling. Imbalance entail a drop in BH4 levels with far reaching clinical implications in vascular disease states as seen in high blood sugar, high blood pressure, high blood lipids, elevated homocysteine, diabetes, and atherosclerosis. These share a common pathology of significantly elevated levels of free radical and oxidative stress, both well-known contributors to disease expression and again. The mechanisms differ in how each of these vascular disease states cause significant drops in the levels of BH4 and increasingly detrimental effects are seen when they occur in combination. BH4 rescue, support for ongoing free radical formation, and relief of oxidative stress relative to BH4 is the focus of this paper.
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