Enzymatic Systems for the Reduction of Hemoglobins in Animals and Humans

— The review discusses the enzymatic reduction systems that maintain animal heme-containing globins in a physiologically active state. There are two types of reductases. Specialized systems (two-component: cytochrome-b5 reductase/cytochrome b5) provide rapid reduction of hemoglobin (Hb) and myoglobin (Mb), which is important for oxygen transport and storage. The main enzyme, CYB5R3, reduces Hb, Mb, and presumably cytoglobin (Cygb) and neuroglobin (Ngb). CYB5R4 most probably preferentially works with Cygb and Ngb in tissues with low activity of CYB5R3. Reductases with wide specificity, thio-reductase 1 (TXNRD1) and NADPH:cytochrome-P450 reductase (CPR), function as reserve systems. In addition to their role in antioxidant protection and detoxification, they effectively reduce globins (especially Cygb and Ngb), showing the relationship between cell’s redox status and globin functions. All these systems not only support oxygen transport function of globins, but also regulate nitric oxide metabolism, providing vascular tone and protection against hypoxia and oxidative stress. Their dysfunction leads to pathologies, the most severe of which is hereditary methemoglobinemia.