Nitric oxide in vascular biology: elegance in complexity

Abstract

As a graduate student at the University of Pennsylvania many years ago, I read journals and wrote my thesis in the Biochemistry Department’s library, the walls of which were adorned with photomicrographs of crystals of hemoglobin. These elegant images were taken by David Drabkin, who is best known for the development of a colorimetric reagent used to quantify hemoglobin in whole blood. He was, however, also an excellent physical biochemist, who first crystallized human hemoglobin and explored its spectrophotometric properties and those of some of its derivatives (1). Among the many derivatives and adducts of hemoglobin that gained increasing importance over the past 60 years is that of nitrosyl-hemoglobin, which forms when deoxy-hemoglobin is exposed to nitric oxide (NO) (2). This interaction with heme iron is one of many biochemical reactions in which NO is engaged and accounts for a plethora of functional effects in mammals (Figure 1). One example includes the activation of guanylyl cyclase that occurs with the binding of NO to the enzyme’s prosthetic heme group. Little did I realize at the time that an important part of my own research career would focus on this deceptively simple heterodiatomic molecule and its pathobiological actions. NO and heme in prebiotic and biotic evolution NO probably first appeared in the prebiotic phase of geochemical evolution approximately 4.5 to 2.5 […].