Amino Acids: Riddles from A to Y.

Abstract

The recent Food and Drug Administration approval of the use of L-glutamine for the reduction of pain episodes in patients with sickle cell disease (SCD)2 highlights the importance of familiar amino acids in new therapeutics. For example, lysine analogs are used as antifibrinolytics to stop bleeds, whereas an arginine analog is used as an antithrombotic agent. What is the mechanism of action of L-glutamine in SCD? L-glutamine has a favorable impact on the ratio of reduced to total NAD and redox potential in sickle red blood cells (RBCs) exposed to oxidative stress (1). RBCs from individuals with SCD who were treated with L-glutamine showed reduced sickling on the peripheral blood smear and were less sickled and less adherent to vascular cells than RBCs from untreated individuals (2). Oral L-glutamine also reduced endothelial adhesion of sickle RBCs to human umbilical vein endothelial cells (3). Improved redox biology might make sickle RBCs less adhesive. Both tranexamic acid and e-aminocaproic acid, which are analogs of lysine, competitively block the binding of fibrinogen and fibrin to their lysine binding sites on plasminogen, thus reducing the rate of fibrinolysis. Aprotinin, a serine protease inhibitor, has been removed from the market due …