Figure 5.

Schematic illustration of the metabolic fate of arginine in platelets in sickle cell disease. Under normal situations, arginine will be taken up by the platelets via cationic amino acid transporter-2 (CAT-2) for the synthesis of NO and polyamines, which protect cells from activation and aggregation. In sickle cell disease, increased arginase activity and consequent limitation in arginine bioavailability is expected to impair NO synthesis, whereas reduced polyamine levels will enhance platelet aggregation. The increased production of ornithine via arginase II (ARG-2), instead of going toward polyamine synthesis, would be diverted toward proline synthesis, consistent with increased levels of mRNA encoding pyrroline-5-carboxylate reductase (P5CR). Increased expression of enzymes is indicated by the red upward-pointing arrows and red highlighting of enzymes. ODC indicates ornithine decarboxylase; SRM, spermidine synthase; SS, spermine synthase; and antizyme, ornithine decarboxylase antizyme.