Vitamin C biosynthesis pathway and transportation in animals. Vitamin C is synthesized from d-glucose in most mammals. Through multiple enzymatic reactions, d-glucose is first oxidized to d-glucuronate, which is then reduced to l-gluconate and further into l-gulonolactone. In the final step, the enzyme GULO oxidizes l-gulonolactone to 2-keto-l-gulonolactone, which is then spontaneously converted into vitamin C (ascorbic acid). Humans, higher primates, guinea pigs, and fruit bats lack a functional form of GULO and therefore require dietary supplement. The reduced form of vitamin C, ascorbic acid, is transported into the cells through SVCT1/2 (sodium-dependent vitamin C transporters, encoded by Slc23a1 and Slc23a2), whereas its oxidized form, DHA, is transported into the cells through GLUT1/3/4 (glucose transporters). Slc23a1 is not expressed in hematopoietic cells; Slc23a2 is expressed at higher levels in HSPCs and multipotent progenitor cells compared with other, more committed hematopoietic progenitors and differentiated cell types.