The primary structure of glucose‐6‐phosphate dehydrogenase from rat liver has been determined, showing the mature polypeptide to consist of 513 amino acid residues, with an acyl‐blocked N‐terminus. This structure is homologous to those of both other eutherian and marsupial mammals (human and opossum), thus characterizing a mammalian type enzyme to which the human form, notwithstanding its large number of genetic variants, conforms. The mammalian type differs from the fruit fly enzyme by about 50%. Known mutant forms exhibit further differences, widely distributed along the polypeptide chain. Structural patterns show glucose‐6‐phosphate dehydrogenases to consist of a few variable regions intermixed with relatively constant segments.

The NH2-terminal region of rat liver glucose-6-phosphate dehydrogenase (EC 1.1.1.49) is shown to differ radically from a reported amino acid sequence for the fruit fly enzyme and from one for the human enzyme. The results indicate considerable differences in the translational start point. However, a close relationship with another reported sequence for the human enzyme is established, now showing agreement between an indirectly deduced and a directly analyzed NH2-terminal structure of this enzyme type. The results provide evidence of one structural motif common to mammalian species but also suggest that genetic inconstancy 5' to, or at the start of, the region coding for the enzyme protein could be a source of intra-and interspecies diversity. This is of interest in relation to the large number of genetic variants of human glucose-6-phosphate dehydrogenase.