Heme synthesis in vitamin B6 and pantothenic acid deficiencies.

Shemin and coworkers (14) showed that the a-carbon and nitrogen atoms of glycine were precursors of specific atoms of the heme molecule. This was substantiated by Muir and Neuberger (5, 6). Other carbon atoms were shown to come from acetate (5-7) or succinate (8). The nature of the intermediate precursors synthesized from these metabolites remained unknown until the structure for urinary porphobilinogen’ was elucidated (9-13). Falk et al. (14) found PBN to be incorporated into porphyrins and heme in avian red cells. Subsequently, Shemin and Russell (15) and Neuberger and Scott (16) independently synthesized b-aminolevulinic acid’ and found that it was a precursor of porphyrins and heme. An enzyme was soon shown to be present in nature, which readily converts ALA to PBN (17-21) and has been named &aminolevulinic acid dehydrase by Gibson et al. (22). Shemin and Russell (15) proposed that ALA is biosynthesized from glycine and an asymmetric succinyl derivative, perhaps succinyl coenzyme A, by the condensation of these substances to form a-amino, ,3-ketoadipic acid, which is subsequently decarboxylated. Vitamin Ba and pantothenic acid are among a variety of nutritional substances which, when fed in inadequate amounts, may result in anemia. Anemia from vitamin Be deficiency has been reported in such species as dog (23), pig (24), rat (25), duck (26), and chick (27). Cartwright and Wintrobe (28) suggested that in swine the fundamental disturbance is a failure to synthesize protoporphyrin, since low erythrocyte protoporphyrin levels were found in this deficiency. An anemia from pantothenic acid deficiency has been described by several groups of investigators (29-31). However, in rats it appears that special conditions such as the simultaneous deficiency of additional food essentials (32) may be necessary for anemia to appear. The purpose of these studies was to see whether the rates of incorpora-