STUDIES OF THE PRINCIPLE IN LIVER EFFECTIVE IN PERNICIOUS ANEMIA. IV. THE THERAPEUTIC ACTIVITY OF ITS MULTIPLE FACTORS 12

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Abstract
Continued purification of commercial liver extract yielded at least 4 chemically distinct substances which appear to be concerned in the therapeutic activity of liver extract in pernicious anemia. One of these substances, of unidentified chemical nature, is termed the primary factor, while the other 3 are termed accessory factors. The 3 accessory factors have been identified as Z-tyrosine, a complex purine, and a peptide, respectively. The intramuscular administration of the primary factor without all 3 of the accessory factors resulted in submaximal reticulocyte responses, and in either no erythrocyte response or in slight, ill-sustained erythrocyte rises. On the other hand, the administration of all 4 factors resulted in reticulocyte and erythrocyte responses approximating that of the same quantity of commercial liver extract. The accessory factors, in the absence of the primary factor were therapeutically completely inert. The satisfactory therapeutic activity of the 4 factors together did not depend upon an additive effect, but rather represented an augmentation of the activity of the primary factor by the accessory factors.

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