Processing reactions in the later stages of hormone activation

Three tiers of processing have been investigated in the reactions that transform prohormones into their mature end products. Evidence is presented that the proteolytic reactions that convert lipotropin into shortened forms of beta-endorphin take place in individually distinct stages. After these cleavages have occurred, the removal of basic residues by carboxypeptidase H and amidation of the products are effected by independent reactions which do not synergise. Experiments are also described which show that the amidating enzyme can accept certain imino acids as substrates and utilises a mechanism that involves hydroxylation; it is implicit that peptide amidation proceeds by a similar mechanism. These results point to a general concept that pro-hormone processing involves consecutive reactions which take place in a predetermined order.