Significance of the molecular heterogeneity of gut hormones.

Molecular heterogeneity is a fundamental feature of ribosomally synthesized proteins and polypeptides. The heterogeneity reflects gene duplications with subsequent differences in mutation of the genes, different post-transcriptional and post-translational processings and different amino acid modifications. Gut hormones are also heterogeneous, but the degree of heterogeneity reported so far for each hormone has varied. The most extensively studied (i.e. cholecystokinins, gastrins, opioid peptides and glucagons) have displayed a high degree off heterogeneity. Similar degrees will probably emerge for the remaining gut hormones when they have been studied in greater detail. In accordance with the nature of the molecular difference, a distinction between macro- and microheterogeneity is proposed. Macroheterogeneity is caused by variations in peptide chain length; microheterogeneity by derivatizations or substitutions in single amino acid residues. The molecular heterogeneity has profound implications for measurement and study of a gut hormone. Thus, measurement in biological fluids requires careful evaluation of the number and affinity of different molecular forms. Understanding of the function and pathophysiology of gut hormones requires full clarification of their molecular heterogeneity.