5 HUMAN GASTRIC ASPARTIC PROTEINASES - N-TERMINAL AMINO-ACID-SEQUENCES AND AMINO-ACID-COMPOSITION

Human pepsin A consists of 4 or more isoenzymes (designated 1, 3a, 3b and 3c) one of which, pepsin 1, contains up to 50% carbohydrate moieti es. The amino-acid composition and N-terminal sequence of pepsin 1 and the other isoforms have been determined and compared with data obtain ed for pepsin 3b and gastricsin (pepsin C or pepsin 5). Pepsins were i solated from penta-gastrin stimulated gastric juice using repetitive c hromatography on DEAE-cellulose, or high performance ion-exchange chro matography. Sequencing,vas performed using automated solid-phase Edman degradation with a microsequence facility. The amino-acid composition s were similar for pepsins 1, 3a, b and c and the N-terminal sequences of pepsins 1, 3a and c, reported for the first time, were shown to be identical with that for pepsin 3b (the main component of pepsin A) al though residue 28 was unassigned in pepsin 1. Residue 30 in all four i soenzymes is valine and we cannot confirm reports of major pepsins wit h leucine in this position. For gastricsin the sequence differed from the pepsin isoenzymes and in position 24 we find pro rather than ala a s was first described, These observations suggest that pepsin 1 is ide ntical to 3b or a mixture of 3a, 3b and 3c but not gastricsin. This da ta supports the hypotheses that the four pepsin isoenzymes are product s of the same gene(s) but have undergone varying levels of post transl ational modification.