A comparative study on the NH2-terminal amino acid sequences and some other properties of six isozymic forms of human pepsinogens and pepsins.
Six pepsinogen isozymogens, including five forms of pepsinogen A (PGA) and an apparently single form of pepsinogen C (PGC), were isolated simultaneously from the purified total pepsinogen fraction of human gastric mucosa by fast protein liquid chromatography on a Mono Q column, and their NH2-terminal amino acid sequences and some other properties were compared. Upon activation at pH 2.0, all the isozymogens were converted to the corresponding pepsins in a stepwise manner through intermediate forms. The activation rates and the cleavage sites in the activation peptide segment to generate intermediate forms were significantly different among the isozymogens. The NH2-terminal 85-residue amino acid sequences of these isozymogens were determined, including the sequences of the activation peptide segments and the NH2-terminal regions of the corresponding pepsins. Differences in amino acid sequence were found at positions 43 and 77 among the pepsinogen A isozymogens; the residue at position 43 was Lys in PGA-5, PGA-4, and PGA-3a, and Glu in PGA-3 and PGA-2, and the residue at position 77 was Leu in PGA-5 and PGA-4 and Val in PGA-3 and PGA-2. Phosphate was not found in any of the isozymogens. The corresponding pepsins also showed significant variations in properties such as specific activities toward synthetic and protein substrates, pH dependence of activity, susceptibility to various inhibitors, and thermal and alkaline stabilities.
Athauda
S B
SB
Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo.
Tanji
M
M
Kageyama
T
T
Takahashi
K
K
D000595:Amino Acid Sequence; D002241:Carbohydrates / Q000032:analysis; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000302:isolation & purification / Q000378:metabolism; D010435:Pepsinogens / Q000302:isolation & purification / Q000378:metabolism; D010710:Phosphates / Q000032:analysis
D002241:Carbohydrates; D007527:Isoenzymes; D010435:Pepsinogens; D010710:Phosphates; D010434:Pepsin A