Pepsinogens in Health and Disease

Pepsinogens, precursors of pepsins (potent and abundant digestive enzymes that are the primary products of the gastric chief cells), are members of the family of aspartic proteases. Because of the heterogeneity of pepsinogens, several classifications have appeared in the literature. I describe the recommended classification and nomenclature of the aspartic proteases and discuss their genetics, biochemistry (structure, activation of zymogens, mechanism of proteolytic activity and inhibitors), and physiology. The focus will be on the zymogens of pepsin, the so-called pepsinogens. The measurement of these enzymes in serum is a reliable noninvasive biochemical method for evaluating peptic secretion and obtaining information on the gastric mucosal status. A detailed review of the methods for the measurement of pepsinogens in serum, urine, and gastric mucosa is also provided. Data on pepsinogen levels in healthy subjects are discussed with respect to sex, age, smoking habit, and the presence of a circadian rhythm. The value of pepsinogen measurements in peptic ulcer to determine ulcer outcome and recurrence, in gastric cancer, and in Helicobacter pylori infection is reviewed. Finally, the effects of drugs on peptic secretion are discussed. In light of these data, the measurement of aspartic proteases, and in particular that of pepsinogen A and C, may be regarded as an effective biochemical approach to the evaluation and monitoring of patients with upper gastrointestinal diseases.