Pancreatic colipase: chemistry and physiology.

The first indication for the existence of a cofactor for pancreatic lipase was reported in 1910 by Rosenheim (1 ) . This paper is of some historical interest and contains the following statement: “It seems therefore that pancreatic lipase is a complex enzyme which can be separated into two inactive fractions by means of filtration, a fact which has so far not been observed in any other enzyme”. The term co-enzyme of pancreatic lipase was proposed for the heat-stable substance that was contained in the clear filtrate of a glycerol extract of pig pancreas. Whether this “co-enzyme” is identical to the cofactor now discussed is unclear. It was not until 1963 that the existence of a lipase cofactor was again documented. That year Baskys, Klein, and Lever (2) reported the separation by ion exchange chromatography of a heat-stable cofactor for lipase. These authors did not follow up their findings, but it is important for an understanding of the further developments that the lipase assay used by Baskys et al. (2) contained 8 mM deoxycholate. Sarda et al. (3) were not able to confirm the observations of Baskys et al. (2) and the reason for this, most probably, has to be sought in differences in the lipase assay system. The substrate used by Sarda et al. (3) may not have contained bile salts in a concentration high enough to cause inhibition of the lipase, or the cofactor may not have been completely separated from the enzyme. In 1969 Morgan, Barrowman, and Borgstrom (4) confirmed the results of Baskys et al. (2). They separated lipase from a heat-stable cofactor by gel filtration and could assign an approximate molecular size to the cofactor corresponding to = 12,000 daltons. Of importance was the finding that the cofactor-free lipase was inactive when tested against substrate containing supramicellar concentrations of bile salts, but it retained its activity against a detergent-free tributyrin emulsion. It was subsequently realized that pure pancreatic lipase is inhibited by bile salts in concentrations over their critical micellar concentration (CMC) and that the function of the cofactor is to restore lipase activity in the presence of bile salt (5,6). In the meantime, the cofactor had been partially purified and named colipase by Maylie et al. (7). The following is an account of the present state of knowledge in this field which includes the chemistry, physical chemistry, and physiological chemistry of pancreatic colipase and its interactions.