Prolonged Hyperlipasemia Attributable to a Novel Type of Macrolipase

We present the case of an 80-year-old woman who was admitted to hospital with an intermittent volvulus of the right colon. A total colectomy was performed. Initially, serum amylase and lipase increased concordantly, but after a few weeks amylase normalized (85 U/L), whereas lipase increased to 3764 U/L. This discrepancy and persistence of hyperlipasemia suggested a macromolecular form of lipase. The nature of the macromolecular complex was studied using high-pressure liquid gel-permeation chromatography, affinity chromatography, (immuno)electrophoresis, and immunodiffusion. Gel-permeation chromatography revealed a macrolipase, with a molecular mass >900 kDa, that contributed up to 56% of total serum lipase activity. Butanol extraction of the specimen did not alter the elution profile. The thermostabilities of pancreatic lipase and the macroform were similar, whereas activation energy (E:(a)) was lower in the macromolecular lipase (28 +/- 4 kJ. mol(-1). K(-1) vs 48 +/- 7 kJ. mol(-1). K(-1) (P: = 0.02). Agarose electrophoresis showed a broad band of lipase activity at the application site. Protein A-Sepharose affinity gel chromatography excluded IgG-linked lipase. Agarose electrophoresis and immunofixation excluded linkage to other immunoglobulins. Radial immunodiffusion did not show lipase activity in the immunoglobulin precipitation bands. Radial immunodiffusion with alpha(2)-macroglobulin (alpha(2)-MG) antibodies showed a diffuse spot of lipase activity within the precipitation band, suggesting a macromolecular association between lipase and alpha(2)-MG. Affinity gel chromatography against alpha(2)-MG showed lipase activity in the alpha(2)-MG-bound fractions. This is the first report of a macrolipase in which an association between alpha(2)-MG and lipase is described.