Parallel Secretion of Pancreatic Phospholipase A2, Phospholipase A1, Lipase, and Colipase in Children with Exocrine Pancreatic Dysfunction

Abstract

The cosecretion of pancreatic lipase and colipase are important in normal fat digestion. As adsorption of phosphatidylcholine to the lipid substrate interferes with lipase activity, hydrolysis to lysophosphatidylcholine with subsequent desorption is also essential for fat digestion. There are some data regarding the secretion of pancreatic phospholipases in normal adults but none in children or patients with pancreatic disease. In the present study, we aimed a) to develop an accurate fast assay method to measure phospholipase A 2 and b) to determine the secretion rate of pancreatic phospholipase A 2 and whether it is cosecreted with lipase and colipase in children with exocrine pancreatic dysfunction. Nine male patients aged 0.5 to 16 y (seven with cystic fibrosis, two with malabsorption) underwent pancreatic stimulation tests. Their colipase and lipase secretion rates were measured by titrimetric methods and phospholipase A 2 and A 1 by phosphorus magnetic resonance spectroscopy ( 31 P NMR). It was found that the phospholipases, colipase, and lipase were absent in the two patients with pancreatic insufficiency. In patients with normal absorption, there were marked inter-and intrasubject variations of lipase, colipase, and phospholipase secretion rates that were consistent with the degree of exocrine pancreatic dysfunction. However, in the three 20-min stimulation periods of the pancreatic function test, pancreatic phospholipase is cosecreted with lipase and colipase, and average colipase and phospholipase A 2 secretion rates follow a similar or parallel pattern. These findings are consistent with the important role of pancreatic phospholipases in intestinal phospholipid hydrolysis leading to the desorption of phospholipids from the lipid substrate and enhancing lipid hydrolysis and phospholipid absorption. Abbreviations CEH, carboxyl ester hydrolase CF, cystic fibrosis GPC, glycerophosphocholine lysoPC, lysophosphatidylcholine MCC, mucocutaneous candidiasis and polyendocrinopathy NMR, nuclear magnetic resonance PC, phosphatidylcholine PLA 1 , phospholipase A 1 PLA 2 , phospholipase A 2 PI, pancreatic insufficient PS, pancreatic sufficient Exocrine pancreatic function has been well characterized in children with pancreatic disease with the use of quantitative pancreatic function tests (1-3). To determine the relationship between residual pancreatic function and fat absorption, sensitive titrimetric assays were developed for lipase and the lipase cofactor colipase (4) and their secretion rates compared with fecal fat excretions in children with CF, Shwachman syndrome, or controls (3,5). These studies demonstrated that patients with normal fat absorption had a wide range of enzyme/coenzyme secretion from less than 5% up to within the normal control range; and the threshold for lipolytic failure was near 1% of average control colipase values, i.e. patients with values below this level had fat malabsorption and above this level normal absorption. These observations led to the currently accepted definition that patie...

Human pancreatic exocrine response to nutrients in health and disease

“…187 Pancreatic enzymes involved in lipid digestion such as lipase, colipase, and phospholipase were decreased in parallel in children with cystic fibrosis. 188 Impaired pancreatic lipase secretion might in part be compensated by a moderate increase in gastric lipase activity and intragastric lipolysis. 189 Duodenal pancreatic enzyme output in response to a meal or meal components has rarely been studied in cystic fibrosis, probably because of the invasive character of these investigations and the young age of most patients.…”

Diagnosis and Treatment of Intestinal Malabsorption in Cystic Fibrosis

“…68 Consideration should be given to changing to another brand of enzyme that, in the same dose, may result in a quite dramatic improvement in symptoms and absorption. Presumably the many differences in pharmacological characteristics may be relevant to their differing performance in practice, including their quantitative and qualitative enzyme content, 95 dissolution characteristics, 60 and size of the particles. 61,62 The individual differences in dose requirements, even in patients with little or no residual pancreatic function, are presumably due, in part, to these brand differences.…”

Plasma Phosphatidylcholine Alterations in Cystic Fibrosis Patients: Impaired Metabolism and Correlation with Lung Function and Inflammation

“…In human CF patients, fecal losses of choline metabolites derived from biliary phosphatidylcholine (PC), are increased despite pancreatic enzyme replacement. Fecal losses of undigested PC are 9-fold increased, suggesting that impaired pancreatic phospholipase A 2 (pPLaseA 2 ) function is causative here, and choline deficiency may be central to metabolic alterations in CF [13,14,15]. …”