Inositol-specific phospholipase D activity in health and disease.

1. We report the first demonstration of the pathophysiological importance and clinical applications of the relatively recently discovered circulating enzyme, phosphoinositol-specific phospholipase D. This enzyme is known to cleave the large variety of important cell-surface molecules linked to the cell membrane by glycan-phosphatidylinositol linkages (glycan-phosphatidylinositol anchors). 2. When measured in the sera of healthy individuals, phosphoinositol-specific phospholipase D activity was found to show a strong negative correlation with age, the degree of depreciation being greater than that measured for most other analytes. 3. Serum phosphoinositol-specific phospholipase D activity was considerably depressed in patients presenting with conditions leading to reduced liver synthetic reserve, such as hepatocellular carcinoma or liver cirrhosis caused by chronic viral hepatitis, and correlated with reduced albumin levels in these conditions, indicating that the liver is the site of phosphoinositol-specific phospholipase D synthesis and that phosphoinositol-specific phospholipase D may be used as an additional marker of liver synthetic reserve. 4. When measured in patients with acute liver disease, such as acute viral hepatitis, or in patients with bronchopneumonia, phosphoinositol-specific phospholipase D activity was found to be significantly raised, demonstrating features characteristic of an acute-phase reactant. 5. These findings indicate that, besides its pathophysiological importance, phosphoinositol-specific phospholipase D and the measurement of its activity in serum may have a useful place in the investigation of a range of clinical conditions, including tissue injury and inflammation.