Introduction to Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease.

Hydrolases constitute an enormous proportion of our enzymes, being responsible for the initiation of most digestive processes and numerous physiological processes. They are defi ned as enzymes that use a molecule of water to degrade substrates including all four kinds of biological molecules; namely, nucleic acids (nucleases), proteins (proteases), lipids or fats (lipases), and carbohydrates or sugars (glycosidases). They include large families of acyl ester hydrolases, phosphate, pyrophosphate ester and diester hydrolases, and amide ester hydrolases. Phospholipases constitute a class of hydrolases that catalyze the hydrolysis of acyl esters (deacylase activity) and phosphate esters (phosphodiesterase or phosphomonoesterase, also known as phosphohydrolase or phosphatase activity or sometimes pyrophosphatase activity) on phospholipids (diacylglycerophosphate esters and related compounds) ( 1 ). Phospholipases are defi ned by the position they hydrolize on the phospholipid backbone as shown in Fig. 1 . Of course, many enzymes are named based on the initial assay used to discover or defi ne their activity and then are later discovered to exhibit additional activities, and often their predominant physiological activity is quite different than their name implies. Also, there are certainly many enzymes not named as phospholipases that exhibit phospholipase activity, sometimes as a side or minor activity when presented with the appropriate phospholipid substrate. Sphingolipids constitute a separate category of lipids from phospholipids ( 2, 3 ), yet they reside similarly in membranes and functionally often play similar roles to phospholipids with some overlapping biosynthetic pathways. Some of the enzymes that hydrolyze sphingolipids carry out similar reactions to the phospholipases, such as sphingomyelinase, which exhibits a phospholipase C activity toward sphingomyelin, but additionally there are deamidases that hydrolyze the acyl amide on the ceramide backbone of sphingolipids and glycosidases that hydrolyze carbohydrates of glycosphingolipids. Such enzymes are not included in this Thematic Review Series but are reviewed elsewhere ( 4 ).