The Human and Mammalian N-Acetylmuramyl-L-alanine Amidase: Distribution, Action on Different Bacterial Peptidoglycans, and Comparison with the Human Lysozyme Activities

Abstract

N-acetylmuramyl-L-alanine amidase (EC 3.5.1.28) specifically hydrolyzes the bacterial cell wall peptidoglycans (or mureins) and the muropeptides. The enzyme splits these molecules into two parts: the peptide subunits and the glycan strands or moieties. The bacterial peptidoglycans and their derived muropeptides display a number of biological properties. Removal of the glycosidic part of these molecules abolishes their beneficial as well as their detrimental properties. We report the high level of enzymatic activity found in all mammalian (including human) sera tested. The enzyme also occurred in human saliva, milk, cerebrospinal fluid, and synovial liquid. Mucosal tissue from different parts of the mammalian digestive tract exhibited enzymatic activity, but the enzyme was not detectable in the lumen content. The range of substrate specificity of the human enzyme was evaluated by measuring its action on the peptidoglycans extracted from several bacterial strains and representing different chemotypes and structures. Time course of the muramylalanine amidase and of the lysozyme (both of human origin) activities on some of these peptidoglycans are also reported, with the enzymes acting separately or together. From these data, we would speculate that a probable physiological role of the muramylalanine amidase is the maintenance of adequate ratios between the biologically active muropeptides and their inactive derivatives in the organism, the amidase activity antagonizing the production of biologically active molecules by lysozyme.