An enzyme's active site determines its reactivity
Phospholipases are enzymes that cleave the tail group off of phospholipids, which make up cell membranes. These tails, or free fatty acids, can go on to act as signaling molecules. Lysosomal phospholipase A2, or LPA2, is a phospholipase from the macrophages that protect the lung. The enzyme is unusual in interacting with a wide range of substrates, and making two types of modification to phospholipids, acting as either an acyltransferase (which attaches the freed fatty acid tail to a new molecule) or phospholipase (which lets the free fatty acid go). Unlike many phospholipases, which are active at neutral pH, LPA2 is most active in the highly acidic environment typical of the lysosome.
To figure out why LPA2 has such strange enzymatic properties, researchers at the University of Michigan honed in on Asp13, a recently identified catalytic residue on the enzyme. A recent paper in the Journal of Lipid Research describes how substituting a variety of amino acids for Asp13 made LPA2 more active at neutral pH and less able to interact with the unsaturated acyl chains that it had previously favored. The study gives molecular insight into LPA2 activity.
Why do kidney disease and heart failure correlate?
People with chronic kidney disease are at unusually high risk of also developing cardiovascular disease; in fact, a patient with non-dialysis kidney disease is more likely to die of heart failure than to develop end-stage kidney failure. However traditional atherosclerosis risk factors contribute less strongly to cardiovascular disease in chronic kidney disease patients than in subjects with intact kidney function. Researchers are still trying to figure out how chronic kidney disease is linked to cardiovascular disease and how best to prevent it. In a recent study in the Journal of Lipid Research, Kathrin Untersteller and colleagues at Saarland University Medical Center in Germany and the Medical University of Graz in Austria undertook a detailed longitudinal study of patients with chronic kidney disease who were not on dialysis.
Altered kidney function is known to change the protein content of high-density lipoproteins, or HDL, which are inversely correlated with heart disease in the general population. Untersteller and colleagues hypothesized that that the level of HDL (known as "good cholesterol") or its protein makeup in a patient's serum at enrollment could predict the risk of cardiovascular disease in the next five years. Contrary to their expectation, after conducting the study the researchers concluded that, although some characteristics of HDL correlated weakly with future heart disease risk, no characteristic could be used independently to predict risk after controlling for other risk factors. The study underscores the complexity of untangling causality in clinical studies.
About the Journal of Lipid Research
The Journal of Lipid Research (JLR) is the most-cited journal devoted to lipids in the world. For over 50 years, it has focused on the science of lipids in health and disease. The JLR aims to be on the forefront of the emerging areas of genomics, proteomics, and lipidomics as they relate to lipid metabolism and function. For more information about JLR, visit http://www.