   |
|
|
Mahin Maines Background: Heme metabolism is an important metabolic process because many important proteins, such as hemoglobin and cytochromes, contain heme as a prosthetic group. When these hemoproteins are broken down, the heme is not salvaged, but is degraded. The enzyme biliverdin reductase (BVR) catalyzes the last step in heme degradation by converting biliverdin to bilirubin. While biliverdin is a potent liver tumor promotor, it has also been shown to inhibit herpes virus and HIV-1 replication. Low levels of bilirubin, an antioxidant, have been associated with coronary artery disease. The balance of biliverdin to bilirubin conversion maintained by BVR is therefore a very important process in cellular defense mechanisms. Advance: These researchers have determined that BVR must be phosphorylated to carry out the reduction of biliverdin to bilirubin. They have shown that BVR is actually a kinase, and can autophosphorylate itself. These findings suggest that the reversible phosphorylation of BVR is an important mechanism by which activities of heme degradation products are regulated. Implication: Enzyme phosphorylation is an important component of the regulation of intermediary metabolism. Many enzymes must be phosphorylated to catalyze reactions; however, only a small fraction of them are reversibly autophosphorylated. The significance of BVR phosphorylation may be related to the important role of the heme oxygenase system in cellular defense mechanisms and the complex interactions between the enzymes and products of the heme degradation pathway. Many important cellular responses are regulated by phosphorylation cascades triggered by signal transduction pathways. Publication: Salim M, Brown-Kipput BA, Maines MD. Human biliverdin reductase is autophosphorylated, and phosphorylation is required for bilirubin formation. J Biol Chem. 2001 Apr 6;276(14):10929-34. |
|
   |
|
|