The Journal of Biological Chemistry’s thematic minireview series “Metals in Biology” is back for a fifth edition. While metals play crucial roles in many biological functions, our understanding of those roles is lacking. This series features metals in biochemistry and human health and is coordinated by F. Peter Guengerich of Vanderbilt University, a JBC associate editor. The first two editions of “Metals in Biology” discussed iron, copper, selenium, zinc, nickel, vanadium and arsenic, the third focused on iron homeostasis and eukaryotic cells, and the fourth concentrated on metal transport and homeostasis. The latest collection of minireviews covers the molybdenum prosthetic group, or pterin Moco; the biosynthesis of M-cluster molybdenum prosthetic group of nitrogenase; the biosynthesis of the nickel-based metallocenter of the enzyme urease; several of the processing, transport and medical aspects of cobalamins; and the growing roles of heme sensor proteins.
The first article begins with a review on the biological assembly of the molybdenum prosthetic group, or Moco. Molybdenum is an essential micronutrient for plants and animals and functions as a cofactor for enzymatic activity; however, it is catalytically inactive unless bound by a special scaffold, one of which is the molybdopterin or metal-containing pterin (MPT). The review by Ralf R. Mendel covers uptake of molybdenum by eukaryotes, the molybdenum prosthetic group Moco, the details and requirements for the biosynthesis of Moco, Moco storage and transfer, and Moco deficiency disorders and therapy in humans.
Moco forms part of the active centers of all molybdenum-containing enyzmes except bacterial nitrogenase, an enzyme vital in agriculture because it reduces atmospheric nitrogen to ammonia. Instead of Moco, nitrogenase contains an iron-sulfur cluster-based molybdenum group. In the second minireview, Yilin Hu and Markus W. Ribbe discuss the recent progress in understanding the biosynthesis and assembly of the iron-molybdenum cluster FeMoco.
According to the authors of the third minireview, “Biosynthesis of the Urease Metallocenter,” “metallocenters serve essential biological functions such as transferring electrons, stabilizing biomolecules, binding substrates, and catalyzing desirable reactions.” Furthermore, authors Mark A. Farrugia, Lee Macomber and Robert P. Hausinger explain that metallocenters are required for metal homeostasis and mediating conformational changes that result in enzyme activity. The authors focus on biosynthesis of the metallocenter of urease, a nickel-containing enzyme in bacteria and plants, to understand the mechanisms of the metallocenter assembly system. Their review introduces ureases, the urease activation pathway and variations in urease activation systems.
In the fourth minireview, “Navigating the B12 road: assimilation, delivery and disorders of cobalamin,” Carmen Gherasim, Michael Lofgren and Ruma Banerjee discuss trafficking of the biochemistry of cobalamin in mammals and the human diseases that result from impairments in the pathway. The article covers vitamin B12 chemistry; absorption, transport, and storage of cobalamin; cobalamin processing; and incorporation of cobalamin into biological pathways.
In the final review, Hazel M. Girvan and Andrew W. Munro explore the role of the prosthetic group heme, which is best known for its role in oxygen transport as a biological sensor. They review recent discoveries on the role of heme in regulating circadian rhythms, ion channel activity and microRNA biogenesis, gas sensing and regulating microbial respiration and denitrification.