The History of the Molybdenum Cofactor—A Personal View

Abstract

The transition element molybdenum (Mo) is an essential micronutrient for plants, animals, and microorganisms, where it forms part of the active center of Mo enzymes. To gain biological activity in the cell, Mo has to be complexed by a pterin scaffold to form the molybdenum cofactor (Moco). Mo enzymes and Moco are found in all kingdoms of life, where they perform vital transformations in the metabolism of nitrogen, sulfur, and carbon compounds. In this review, I recall the history of Moco in a personal view, starting with the genetics of Moco in the 1960s and 1970s, followed by Moco biochemistry and the description of its chemical structure in the 1980s. When I review the elucidation of Moco biosynthesis in the 1990s and the early 2000s, I do it mainly for eukaryotes, as I worked with plants, human cells, and filamentous fungi. Finally, I briefly touch upon human Moco deficiency and whether there is life without Moco.

The Mechanisms of Molybdate Distribution and Homeostasis with Special Focus on the Model Plant Arabidopsis thaliana

“…Although more than 50 molybdo-enzymes belonging to three families are known in nature, the majority are of prokaryotic origin and only a few were found in eukaryotes [ 31 ]. The families are defined by the kind of Moco.…”

“…In plants, Moco is used by five molybdo-enzymes that catalyze key reaction steps in the metabolism of carbon, nitrogen, and sulfur. This, a broad variety of redox reaction, is catalyzed by a two-electron transfer, varying the oxidative state of the molybdenum atom between IV and VI [ 31 ]. The aldehyde oxidase (AO) and the xanthine dehydrogenase (XDH) belong to the XO family, while the nitrate reductase (NR), the sulfite oxidase (SO), and the mitochondrial amidoxime-reducing component (mARC) belong to the SO family.…”

Function of Molybdenum Insertases

“…In the fourth step of the pathway, molybdate is inserted by the E-domain, yielding Moco-AMP (termed adenylated Moco [ 14 ]) which is subsequently hydrolyzed to yield Moco. For a recent summary describing the Moco biosynthesis pathway see Ralf Mendel´s review in this Special Issue [ 24 ].…”

Studying Peptide-Metal Ion Complex Structures by Solution-State NMR

“…Molybdenum is the only 5th row element among the essential metals and is only biologically active upon complexation to form a molybdenum cofactor [133]. Deficiency in the molybdenum cofactor results in a fatal metabolic disorder [134].…”