Volume 28, Issue 1

Pteridines and their derivatives function as intermediates in the metabolism of several vitamins and cofactors, and their relevance to disease has inspired new efforts to study their roles as disease biomarkers. Recent analytical advances, such as the emergence of sensitive mass spectrometry techniques, new workflows for measuring pteridine derivatives in their native oxidation states and increased multiplexing capacities for the simultaneous determination of many pteridine derivatives, have enabled researchers to explore the roles of urinary pteridines as disease biomarkers at much lower levels with greater accuracy than with previous technologies or methods. As a result, urinary pteridines are being increasingly studied as putative cancer biomarkers with promising results being reported from exploratory studies. In addition, the role of urinary neopterin as a universal biomarker for immune system activation is being investigated in new diseases where it is anticipated to become a useful supplementary marker in clinical diagnostic settings. In summary, this review provides an overview of recent developments in the clinical study of urinary pteridines as disease biomarkers, covers the most promising aspects of advanced analytical techniques being developed for the determination of urinary pteridines and discusses the major challenges associated with implementing pteridine biomarkers in clinical laboratory settings.

Pterins are widely conserved biomolecules that play essential roles in diverse organisms. First described as enzymatic cofactors in eukaryotic systems, bacterial pterins were discovered in cyanobacteria soon after. Several pterin structures unique to bacteria have been described, with conjugation to glycosides and nucleotides commonly observed. Despite this significant structural diversity, relatively few biological functions have been elucidated. Molybdopterin, the best studied bacterial pterin, plays an essential role in the function of the Moco cofactor. Moco is an essential component of molybdoenzymes such as sulfite oxidase, nitrate reductase, and dimethyl sulfoxide reductase, all of which play important roles in bacterial metabolism and global nutrient cycles. Outside of the molybdoenzymes, pterin cofactors play important roles in bacterial cyanide utilization and aromatic amino acid metabolism. Less is known about the roles of pterins in nonenzymatic processes. Cyanobacterial pterins have been implicated in phenotypes related to UV protection and phototaxis. Research describing the pterin-mediated control of cyclic nucleotide metabolism, and their influence on virulence and attachment, points to a possible role for pterins in regulation of bacterial behavior. In this review, we describe the variety of pterin functions in bacteria, compare and contrast structural and mechanistic differences, and illuminate promising avenues of future research.