Diverse biological activities of the vascular non-inflammatory molecules - the Vanin pantetheinases

Abstract

The Vanin genes are a family that encode pantetheinases involved in recycling Coenzyme A, catalysing the breakdown of intermediate pantetheine to vitamin B5 for reuse in CoA biosynthesis. The role of pantetheinase in this most fundamental of cellular processes, was substantially characterised by the 1970s. The next 20 years saw little further interest in pantetheinase until various genetic studies implicated the Vanin locus in a range of normal and disease phenotypes, and a consequent interest in the other product of pantetheinase activity, cysteamine. This report seeks to bring together the early biochemical studies with recent biological data implicating cysteamine as a regulator of the oxidative state of a cell. Numerous studies now report a role for Vanin in inflammation, oxidative stress, cell migration and numerous diseases including cardiovascular disease.

Figure 1

Human Vanin family structural predictions. Predicted N glycosylation sites shown as underscored residues in green: N-Signal peptides in bold; predicted active site residues (based on biotinidase) boxed in red including * ; predicted α-helices in yellow (light shading); predicted β-sheets shaded in grey (dark); predicted GPI-anchor site residues in white with blue box; * identical residues; : conservative substitution; . non-conservative substitution; Missense residue in VNN3 shown in strikeout and red has been changed to allow readthrough to the predicted stop codon.

Figure 2

Substrates and metabolites of Vanin Activity.

Figure 3

Overview of the main pathways influenced by Vanin Activity.