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Ludwig Oxford’s Peter Ratcliffe and Tom Keeley have undertaken a comparative analysis of a number of enzymes involved in the adaption of cells to oxygen level changes.

Animal adaption to changes in cellular oxygen levels is primarily coordinated by 2-oxoglutarate dependent prolyl-hydroxylase domain (PHD) dioxygenase family members which regulates the stability of hypoxia-inducible factor (HIF) substrates to promote expression of genes that adapt cells to hypoxia. The Ratcliffe group at Ludwig Oxford also recently identified 2-aminoethanethiol dioxygenase (ADO) as a novel oxygen-sensing enzyme in animals, and have now undertaken a comparative analysis of the in cellulo characteristics of ADO and PHD enzymes to better understand their co-evolution in animals.

Ya-Min Tian and co-workers within the Ratcliffe group show that ADO and PHD/HIF systems have a similar sensitivity to oxygen and might interact should they share common targets. The findings showed that although ADO and PHD enzymes share similar kinetic properties relating to oxygen, the reactions catalysed by each are distinct. These finding and others, discussed in detail in the paper published in the Journal of Biological Chemistry, provide evidence for ADO acting as a physiological oxygen sensor operating in cells alongside, and interacting with, HIF. The ADO system responds at similar levels of oxygen concentration to those inducing HIF but its direct action enables the transduction of responses to altered oxygen levels on a shorter time-scale.

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