Catalase as a sulfide-sulfur oxido-reductase: An ancient (and modern?) regulator of reactive sulfur species (RSS).

Catalase is well-known as an antioxidant dismutating HO to O and HO. However, catalases evolved when metabolism was largely sulfur-based, long before O and reactive oxygen species (ROS) became abundant, suggesting catalase metabolizes reactive sulfide species (RSS). Here we examine catalase metabolism of HS, the sulfur analog of HO, hydrogen sulfide (HS) and other sulfur-bearing molecules using HS-specific amperometric electrodes and fluorophores to measure polysulfides (HS; SSP4) and ROS (dichlorofluorescein, DCF). Catalase eliminated HS, but did not anaerobically generate HS, the expected product of dismutation. Instead, catalase concentration- and oxygen-dependently metabolized HS and in so doing acted as a sulfide oxidase with a P of 20mmHg. HO had little effect on catalase-mediated HS metabolism but in the presence of the catalase inhibitor, sodium azide (Az), HO rapidly and efficiently expedited HS metabolism in both normoxia and hypoxia suggesting HO is an effective electron acceptor in this reaction. Unexpectedly, catalase concentration-dependently generated HS from dithiothreitol (DTT) in both normoxia and hypoxia, concomitantly oxidizing HS in the presence of O. HS production from DTT was inhibited by carbon monoxide and augmented by NADPH suggesting that catalase heme-iron is the catalytic site and that NADPH provides reducing equivalents. Catalase also generated HS from garlic oil, diallyltrisulfide, thioredoxin and sulfur dioxide, but not from sulfite, metabisulfite, carbonyl sulfide, cysteine, cystine, glutathione or oxidized glutathione. Oxidase activity was also present in catalase from Aspergillus niger. These results show that catalase can act as either a sulfide oxidase or sulfur reductase and they suggest that these activities likely played a prominent role in sulfur metabolism during evolution and may continue do so in modern cells as well. This also appears to be the first observation of catalase reductase activity independent of peroxide dismutation.