Heme-copper oxygen reductases (HCOs): membrane bound enzymes that reduce dioxygen to water coupled to translocation of protons across the membrane promoting charge separation and proton translocation. These are the last enzymes in the respiratory electron transport chain of aerobic organisms. During catalysis, four protons from the inner aqueous phase are uptaken to make water and up to four additional protons are translocated across the membrane, contributing to establish a transmembrane difference of proton electrochemical potential that the ATP synthase uses to synthesize ATP. Members of the heme-copper oxygen reductase superfamily are characterized by having in the catalytic subunit (subunit I) a low-spin heme, a binuclear center composed of a high-spin heme and a copper ion (CuB) and a catalytic tyrosine residue cross-linked to one of the histidine ligand of CuB.

Cytochrome c oxidase: A heme-copper oxygen reductase that receive electrons from a soluble cytochrome c.

Quinol oxidase: A heme-copper oxygen reductase that receive electrons from a quinol.

Binuclear center: Catalytic center of heme-copper oxygen reductases where the reduction of oxygen to water occurs. It is composed of a high-spin heme and a copper ion (CuB)

Catalytic tyrosine: Tyrosine residue, present in subunit I, cross-linked to a histidine ligand of CuB. It is proposed to be the source of the extra electron necessary for the complete reduction of O2. It is consider a distinct marker between HCOs and NORs.

Nitric oxide reductase (NORs): Membrane enzyme that catalyses the reduction of nitric oxide to water and N2O. Its catalytic subunit contains a low-spin heme and a binuclear center composed of a high-spin heme and an iron ion. The catalytic tyrosine is absent from all NORs known so far.

Charge separation: A result of the reaction catalyzed by HCOs in which the charges of opposite signs (e or H+) needed for the reaction are uptaken from different sides of the membrane.

Proton translocation: The ability of HCOs to pump protons from one side to the other side of the membrane contributing to the establishment and maintance of a difference of transmembrane electrochemical potential

High-spin heme: A heme that can be five or six-coordinated to a weak 6th ligand. According to the ligand field theory, if the energy required to pair two electrons in a t2g orbital is greater than the energy cost of placing an electron in an eg orbital, (small split between the eg and t2g orbitals) a high-spin split occurs and a high-spin heme is formed.

Low-spin heme: A heme that is strongly coordinated to a 6th ligand. According to the ligand field theory, if the energy required to pair two electrons in a t2g orbital is smaller than the energy cost of placing an electron in an eg orbital, (large split between the eg and t2g orbitals) a low-spin split occurs and a low-spin heme is formed.

A1 Type enzymes: HCOs with two proton-conducting channels, a D- and a K-channel. The presence of a glutamate residue in the D-channel is the fingerprint of these enzymes. These are the most widespread and best studied HCOs, being present in the three domains of life. The proton translocation stoichiometry is 1H+/e.

A2 Type enzymes: HCOs with two proton-conducting channels, a D- and a K-channel. The glutamate residue of the D-channel characteristic of A1 type enzymes is absent and is replaced by a tyrosine and a serine residue (YS motif) which is the fingerprint of these enzymes. These enzymes, with one exception are only present in the Bacteria domain. The proton translocation stoichiometry is 1H+/e.

B Type enzymes: HCOs with only one proton-conducting channel, an alternative K-channel. These enzymes are present in the Bacteria and Archaea domain and the few reports on their proton translocation activity indicate a ratio between 0.5-0.75 H+/e.

C Type enzymes: HCOs with only one proton-conducting channel, an alternative K-channel that is different from the K-channel of B Type enzymes. These enzymes are only present in the Bacteria domain and the few reports on their proton translocation activity indicate a stoichiometry between 0.2-0.4 H+/e.

Alternative oxidase (AOX): enzyme that catalyze the reduction of oxygen to water. Evolutionary unrelated to HCOs and not included in this study.

bd oxidase: enzyme that catalyze the reduction of oxygen to water. Evolutionary unrelated to HCOs and not included in this study.