29
Cu
Copper
63.55
Essential:
most Bacteria, Archaea, Eukarya
Copper
Environmental and health impacts:
-Cu deficiency leads to Fe deficiency in many organisms
-Defects in Cu homeostasis in Wilson’s and Menkes’ diseases
Reduce:
-Substitute Cu methane monooxygenase with Fe form (methanotrophs) (2)
-Substitute Cu-containing Cyt c oxidase with non-Cu oxidase (Pae; some fungi) (3)
-Substitute / replace CuZnSOD with MnSOD (fungi, Cre) (4)
-Substitute plastocyanin with heme-containing cytochrome c6 (cyanobacteria, Cre) (5)
Learn More!
(1) Copper: A Versatile Redox Cofactor
Cu is found as a cofactor in all kingdoms of life, where it is particularly useful as a catalyst of redox reactions, such as in electron transfer proteins azurin and plastocyanin, and reactions involving O2 chemistry, such as in hemocyanin for binding of O2 for transport (Crichton and Pierre, 2001). The catalytic potential of Cu is similar to that of Fe, except that more positive midpoint potentials are possible with Cu, compatible with reactions involving molecular O2. The evolution of cuproenzymes is believed to have occurred more recently than that of Fe-containing enzymes.
(2) Substituting Cu Methane Monooxygenase with Fe Form
In methanotrophs, a bacteria that uses methane as their carbon source, the first step in the aerobic methane oxidation pathway is the generation of methanol. This step is catalyzed by methane monooxygenase, which has two variations: a Cu-containing form associated with membranes and an Fe-containing form that is soluble.
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The Cu form is the more prevalent enzyme found in methanotrophs in both the alpha and gamma proteobacteria clades, but a few methanotrophs (including marine and freshwater species) have both forms (Murrell et al., 2000; Nakamura et al., 2007). The expression of one or the other is dependent on the Cu nutrition status (Murrell et al., 2000; Hakemian and Rosenzweig, 2007). The di-iron enzyme is expressed when there is low Cu in the growth medium while the Cu enzyme is expressed when there is an adequate supply of Cu.
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This regulated enzyme substitution has been documented in many different species. The Cu enzyme is presumed to be the preferred form because of the higher redox potential of Cu, with the Fe enzyme serving as a backup for this critical step in methane metabolism. The methanotrophs that express the backup Fe form have lower Cu requirements for growth (Graham et al., 1993; Hanson and Hanson, 1996).
(3) Substituting Cu-containing Cyt c Oxidase with non-Cu Oxidase
The loss of Cyt oxidase in Cu-limited cultures of bacteria and fungi is well documented (Gabel et al., 1994). Cu is a key element for aerobic respiration. In P. aeruginosa, it has been noted that aerobic respiration requires one of four different terminal oxidases (Frangipani et al., 2008). Three operons encode paralogous cytochrome c oxidases of the heme–Cu superfamily. A fourth cytochrome bd-type cyanide-insensitive oxidase lacks Cu in its active site. When P. aeruginosa is grown in the absence of Cu or in the presence of strong Cu chelators, growth is only possible if the Cu-free oxidase is present. Moreover, synthesis of the Cu-free oxidase is strongly induced by Cu depletion, although this seems to be an indirect effect mediated by the failure of the Cu-dependent enzymes to function.
(4) Substituting CuZnSOD with MnSOD
In fungi, in Cu-deficient cells, CuZnSOD synthesis was reduced, and its activity was replaced by induced synthesis of a nonmitochondrial MnSOD (Shatzman and Kosman, 1979). Comparison of Cu-dependent SOD activity in deficient versus replete cells indicated that 83% of total SOD activity is attributed to the CuZn enzyme in replete cells versus 17% in the deficient cells. This Cu-sparing mechanism allows maintenance of the Cyt oxidase levels independent of Cu nutrition status.
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As a permanent adaptation to long-term Cu deficiency, C. reinhardtii uses an FeSOD in the chloroplast, which can be supplemented with a MnSOD in Fe-deficient cells, plus MnSODs in the mitochondria and cytosol instead of CuZnSOD.
(5) Substituting Plastocyanin with Heme-Containing Cytochrome c6
Plastocyanin is a blue copper protein that catalyzes the transfer of electrons from the Cyt b6f complex to PS I during photosynthesis. A soluble c-type cytochrome (Cyt c6) can cover its function in many green algae and cyanobacteria. The synthesis of plastocyanin (Cu) and Cyt c6 (Fe) was found to be reciprocally dependent on Cu nutrition in both cyanobacteria and green algae. The signal transduction pathway responsible for the switch between plastocyanin and Cyt c6 was shown in C. reinhardtii to respond directly to Cu (Merchant and Bogorad, 1987).
(6) Recycle Cu from CuZnSOD to Cyt oxidase
In fungi, CuZnSOD is replaced with MnSOD. This Cu-sparing mechanism allows maintenance of the Cyt oxidase levels independent of Cu nutrition status. As the deficient cells divide and further deplete the Cu pools, only Cyt oxidase is maintained, which may occur by degradation of CuZnSOD and recycling of the constituent Cu.
(7) Degradation of Plastocyanin to Supply Cytochrome Oxidase
In C. reinhardtii, CRR1 controls all known responses to Cu deficiency, including plastocyanin degradation (Eriksson et al., 2004). The replacement of plastocyanin by Cyt c6 serves to spare Cu. Degradation of plastocyanin is important for Cu recycling as evidenced by the growth phenotype of crr1 mutants, which cannot maintain Cyt oxidase because they cannot recycle Cu from plastocyanin.