30
Zn
Zinc
65.39
Essential: all life
Zinc
Environmental and health impacts:
-Can limit primary productivity in marine systems (P/Zn co-limitation; cofactor for carbonic anhydrase)
-Deficiency is a significant human health problem
Reduce:
-Substitute Zn-containing r-proteins for non-Zn proteins (2)
-Substitute non-Zn for Zn enzymes;
FolE2 for FolE1 (Bsu); DksA2 for DksA1 (Pae); many others (3)
-Substitute Co or Cd carbonic anhydrases for Zn-CA (T. weissflogii) (4)
-Substitute Ca alkaline phosphatases for Zn enzyme (5)
Learn More!
(1) Zinc: Essential for All Life
Zinc is an essential element for life and, unlike Fe, there are no known examples of organisms that have completely dispensed with a Zn requirement. Zn is not redox active under biological conditions, and it serves as an electrophilic catalyst (Lewis acid) in numerous enzymes and as a scaffold for organizing protein domains, especially in eukaryotes with the proliferation of Zn-finger proteins.
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Zn has many different roles, so cells have evolved complex responses to acclimate to Zn deprivation. The major common mechanisms involve increased uptake of Zn, the synthesis of alternative, Zn-independent enzymes and proteins (where possible), and the mobilization of intracellular Zn.
(2) Substituting C- for C+ r-proteins in B. subtilis
Ribsomes are highly abundant in growing cells and it is estimated that they contain 50% or more of the cellular Zn quota. Under conditions of Zn limitation, Zn-containing (C+) r-proteins can be replaced by their non-Zn-containing (C-) counterparts (Panina et al., 2003). The molecular basis of this protein switch is the derepression of the ytiA gene, which is a member of the Zur regulon, a Fur-like regulator for Zn homeostasis in B. subtilis (Nanamiya et al., 2004).
(3) Substituting non-Zn for Zn Enzymes
Synthesis of Zn-dependent isozymes is both an adaption mechanism to chronically low Zn environments and an acclimation mechanism in response to low Zn nutrition.
Substitute FolE2 for FolE1 (Bsu):
Zn activation of GTP cyclohydrolase (GCYH-IA) is sensitive to cellular Zn depletion and the resulting inability to synthesize folate, which is essential for synthesis of dTMP and other key metabolites, imposes a growth restriction. One evolutionary solution to this elemental limitation has been the emergence of an alternative isozyme (GCYH-IB) that relies instead on a different metal ion. The GCYH-IB isozyme is regulated by Zur and is induced by Zn limitation; it can function with various other divalent metal ions, including Mg (Sankaran et al., 2009).
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Substitute DksA2 for DksA1 (Pae):
P. aeruginosa encodes two genes encoding DksA, an RNA polymerase-binding transcription factor involved in the stringent response. One, DksA1, contains an essential Zn ion bound to four Cys residues. Under conditions of Zn limitation, induction of a Zur-regulated isozyme (DksA2) lacking associated Zn enables the cell to replace DksA function with a non-Zn-dependent protein (Blaby-Haas et al., 2011).
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(4) Substituting Co/Cd Carbonic Anhydrases for Zn-CA
Carbonic anhydrases, which catalyze the interconversion of CO2 and bicarbonate, are critical enzymes in carbon acquisition of aquatic phototrophs, and they are, accordingly, important for productivity (Cannon et al., 2010). Zn ion is the usual catalyst in carbonic anhydrases. In a Zn-deficient environment, the usual enzyme in the diatom Thalassiosira weissflogii (TWCA1) is replaced by a Cd-containing isoform, CDCA1 (Lane and Morel, 2000). This enzyme is found in other diatoms and is stimulated by Cd availability.
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Co was also found to stimulate the growth of Zn-deficient T. weissflogii cells by replacing Zn with Co in the TWCA1 isoform (Yee and Morel, 1996). In the coccolithophore Emiliana huxleyi, Co may be even more effective than Zn as a cofactor in carbonic anhydrase (Xu et al., 2007). Thus, Co may also support photosynthesis in a Zn-deficient natural environment.
(5) Substituting Ca Alkaline Phosphates for Zn Enzyme
In marine systems, low Zn levels are also correlated with low P availability, which is problematic since alkaline phosphatase, a key P acquisition enzyme, is itself a Zn enzyme. To circumvent this Zn–P colimitation, many Prochlorococcus species contain a distinct Ca-dependent phosphatase, PhoX (Kathuria and Martiny, 2011).
(6) Recycling Zn from C+ r-proteins
In B. subtilis, under Zn limiting conditions, the metalloregulator Zur facilitates the displacement of surface-exposed large subunit r-proteins (L31 and potentially L33), which releases substantial Zn for recycling into other target proteins (Nanamiya and Kawamura, 2010).
(7) Zn Storage in Eukarya
In S. cerevisiae, when Zn is relatively abundant, Zn uptake is mediated by the Fet4 transporter (which also imports Fe) and Zrt2, a representative of the ZIP family of transporters that are conserved throughout all three domains of life. Under Zn-replete conditions, import of excess Zn into the vacuole (up to 109 ions) provides a store for future use (Simm et al., 2007). When cells encounter Zn deficiency, high-affinity uptake systems are induced as is Zn mobilization from the vacuole (Bird, 2008; Eide, 2009). To enable mobilization of stored Zn, the metalloregulator Zap1 activates the expression of another ZIP transporter, Zrt3, that exports Zn stored in the vacuole.