28.8: Metallothionein concentrations in circulating blood cell types (24c.8)
- Page ID
- 117298
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Metallothionein is a small, cysteine-rich, metal-binding protein that readily binds to zinc and heavy metals. Up to seven zinc molecules can bind to one metallothionein molecule, that may serve as a small zinc reserve for cells. The highest concentrations of metallothionein are found in the liver, kidney, pancreas, and intestine. Concentrations in the intestine and pancreas respond to changes in dietary zinc intake, suggesting that metallothionein assists in the maintenance of zinc homeostasis in these tissues (King, 2011). Metallothionein also has a role in the acute phase response associated with inflammation when hepatic synthesis of metallothionein is activated, causing the redistribution of zinc from the plasma to the liver (Raiten et al., 2015).
Smaller quantities of metallothionein are also present in all tissue cells, and concentrations in serum, erythrocytes, and monocytes have been investigated as potential biomarkers of human zinc status. Serum metallothionein concentrations reflect changes in hepatic metallothionein, so any increase in hepatic levels in response to stress, inflammation etc., will result in concomitantly elevated levels in serum, thus limiting the use of serum metallothionein as a biomarker of zinc status.
In contrast to serum, erythrocyte metallothionein is not responsive to stress and appears to be sensitive to severe and moderate restrictions in dietary zinc intake, based on results of depletion-repletion studies (Grider et al., 1990; Thomas et al., 1992). However, because most of the metallothionein in erythrocytes is concentrated in the reticulocyte fraction, changes in erythropoiesis, as may occur with poor iron status, influence total erythrocyte metallothionein levels. With the advent of commercially available immunoassays for metallothionein, more research on the response of metallothionein concentrations in erythrocytes and other blood cell types to changes in dietary zinc intake or status in community-based studies is now possible. However, reference material for metallothionein concentrations is also needed to allow comparison of metallothionein concentrations using different immunoassays across studies (Hennigar et al., 2016). At present, the sensitivity and specificity of metallothionein concentrations in erythrocytes and other blood cell types and their usefulness in community-based studies remains to be established. As a consequence, metallothionein concentration in circulating blood cell types was classified as an “emerging” biomarker of zinc exposure and status by the BOND Zinc Expert Panel (King et al., 2015).