Redox biochemistry of mammalian metallothioneins

TY - JOUR

T1 - Redox biochemistry of mammalian metallothioneins

AU - Maret, Wolfgang

PY - 2011/10

Y1 - 2011/10

N2 - Metallothionein (MT) is a generic name for certain families of structurally rather variable metal-binding proteins. While purely chemical or biological approaches failed to establish a single physiologic function for MTs in any species, a combination of chemical and biological approaches and recent progress in defining the low but significant concentrations of cytosolic free zinc(II) ions have demonstrated that mammalian MTs function in cellular zinc metabolism in specific ways that differ from conventional knowledge about any other metalloprotein. Their thiolate coordination environments make MTs redox-active zinc proteins that exist in different molecular states depending on the availability of cellular zinc and the redox poise. The zinc affinities of MTs cover a range of physiologic zinc(II) ion concentrations and are modulated. Oxidative conditions make more zinc available, while reductive conditions make less zinc available. MTs move from the cytosol to cellular compartments, are secreted from cells, and are taken up by cells. They provide cellular zinc ions in a chemically available form and participate in cellular metal muffling: the combination of physiologic buffering in the steady state and the cellular redistribution and compartmentalization of transiently elevated zinc(II) ion concentrations in the pre-steady state. Cumulative evidence indicates that MTs primarily have a redox-dependent function in zinc metabolism, rather than a zinc-dependent function in redox metabolism.

AB - Metallothionein (MT) is a generic name for certain families of structurally rather variable metal-binding proteins. While purely chemical or biological approaches failed to establish a single physiologic function for MTs in any species, a combination of chemical and biological approaches and recent progress in defining the low but significant concentrations of cytosolic free zinc(II) ions have demonstrated that mammalian MTs function in cellular zinc metabolism in specific ways that differ from conventional knowledge about any other metalloprotein. Their thiolate coordination environments make MTs redox-active zinc proteins that exist in different molecular states depending on the availability of cellular zinc and the redox poise. The zinc affinities of MTs cover a range of physiologic zinc(II) ion concentrations and are modulated. Oxidative conditions make more zinc available, while reductive conditions make less zinc available. MTs move from the cytosol to cellular compartments, are secreted from cells, and are taken up by cells. They provide cellular zinc ions in a chemically available form and participate in cellular metal muffling: the combination of physiologic buffering in the steady state and the cellular redistribution and compartmentalization of transiently elevated zinc(II) ion concentrations in the pre-steady state. Cumulative evidence indicates that MTs primarily have a redox-dependent function in zinc metabolism, rather than a zinc-dependent function in redox metabolism.

KW - Metallothionein

KW - Thionein

KW - Thiol reactivity

KW - Oxidoreduction

KW - Zinc(II) ions

KW - NULL MICE

KW - ZN-METALLOTHIONEIN

KW - OXIDATIVE STRESS

KW - II GENES

KW - LYSINE METHYLTRANSFERASE

KW - COORDINATION SITES

KW - BUFFERING CAPACITY

KW - ZINC-DEFICIENCY

KW - CELLULAR ZINC

KW - PROTEINS

U2 - 10.1007/s00775-011-0800-0

DO - 10.1007/s00775-011-0800-0

M3 - Literature review

SN - 0949-8257

VL - 16

SP - 1079

EP - 1086

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

IS - 7

M1 - N/A

ER -