다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

We are just beginning to understand the metabolism of heavy metals and to use their metabolic functions in biotechnology, although heavy metals comprise the major part of the elements in the periodic table. Because they can form complex compounds, some heavy metal ions are essential trace elements, but, essential or not, most heavy metals are toxic at higher concentrations. This review describes the workings of known metal-resistance systems in microorganisms. After an account of the basic principles of homoeostasis for all heavy-metal ions, the transport of the 17 most important (heavy metal) elements is compared.

Microbial heavy-metal resistance

The brain is a singular organ of unique biological complexity that serves as the command center for cognitive and motor function. As such, this specialized system also possesses a unique chemical composition and reactivity at the molecular level. In this regard, two vital distinguishing features of the brain are its requirements for the highest concentrations of metal ions in the body and the highest per-weight consumption of body oxygen. In humans, the brain accounts for only 2% of total body mass but consumes 20% of the oxygen that is taken in through respiration. As a consequence of high oxygen demand and cell complexity, distinctly high metal levels pervade all regions of the brain and central nervous system. Structural roles for metal ions in the brain and the body include the stabilization of biomolecules in static (e.g., Mg2+ for nucleic acid folds, Zn2+ in zinc-finger transcription factors) or dynamic (e.g., Na+ and K+ in ion channels, Ca2+ in neuronal cell signaling) modes, and catalytic roles for brain metal ions are also numerous and often of special demand.

Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

Reactive oxygen species

What makes a heavy metal resistant bacterium heavy metal resistant? The mechanisms of action, physiological functions, and distribution of metal-exporting proteins are outlined, namely: CBA efflux pumps driven by proteins of the resistance–nodulation–cell division superfamily, P-type ATPases, cation diffusion facilitator and chromate proteins, NreB- and CnrT-like resistance factors. The complement of efflux systems of 63 sequenced prokaryotes was compared with that of the heavy metal resistant bacterium Ralstonia metallidurans. This comparison shows that heavy metal resistance is the result of multiple layers of resistance systems with overlapping substrate specificities, but unique functions. Some of these systems are widespread and serve in the basic defense of the cell against superfluous heavy metals, but some are highly specialized and occur only in a few bacteria. Possession of the latter systems makes a bacterium heavy metal resistant.

Efflux‐mediated heavy metal resistance in prokaryotes

All of the members of this family are thought to facilitate zinc efflux from the cytoplasm either into various intracellular compartments (endosomes, secretory granules, synaptic vesicles, Golgi apparatus, or trans-Golgi network) or across the plasma membrane. Thus, these transporters are thought to help maintain zinc homeostasis and facilitate transport of zinc into specialized intracellular compartments. Counterparts of the SLC30 family are found in all organisms. Most of the members of this class are predicted to have 6 transmembrane domains with both N- and C-termini on the cytoplasmic side of the membrane. Expression of rodent Znt1, Znt2 or Znt4 cDNAs in mammalian cells can confer resistance to zinc toxicity. Loss of function of the mouse Znt1 is embryonic lethal, loss of mouse Znt3 prevents accumulation of zinc in synaptic vesicles, nonfunctional mouse Znt4 (lethal milk) results in zinc-deficient milk, and Znt5-null mice display bone abnormalities and heart failure. No mutations in human counterparts of any of the members of the SLC30 family have been described.

Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers.

We have identified the gene responsible for the inherited zinc deficiency in the lethal milk (lm) mouse. The gene, here designated Znt4, encodes a 430-amino-acid protein that is homologous to two proteins, ZnT2 and ZnT3, responsible for sequestration of zinc into endosomal/lysosomal compartments and synaptic vesicles, respectively. We show that the Znt4 gene confers zinc resistance to a zinc-sensitive yeast strain and that it is abundantly expressed in the mammary epithelia and brain. The lethal milk mutant has a nonsense mutation at arginine codon 297 in the Znt4 gene.

Liping Huang

Papers

Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers.

A novel gene involved in zinc transport is deficient in the lethal milk mouse

The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles.

ZnT7, a Novel Mammalian Zinc Transporter, Accumulates Zinc in the Golgi Apparatus

Functional Characterization of a Novel Mammalian Zinc Transporter, ZnT6