Regulation of zinc metabolism

The absorption of dietary zinc occurs over the duodenal and jejunal regions of the gastrointestinal tract, and mainly follows via a saturable carrier-mediated transport process (Zapsalis and Beck 1985, Lee et al. 1989). The mechanism and control of zinc absorption from the intestine has not yet been fully elucidated, although absorption of zinc is known to be regulated homeostatically, mainly under the control of pancreatic and intestinal secretion and fecal excretion. Homeostasis may involve metal-binding proteins such as metallothionein and cysteine-rich intestinal protein. Metallothionein plays an essential role in the regulation of zinc metabolism (Richard and Cousins 1975, Petering and Fowler 1986). Other unknown mechanisms may also exist, and the uptake from intestinal mucosa may involve both active and passive transport processes. 

As discussed above, a wide range of much more common conditions may so disturb the regulation of zinc metabolism that a degree of secondary zinc depletion results. In these cases, the effects will be difficult to separate from those caused by the primary disease, but there is interest in the role of zinc in relation to cellular immunity (Good, 1981). Disorders of the speciai senses such as taste and smell are also linked to marginal zinc depletion (Russell et al., 1983). 

Cousins RJ, Leinart AS (1988) Tissue specific regulation of zinc metabolism and metallothionein genes by interleukin-1. FASEB J 2 2884-2890 Danks DM (1989) Disorders of copper transport. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) Metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 1411-1431... 

Cousins RJ, Blanchard RK, Moore JB et al. (2003) Regulation of zinc metabolism and genomic outcomes. Journal of Nutrition 133(5S-1) 1521S-1526S. 

Minerals include sodium, potassium, calcium, phosphorus, magnesium, manganese, sulphur, cobalt and chlorine trace minerals include iron, zinc, copper, selenium, iodine, fluorine and chromium. Their roles may be generalised within the areas of providing structure in the formation of bones and teeth, maintenance of normal heart rhythm, muscle contractility, neural conductivity, acid-base balance and the regulation of cellular metabolism through their activ-ity/structural associations with enzymes and hormones. The daily requirements of minerals can be obtained from a well-balanced diet. 

Wastney me, Aamodt RL, Rumble WF and Henkin RI (1986) Kinetic analysis of zinc metabolism and its regulation in normal humans. Am J Physiol 251 R398-R408. 

Andrews GK, Gallant KR, Cherian MG (1987) Regulation of the ontogeny of rat liver metallothionein mRNA by zinc. Eur J Biochem 166 527-531 Andrews GK, McMaster MT, De SK, Paria BC, Dey SK (1993) In Suzuki KT, Imura N, Kimura M (eds) Cell-specific expression and regulation of the mouse metallothionein I and II genes in the reproductive tract and preimplantation embryo. Metallothionein III. Birkhauser, Basel, pp 363-380 Bakka A, Webb M (1981) Metabolism of zinc and copper in the neonate changes in the concentration and contents of the thionein bound Zn and Cu with age in the livers of the newborn of various species. Biochem Pharmacol 30 721-725 Bremner I (1993) Involvement of metallothionein in the regulation of mineral metabolism. In Suzuki KT, Imura N, Kimura M (eds) Metallothionein III. Birkhauser, Basel, pp 111-124... 

Peroxisome proliferator-activated receptors (PPARs) PPREs Regulate multiple aspects of lipid metabolism Activated by fibrates and thiazolidinediones Zinc finger... 

The exact cause of Alzheimer s disease remains unknown, although a number of factors have been suggested. These include metabolism and regulation of amyloid precursor protein, plaque-related proteins, tau proteins, zinc, copper, and aluminum [1]. 

Leucine aminopeptidase (LAP, E.C.3.4.11.1) is one of the first discovered and the most widely studied aminopeptidase with respect to sequence, structure and mechanism of action.59 -63 LAP is a zinc containing exopeptidase that catalyzes the removal of amino acids from the N-terminus of peptides or proteins. Similar to other aminopeptidases, this enzyme is of significant biological and medical importance because of its key role in protein modification, activation, and degradation as well as in the metabolism of biologically active peptides and activity regulation of hormonal... 

Another common biomarker for trace metal exposure is the metal-binding protein metallothionein, which regulates normal zinc and copper metabolism and provides a mechanism for metal detoxification. Changes in metallothionein activity provide a sensitive marker of trace metal exposure. 

In this article, we will focus mainly on the mechanisms of iron and zinc regulation, because regulation of these two metals illustrates many basic principles. We will also reference reviews that address regulation of copper and manganese metabolism, but regulation of these metals will not be discussed in depth here, in part because they will be discussed elsewhere. 

Normalization of laboratory parameters must be guaranteed (i.) regulation of serum electrolytes, acid-base equilibrium and blood sugar values, (2.) substitution of zinc, and (2.) compensation of hypovolaemia. Metabolic alkalosis should not be balanced, since it is important for the urea cycle. 

Zinc is involved in many biochemical functions. Several zinc metal-loenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microoragnisms and is essential for DNA synthesis. Thymidine kinase, DNA-dependent RNA polymerase, DNA-polymer-ase from various sources, and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase, thus the catabolism of RNA appears to be zinc dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. 

This chapter discusses the pathways by which L-tryptophan is metabolized into a variety of metabolites, many of which have important physiological functions. A few metabolites are cited here briefly. Quinolinic acid is involved in the regulation of gluconeogenesis. Picolinic acid is involved in normal intestinal absorption of zinc. The body s pool of nicotinamide adenine dinucleotide (NAD) is influenced by L-tryptophan s metabolic conversion to niacin. Finally, L-tryptophan is the precursor of several neuroactive compounds, the most important of which is serotonin (5-HT), which participates as a neurochemical substrate for a variety of normal behavioral and neuroendocrine functions. Serotonin derived from L-tryptophan allows it to become involved in behavioral effects, reflecting altered central nervous system function under conditions that alter tryptophan nutrition and metabolism. 

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