Important Cofactor In Many Biochemical Reactions

As a constituent of over 300 metalloenzymes, zinc is involved in myriad chemical reactions that are important for normal body functioning, such as carbohydrate metabolism, protein and DNA synthesis, protein digestion, bone metabolism and endogenous antioxidant systems (Beers et al 1999, Wahlqvist et al 1997, Wardlaw et al 1997). At the cellular level, the function of zinc can be divided into three categories: catalytic, structural and regulatory (King 2003).

Growth and development Zinc is important for the formation of biomembranes and zinc finger motifs found in DNA transcription factors (Semrad 1999).

Normal immune responses Zinc is involved in many aspects of immunological function. It is essential for the normal development and function of cells, mediating non-specific immunity such as neutrophils and natural killer cells and affecting development of acquired immunity and T-lymphocyte function. Deficiency rapidly diminishes antibody and cell-mediated responses in both humans and animals, leading to increases in opportunistic infections and mortality rates (Fraker et al 2000). Animal models have shown that suboptimal intake of zinc over 30 days can lead to 30-80% loss in defence capacity. Investigation using a human model has demonstrated that even mild deficiency in humans adversely affects T-cell functions (Prasad 1998). Conversely, high-dose zinc supplementation (20-fold RDI) can also produce immune dysfunction.

Neurological function Zinc ions are unevenly distributed in the CNS, acting as neurosecretory products or cofactors. Zinc is highly concentrated in the synaptic vesicles of specific neurons, known as 'zinc-containing' neurons (Frederickson and Danscher 1990, Frederickson and Moncrieff 1994, Frederickson et al 2000). Zinc-containing neurons are a subset of glutamatergic neurons and mostly located in the telencephalon. Zinc is released from zinc-containing neurons in a calcium- and impulse-dependent manner, producing a broad spectrum of neuromodulatory effects. Additionally, zinc appears to stabilise the storage of certain macromolecules in presynaptic vesicles.

Reproduction In humans, zinc is necessary for the formation and maturation of spermatozoa, for ovulation, and for fertilisation (Favier 1992). Zinc has multiple actions on the metabolism of androgen hormones, oestrogen and progesterone, and these, together with the prostaglandins and nuclear receptors for steroids, are all zinc finger proteins.

In adult males, zinc content is high in the testis and prostate, which have the highest concentration of zinc of any organ in the body (Bedwal & Bahuguna 1994).

In women, zinc deficiency in pregnancy has been associated with increased maternal morbidity, increased risk of abortion, stillbirth, teratogenicity and other unwanted outcomes (Bedwal & Bahuguna 1994).

Antioxidant Zinc limits oxidant-induced damage in a number of indirect ways, such as protecting against vitamin E depletion, controlling vitamin A release, contributing to the structure of the antioxidant enzyme extracellular superoxide dismutase, restricting endogenous free radical production, maintaining tissue concentrations of metallothionein, a possible scavenger of free radicals, and stabilising membrane structure (DiSilvestro 2000). More recently it was observed to decrease Zinc 1385

lipid peroxidation, and protect mononuclear cells from TNF-alpha induced NF-kappa-B activation associated with oxidative stress (Prasad et al 2004). Insulin-like activity One of the in vivo features of zinc is its insulin-like function, which is mediated via inhibition of endogenous GSK-3 (llouz et al 2002). This is important because GSK-3 inhibition appears essential for normal function of the insulin-activated signalling pathway.

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