Zinc: Main Actions

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. At the cellular level, the function of zinc can be divided into three categories: catalytic, structural and regulatory.

Growth and development

Zinc is important for the formation of biomembranes and zinc finger motifs found in DNA transcription factors.

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. 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. 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. 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. Zinc has multiple actions on the metabolism of androgen hormones, oestrogen and progesterone, and these, together with the prostaglandinsand 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.

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

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. More recently it was observed to decrease lipid peroxidation, and protect mononuclear cells from TNF-alpha induced NF-kappa-B activation associated with oxidative stress. 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. This is important because GSK-3 inhibition appears essential for normal function of the insulin-activated signalling pathway.