5. Excess: Fe overload can occur with accidental ingestion. [Note: Acute Fe poisoning is the most common cause of poisoning deaths of children age <6 years (UL = 40 mg/day for children, 45 mg/day for adults).] Treatment is use of an Fe chelator. Overload can also occur with genetic defects. An example is hereditary hemochromatosis (HH), an AR disorder of Fe overload found primarily in those of Northern European ancestry. It is most commonly caused by mutations to the HFE (high iron) gene. Hyperpigmentation with hyperglycemia (“bronze diabetes”) and damage to the liver (a major storage site for Fe), pancreas, and heart may be seen. In HH, serum Fe and Tf saturation are elevated. Treatment is phlebotomy or use of Fe chelators. [Note: Fe overload is seen with mutations to proteins of Fe metabolism that result in inappropriately low levels of hepcidin. It can result in hemosiderosis (the deposition of hemosiderin, an intracellular, insoluble storage form of Fe).]
C. Manganese
Mn is important for the function of several enzymes (Fig. 29.10). Whole grains, legumes (for example, beans and peas), nuts, and tea (especially green tea) are good sources of the mineral. Consequently, Mn deficiency in humans is rare. Toxicity from foods and/or supplements is also rare (UL = 11 mg/day for adults).
D. Zinc
Zn plays important structural and catalytic functions in the body. Zinc fingers are supersecondary structures (motifs, see p. 18) in proteins (for example, transcription factors) that bind to DNA and regulate gene expression (Fig. 29.11). Hundreds of enzymes require Zn for activity. Examples include alcohol dehydrogenase, which oxidizes ethanol to acetaldehyde (see p. 317); carbonic anhydrase, which is important in the bicarbonate buffer system (see p. 30); porphobilinogen synthase of heme synthesis, which is inhibited by lead (lead replaces the zinc; see p. 279); and the nonmitochondrial isoform of superoxide dismutase (SOD), which also requires Cu (see Fig. 29.5). Dietary sources of Zn include meat, fish, eggs, and dairy products. Phytates (phosphate storage molecules in some plant products) irreversibly bind Zn in the intestine, decreasing its absorption, and can result in a deficiency. [Note: Phytates may also bind Ca2+ and nonheme Fe.] Several drugs (for example, penicillamine) chelate metals, and their use may cause Zn deficiency. [Note: Severe deficiency is seen with a defect in the intestinal transporter for Zn that results in the malabsorption disorder acrodermatitis enteropathica. Symptoms include rashes, slowed growth and development, diarrhea, and immune deficiencies. Vision problems may also occur because Zn is needed in the metabolism of vitamin A.]
Eukaryotic cells infected with bacteria can restrict availability of the essential micronutrients Fe, Mn, and Zn to the pathogens. This decreases the intracellular survival of the pathogen and is known as “nutritional immunity.”
E. Other microminerals
Chromium (Cr) and fluorine (F) also play roles in the body. Cr potentiates the action of insulin by an unknown mechanism. It is found in fruits, vegetables, dairy products, and meat. F (as fluoride [F−]) is added to water in many parts of the world to reduce the incidence of dental caries (Fig. 29.12). F− replaces the hydroxyl group of hydroxylapatite, forming fluoroapatite that is more resistant to the enamel-dissolving acid produced by mouth bacteria.