Zinc metabolic disorder

Some reports found an increase in liver zinc concentrations in chronic liver disease. An increase in copper and zinc liver concentrations was found in Canadian children with chronic cholestasis (Phillips et al., 1996). Another case report described the increase in zinc concentration in hepatic tissue of a child with hepatosplenomegaly and symptoms of zinc deficiency, and the authors speculated about the existence of a zinc metabolism disorder (Sampson et al, 1997). A study that investigated the concentration of metals in liver tissue of adults with hereditary hemochromatosis found an increase in zinc in the liver parenchyma. The authors suggested that the concurrent increase in iron and zinc might be explained by the greater intestinal absorption of these metals (Adams et al., 1991). 

Zinc supplementation to these patients led to complete clearance of skin lesions and restoration of normal bowel function, which had previously resisted various dietary and drug regimens. This original observation was quickly confirmed in other cases with equally good results. The underlying mechanism of the zinc deficiency in these patients is most likely attributable to malabsorption. The cause of poor absorption is obscure, but an abnormality of Paneth s cells may be involved. These observations should provide a great stimulus to all interested in zinc metabolism to look for manifestations of zinc deficiency in other disorders, either natural or induced, in both children and adults. 

Cuajungco MP, Lees GJ. Zinc metabolism in the brain relevance to human neurodegenerative disorders. Neurobiol Dis 1997 4 137-69. 

In this section, I list diseases and conditions known to cause or accompany magnesium deficiency. My purpose is to show you that one disease can cause others by creating deficiencies that open up a person to other diseases.The following conditions are known to contribute to magnesium deficiency Bartter s syndrome bile insufficiency celiac disease bowel infections vomiting diarrhea alcoholism diabetes high levels of diuretics, vitamin D, or zinc hyperthyroidism metabolic disorders hormone disorders fat metabolism problems colostomy and kidney dysfunctions. 

Zinc is found in all human tissues and all body fluids. The metal is essential for growth, development, and reproduction in man. Disorders of zinc metabolism are usually due to a deficiency rather than a surplus of zinc. 

Zinc deficiency in growing organisms leads to metabolic disorders. First, RNA synthesis ceases, after which protein, total nitrogen and DNA values decrease (Schneider and Price 1962). In Euglena the absolute quantity of RNA decreases when there is a serious deficiency of zinc (Price 1966). 

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). 

Acrodermatitis enteropathica is a metabolic disorder that results in the malabsorption of zinc. However, when patients afflicted with this disorder were treated with human milk, zinc absorption was enhanced (Lombeck et al. 1975). It was reported by Evans (1980) that patients with acrodermatitis enteropathica have an impaired tryptophan metabolic pathway. Picolinic acid, a chief metabolite of tryptophan, is also a constituent of human milk. Picolinic acid is secreted by the pancreas into the intestinal lumen. A study by Boosalis et al. (1983) demonstrated that patients with pancreatic insufficiency had difficulty absorbing zinc administered as zinc sulfate. However, when these pancreatic-insufficient patients were given zinc as zinc picolinate, the extent of zinc absorption was similar to that of healthy controls. Zinc absorption may depend on the bioavailability of picolinic acid. Such a mandatory role of picolinic acid in absorption has not been confirmed (Bonewitz et al. 1982). 

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... 

Zinc. Diabeticlike disorders of metabolism have been observed in zinc-deficient animals, but the btisis for this abnormality is not understood. 

Zinc and cadmium have an oxidation number of +2 in all their compounds. Zinc is an essential element for human health. It is present in many enzymes and plays a role in the expression of DNA and in growth. Zinc is toxic only in very-high amounts. However, cadmium is a deadly poison that disrupts metabolism by-substituting for other essential metals in the body such as zinc and calcium, leading to soft bones and to kidney and lung disorders. 

In many crucial biological processes, such as oxygen transport, electron transport, intermediary metabolism, metals play an important part. Therefore, disorders of metal homeostasis, metal bioavailability or toxicity caused by metal excess, are responsible for a large number of human diseases. We have already mentioned disorders of iron metabolism (see Chapter 7) and of copper metabolism (see Chapter 14). The important role, particularly of redox metals such as copper and iron, and also of zinc, in neurodegenerative diseases, such as Parkinson s disease, Alzheimer s disease, etc. has also been discussed (see Chapter 18). We will not further discuss them here. 

An excess of zinc will cause problems in humans. Excessive doses can lead to biochemical control system damage, while doses slightly higher than optimal can cause disorders in iron and copper metabolism, resulting in incurable anemia, decrease in activity of zinc protein enzymes, and pancreas and kidney damage (Boularbah et ah, 1999 Seiler et ah, 1994). Increased levels of zinc have been observed in nuclei of neoplastic cells and in cases of acute dental caries, however its role in these diseases has not been explained. 

Zinc is used for a variety of indications. Zinc acetate (8.102) or, rarely, zinc sulfate (8.103) have been used orally to treat Wilson s disease, a recessively inherited disorder of copper metabolism, characterized by brain and liver dysfunction arising from excessive deposits of copper. Zinc pyrithione (8.104) is used in shampoos to treat seborrhea. Zinc propionate (8.105) and zinc caprylate (8.106) have been used as topical antifungal agents. 

Subacute Zinc Defiency Subacute zinc deficiency is the major clinical zinc deficiency syndrome in the U.S. Based upon a national survey of smell function performed in 1980, estimates suggest that this syndrome may affect as many as 4 million people (59). The etiology of subacute zinc deficiency is related to a variety of disorders which do not, at first glance, appear to have any specific relationship to a metabolic disease process (Table III) (60). Indeed, the mechanisms by which a viral illness, head Injury, surgical procedures, or allergic rhinitis may produce lowered body zinc levels are still unknown. In addition, to complicate this problem further, the onset of this syndrome can occur relatively quickly, over days, or more slowly, over... 

The quinolones are contraindicated in patients with a history of hypersensitivity to any drug in this family. Absorption of the fluoroquinolones is reduced by antacids, iron, and zinc salts, and thus they should not be taken concurrently. Oral ciprofloxacin and enoxacin inhibit the metabolism of theophylline, and toxicity can occur when these two drugs are administered concurrently. Oral administration of the fluoroquinolones can cause convulsions and should therefore be done with caution in patients with central nervous system disorders. These drugs are not recommended for systemic administration in children, adolescents younger than age 18 years, or pregnant women. Topical administration is contraindicated for use in patients younger than 1 year of age. 

Because of their importance in many enzymes, bacteria have had to develop uptake systems for both copper and zinc. Copper uptake (and homeostasis, which is discussed in Chapter 8) has been extensively studied in the Gram-positive bacteria Enterococcus hirae. At the membrane, a reductase, indicated as R in Fig. 7.10, reduces Cu to Cu" " which is taken up by CopA when copper is limiting. In contrast, when copper is in excess, CopB extrudes excess copper. Both CopA and CopB belong to the PI subclass of P-type ATPases, which includes the proteins involved in the disorders of copper metabolism in humans, Mentke s, and Wilson s disease (discussed in Chapter 14). 

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