Copper metabolism disorders

Menkes disease ( kinky or steely hair disease) is a disorder of copper metabolism. It is X-hnked, affects... 

Wilson s disease A disorder of copper metabolism characterized by cirrhosis of the liver and neurologic manifestations a potentially fatal genetic disorder that causes the body to retain copper. 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

Creutzfeldt-Jakob and other prion diseases have been associated with disorders of copper metabolism. The first cases of Creuzfeldt-Jakob disease in humans were described by Creuzfeldt and Jakob over 80 years ago. Although scrapie was known as a fatal neurological... 

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. 

Metabolic disorders such as Wilson s disease (copper storage disease) and haemochro-matosis (iron overload disease),... 

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. 

Two genetic disorders of copper metabolism, Wilson s disease (see Section 62.2.3.3) and Menkes disease, are known. The latter involves impaired intestinal absorption of copper56,57 as well as probably subcellular metabolic defects which result in copper deficiency with respect to metal-loenzyme activity. The characteristic steely hair in Menkes disease results from free SH bonds in hair protein because of failure of lysyl oxidase to produce the disulfide links. Depigmentation of hair and skin, hypothermia, cerebral degeneration, central nervous system retardation, skeletal demineralization and arterial degeneration are all seen. Copper supplements may benefit hypothermia and increase pigmentation but the disease is not generally cured. 

Wilson s disease, an autosomally recessively inherited disorder, is due to a defect in copper metabolism which leads to an accumulation of the element in the liver. A subse-... 

D-Penicillamine 26 (Figure 2.8) has for long time been used for the treatment of Wilson s disease, a metabolic disorder in which absorbed copper is deposited mainly in the liver and in the brain. Long-term application of this compound leads to suppression of rheumatoid arthritis, which now is its main therapeutic use [3],... 

Caeruloplasmin Copper-incorporating a glycoprotein true function remains unclear but acts as a copper donor and oxidative enzyme Low caeruloplasmin levels may be seen in cirrhosis (especially primary biliary cirrhosis) as caeruloplasmin is excreted hepatically Levels increased in infection, injury or inflammation. Low levels are found in Wilson s disease, which is an autosomal recessive disorder of copper metabolism it results in copper deposition in the liver, basal ganglia and eyes, and culminates in cirrhosis and neurological impairment... 

Wilson s disease is an inherited disorder of copper metabolism. Copper accumulates initially in the liver and then in the nervous system, leading to severe liver and neurological disease. The retention of copper begins at birth, but it may take decades before the liver is sufficiently damaged... 

The copper content of this compartment is maintained by one or two P-type ATP-utilizing copper pumps. These two proteins are known by their association with two disorders of human copper metabolism, the Menkes (MNK) and Wilson (WND) proteins, and genetically as ATP7A and ATP7B, respectively (see Metal-related Diseases of Genetic... 

Menkes disease is another genetic disorder of copper metabolism characterized by an impairment in the absorption of dietary copper and severe disturbance in the intracellular... 

Severe alterations in copper metabolism occur in two genetic disorders, Wilson s disease and Menkes disease, both of these diseases arc rare and occur in about one in 100,000 birtKs. Both diseases involve naturally occurring mutations in copper transport proteins, i.e membrane-bound proteins that mediate the passage of copper ions through cell membranes. The copper transporters that are defective in these two diseases are not the same protein, but they are related. To express this relation in numbers, over half (57 a) of the sequence of amino adds, as they occur in the polypeptide chains, are identical. Both proteins are thought to utilize ATP to drive copper ions through membranes. 

The human hereditary disorders Wilson s disease and Menkes disease have provided further insight into copper metabolism. In Wilson s disease the ceruloplasmin content is low and copper gradually accumulates to high levels in the liver and brain. In Menkes syndrome, there is also a low ceruloplasmin level and an accumulation of copper in the form of... 

Wilson s disease is an autosomal recessive inherited disorder of copper metabolism resulting in accumulation of copper in various tissues. Rats raised to have a large accumulation of copper had 80 times greater concentration of MTs in their liver compared to controls (5016pgg vs. 65pgg ). 

Wilson s disease is an autosomal recessive disorder of copper metabolism (see Chapters 20 and 30). It has a gene frequency of 1 in 200 and a disease frequency of 1 in 30,000. It is due to one of more than 200 mutations in a gene on chromosome 13 coding for a copper transporting ATPase... 

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). 

Disorders of Copper Metabolism — Wilson s and Menkes Diseases and Aceruloplasminaemia... 

Other chronic disorders cause osteomalacia. " " Phosphate depletion from low dietary intake, phosphate-binding antacids, and oncogenic osteomalacia (potentially phosphaturic effect) can cause osteomalacia. Hypophosphatasia is an inborn error of metabolism in which deficient activity of alkaline phosphatase causes impaired mineralization of bone matrix. Acidosis from renal dysfunction, distal renal tubular acidosis, hypergammaglobulinemic states (e.g., multiple myeloma), and drugs (e.g., chemotherapy) compromises bone mineralization. Renal tubular disorders secondary to Fanconi s syndrome, hereditary diseases (e.g., Wilson s disease, a defect in copper metabolism), acquired disease (e.g., myeloma), and toxins (e.g., lead) cause osteomalacia to varying degrees. Chronic wastage of phosphorus and/or calcium limits mineralization, which may be further compromised by acidosis and secondary hyperparathyroidism. 

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