Ceruloplasmin hepatic synthesis

For hospital patients with infections, and after accidental injury or postsurgery, the systemic inflammatory response wiU affect the concentration of essential elements in circulating blood independently of nutritional status. For example, the APR causes increased permeability of capillaries and transfer of certain plasma carrier proteins and their trace metals into interstitial space. Hepatic synthesis of some plasma proteins, the so-called acute phase proteins, is also induced, so that these proteins increase in concentration in plasma, together with any metals that they carry (e.g., ceruloplasmin and copper). Moreover, there are marked changes in the kinetics of elements, with altered rates of transfer to and from the tissue. Knowledge of the effect of disease on metal kinetics and distribution is therefore essential. ... 

Another genetic defect results in failure of hepatic synthesis of ceruloplasmin (aceruloplasminemia), which is a neurodegenerative disease. Retinal damage, secondary iron overload, and insulin-dependent diabetes present in the fourth to fifth decade of life. ... 

Since about 90% of plasma copper is bound to ceruloplasmin, factors that increase the hepatic synthesis of ceruloplasmin, such as an APR or the oral contraceptive pill, will increase plasma copper independently of dietary copper intake. In premature infants with fiver immaturity and low ceruloplasmin synthesis, plasma copper values below 30 IXg/L (<5pmol Cu per L) suggest the necessity for increased copper input. 

High levels of zinc stimulate the synthesis of metallothionein in the small intestines. The elevated levels of metallothionein then serve as a depot for the binding of high levels of zinc consumed in subsequent meals. The induced protein has been shown to limit the amount of zinc entering the bloodstream with consumption of a high-zinc diet (Menard ef o/., 1981). High doses of copper can induce metallothionein synthesis to the same extent as can zinc. At levels near those found in the diet, zinc is a potent inducer while copper is only a weak inducer. Normally, hepatic metaiiothionein contains mainly zinc, whereas kidney metallothionein contains copper and, when present in the diet, cadmium. The copper entering the liver may be stored in hepatic metallothionein and released into the plasma in ceruloplasmin or secreted in the bile later. 

Zinc is relatively nontoxic. Nevertheless, high doses (1 g) or repetitive doses of 100 mg/day during several months may lead to disorders. Among these are gastrointestinal tract symptoms [56], a decrease in heme synthesis due to an induced copper deficiency, diminution of high-density lipoproteins (HDLs), hyperglycemia, reduction of serum ceruloplasmin and copper [57], and an increase of the intestinal and hepatic alkaline phosphatase activity. 

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