Plasma protein ceruloplasmin

Factor IXa causes a rapid activation of factor X only if Ca2+, phospholipid,553 554 and the accessory factor Villa555 are present. The IXa Villa complex acts on X about 2 x 105 times faster than does IXa alone. This complex cleaves the same bonds in X as does the VIIa Va complex formed in the tissue factor pathway.514 The 2332-residue factor VIII and factor V have similar structures that include three repeats of a domain homologous to the blue copper-containing plasma protein ceruloplasmin (Chapter 16).556-559 Tyrosine 1680 of VIII apparently must be converted to a sulfate ester for full activity.560... 

Antioxidant Functions, Both intracellular and extracellular SODs are copper- and zinc-containing enzymes, able to convert superoxide radicals to hydrogen peroxide, which can be subsequently removed by catalase and other antioxidant defenses. The plasma protein ceruloplasmin also binds copper ions and thus prevents oxidative damage from free copper ions, which can generate hydroxyl radicals. 

Table 50-2 summarizes the functions of many of the plasma proteins. The remainder of the material in this chapter presents basic information regarding selected plasma proteins albumin, haptoglobin, transferrin, ceruloplasmin, aj-antitrypsin, aj i roglobulin, the immunoglobulins, and the complement system. The lipoproteins are discussed in Chapter 25. 

Ceruloplasmin Binds Copper, Low Levels of This Plasma Protein Are Associated With Wilson Disease... 

Most of the drugs are transported bound to nonspecific sites on plasma proteins, mostly to albumin (for acidic drugs) and to a -acid glycoprotein (for basic drugs). Binding to other proteins like ceruloplasmin and transcortin generally occurs to a much smaller extent. The binding is usually reversible and depends on the individual compound. 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

Dominant Role of the Liver in Biosynthesis of the Plasma Proteins with Special Reference to the Plasma Mucoproteins (Seromucoid), Ceruloplasmin, and Fibrinogen... 

Thrombin (MW 39,000) is a proteolytic enzyme of the serine protease group. It is derived from prothrombin, a circulating plasma protein, through the proteolytic action of a complex consisting of the proteolytic enzyme factor X (or factor Xa), another protein called factor V (accelerator protein), calcium, and phospholipid. Factor V has recently been identified as the plasma copper protein ceruloplasmin or a similar protein (see Chapter 6). 

The specific interaction of Cibacron Blue and its derivatives to dinucleotides, mainly to NAD, NADP and ATP offers the possibility of purifing all enzymes which are dependent on these coenzymes. According to Mosbach < - > there are 163 enzymes requiring NAD, 141 enzymes requiring NADP, about 40 enzymes requiring NADP or NAD and 225 enzymes dependent on ATP. Besides these specific interactions non-specific interactions of Cibacron Blue and its derivatives with. proteins can also be applied for separation purposes. The non-specific interaction of Cibacron Blue with human serum albumin, for instance, enables albumin to be removed from transferrin, ceruloplasmin or other plasma proteins in order to purify human... 

These are metal-binding proteins. A P-globulin, termed transferrin is capable of combining witii iron, copper and zinc. This protein constitutes approximately 3% of tire total plasma protein. Another example is ceruloplasmin, which contains copper. 

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. 

A second iron-transport system may be used by various cells. This system is thought to involve ceruloplasmin, a small peptide, and a membrane-bound transporter. A fraction of the iron in the bloodstream occurs, in the ferrous form, boimd to a small peptide. Ceruloplasmin is a plasma protein that can catalyze the oxidation of ferrous iron to ferric iron. Evidence suggests that the ceruloplasmin in the bloodstream catalyzes the oxidation of iron, and the coincident transfer of the iron... 

If one had to state an overall role of copper in the body, one might say oxygen metabolism. One major factor shared by both zinc and copper is that both metal ions occur bound to metallothionein. The function of metallothionein is not firmly established. Copper is bound to another protein, ceruloplasmin, which occurs in the cell and plasma. The function of this protein is not clear either. Zinc absorption, as iron absorption, is impaired by high levels of phytic acid. Copper absorption is not inhibited by phytic acid. The major route of excretion of both metal ions is fecal, rather than urinary. 

The most commonly submitted samples for direct trace element analysis are of whole blood, blood plasma, or serum. Plasma protein levels of the relevant carrier proteins transferrin (Fe), albumin (Zn), ceruloplasmin (Cu), and selenoprotein P (Se) can give useful additional information. 

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. ... 

Plasma Cu levels in rats are low at birth and increase sharply after postnatal day 10, concomitantly with the Cu storage protein ceruloplasmin. In contrast, plasma Zn levels were highest at birth and decreased slowly to adult values [26]. Older rats (20-22 months) have also been shown to have lower total plasma Fe content than middle aged rats (8-10 months), in addition to lower levels of the Fe-containing protein, hemoglobin [27]. 

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