Iron protein , serum

A recent report by Lovenberg and McCarthy 170) showed that in the presence of two-mercaptoethanol, sodium sulfide, and ferrous amonium sulphate, bovine serum albmnin will bind from 8 to 10 atoms of iron per mole of protein and an equivalent amount of acid labile sulfur. The optical spectrum of this compound is similar to that for the non-heme iron proteins. However, no biological or chemical reactivity related to ferredoxin has been observed. 

The iron-binding protein of serum transferrin was found in fraction IV-3,4 of human plasma when the plasma was fractionated by low temperature ethanol fractionation procedures (31, 116). By further subfractionations, serum transferrin could be concentrated in Cohn fraction IV-7 (30, 125, 126). Cohn (30) first reported the properties of the isolated protein, which he called the 3i metal-binding protein since the protein had been found to bind copper, and possibly zinc, as well as iron. Holm-berg and Laurell (66) proposed that the protein be called transferrin on the basis that the principal function of the protein was associated with the transport of iron in serum and that it was not the major copperbinding protein in human serum. 

Jandl, J. H., J. K. Inman, R. L. Simmons, and D. W. Allen Transfer of iron from serum-iron-binding protein to human reticulocytes. J. Clin. Invest. 38, 161 (1959). 

In one of the reports from this laboratory, we reported that an artificial non-heme iron protein synthesized from serum albumin displays... 

Fig. 13 indicates spectra of various samples of serum albumin treated with 2-mercaptoethanol or ferrous salt, or both. The sample treated with 2-mercaptoethanol alone contains no iron and no labile sulfur, whereas the sample treated with ferrous salt alone contains iron but not labile sulfur. Further, the sample treated with both 2-mercaptoethanol and ferrous salt exhibits a visible absorption and it contains 81.3 mp.-atoms of iron per mg of protein and 82.4 mjxmoles of labile sulfur per mg of protein. The spectrum of methylene blue derived from labile sulfur in the artificial iron protein by Lath s reaction is identical with that derived from a standard solution of Na2S or from native adrenodoxin. 

Fig. 13. Absorption spectra of artificial non-heme iron protein (61). Curve A serum albumin treated with 2-mercaptoethanol curve B serum albumin treated with ferrous ammonium sulfate curve C synthesized non-heme iron protein from serum albumin, treated with both 2-mercaptoethanol and ferrous ammonium sulfate...

Transferrin is a reversible iron-binding protein used in vertebrate iron-transport see Iron Proteins for Storage Transport their Synthetic Analogs). Manganese will bind to transferrin in vitro to form a Mn -transferrin complex. Transferrin appears to bind the majority of the serum Mn and may be important in Mn transport. 

An epidemiological study in a Finnish population indicated an association between moderate iron overload (measured by serum ferritin see Iron Proteins for Storage Transport their Synthetic Analogs) and increased incidence of coronary heart disease. This remarkable association has not been coirfirmed and further investigation will be necessary to determine whether excessive iron storage may relate to coronary heart disease. ... 

The relationship is not entirely linear because a small portion of iron in serum is bound to other proteins. Therefore the calculated TIBC values are sHghtiy higher than the amount of transferrin-bound iron. These small differences, however, are of no practical consequence. Immunoassays are available for assay of serum transferrin concentration. Results of the immunological measurement of transferrin concentration correlate with those of the TIBC assay. A slight advantage for the immunoassay of transferrin is that the required volume per specimen is much smaller. 

An indirect measurement of the iron-binding capacity of serum transferrin, the TIBC evaluation is performed by adding an excess of iron to plasma to saturate all transferrin with iron. The excess (unbound) iron is then removed and the serum iron concentration is determined. Unlike the serum iron level, the TIBC does not fluctuate over hours or days. The finding of a low serum iron level and a high TIBC indicates IDA. The TIBC is actually a measurement of the protein serum transferrin, which can be affected by a variety of factors. Patients with infection, malignancy, inflammation, liver disease, and uremia may have a decreased TIBC and a decreased serum iron level, which is consistent with the diagnosis of ACD. Oral contraceptive use and pregnancy can increase TIBC because the serum transferrin production is increased with a variety of other proteins. 

In the normal state, serum transferrin is about one third saturated with iron, 11-32 (tmol iron/liter serum (65-175 (xg/dL), with a normal total iron-binding capacity of 45-80 xmol/liter (250-450 jig/dL). About 10% of the transferrin molecules are saturated with iron at both sites, 45% have iron at either site, and 45% are free of iron [10]. The protein is usually measured on the basis of its iron-binding capacity, as will be discussed in Sec. 4, but immunoassays are also available for directly measuring serum transferrin protein concentration (36-61 p,mol/liter 2.52-4.29 g/liter). It is elevated in iron deficiency anemia, pregnancy, and acute hepatitis and decreased in chronic disease, nephrotic syndrome, and malignancies. 

A major contribution of the free-radical scavenging activity in blood plasma is attributable to the macro-molecular proteins (Wayner et al., 1985) of which albumin is a primary component and trapping agertt (Holt et al., 1984). Serum sulphydryl levels, primarily albumin-related, are decreased in subjects with rheumatoid complicated coalworkers pneumoconiosis, indicative of exacerbated inflammatory R.OM production (Thomas and Evans, 1975). Experimental asbestos inhalation in rats leads to an adaptive but evidendy insufficient response by an increase in endogenous antioxidant enzymes (Janssen etal., 1990). Protection of the vascular endothelium against iron-mediated ROM generation and injury is afforded by the iron sequestiant protein ferritin (Balia et al., 1992). 

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

Decreased red blood cell (RBC) count, hemoglobin (Hgb) and hematocrit (Hct) iron metabolism may also be altered [iron level, total iron binding capacity (TIBC), serum ferritin level, and transferrin saturation (TSAT)]. Erythropoietin levels are not routinely monitored and are generally normal to low. Urine positive for albumin or protein. 

Serum ferritin Less than 1 0-20 mcg/L (22-44 pmol/L) Ferritin is the protein-iron complex found in macrophages used for iron storage low in iron-deficiency anemia. 

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