Transferrin is the physiologic carrier of iron through the plasma and extracellular fluid.15 Apotransferrin, transferrin without attached iron, is a single-chain glycoprotein with two structurally similar lobes. Binding of a ferric ion to one of these lobes yields monoferric transferrin; binding of ions to both yields diferric transferrin. The transferrin saturation is the proportion of the available iron-binding sites on transferrin that are occupied by iron atoms, expressed as a percentage. In humans, almost all the circulating plasma apotransferrin is synthesized by the hepato-cyte.17 After delivering iron to cells, apotransferrin is promptly returned to the plasma to again function as an iron transporter, completing 100 to 200 cycles of iron delivery during its lifetime in the circulation.
Cellular iron storage utilizes ferritin, a protein found in the cytoplasm of virtually all cells. Ferritin is a spherical shell that can store as many as 4,500 atoms of iron in its interior. Ferritin functions both as a safe storage site for iron and as a readily accessible reserve for iron that has been acquired by the cell in excess of its immediate needs.20 Accordingly, the greatest amounts of ferritin are found in cells dedicated to iron storage (e.g., macrophages and hepatocytes) and in cells with the highest iron requirements for the synthesis of iron-containing compounds (e.g., developing erythroid cells). Apoferritin, or ferritin without attached iron, is composed of 24 oblong subunits that are designated as H (heavy) and L (light). Ferritin molecules with a greater proportion of H subunits seem to be more active in iron metabolism; ferritin molecules with a greater abundance of L subunits apparently are used for the longer-term storage of iron. A ferritin H-like protein assembled into ferritin shells has been identified within iron-loaded mitochondria of patients with impairment of heme syn-thesis.21 In patients with sideroblastic anemia, most of the iron in ringed sideroblasts is sequestered in mitochondrial ferritin.22
Unconjugated Bilirubin (Bilirubin): water insoluble, must be extracted with EtOH prior to reaction with diazonium salts ---> Indirect Reaction ---> "" ---> a lot of Heme Metabolism
Remarkable progress continues to be made in understanding disorders of iron metabolism and in improving the diagnosis and management of both iron deficiency and iron overload.14,15 In the body, iron transports and stores oxygen, carries electrons, catalyzes reactions in oxidative metabolism, and sustains cellular growth and proliferation. With iron deficiency, the body is unable to produce sufficient amounts of heme, other iron-por-phyrin complexes, metalloenzymes, and other iron-containing compounds to sustain normal functions. With iron overload, excess iron can catalyze free radical reactions that can damage cellular membranes, proteins, and nucleic acids, resulting in progressive cellular and organ damage and eventual death.
The concentration of iron in the human body is carefully regulated and is normally maintained at about 40 mg Fe/kg in women and about 50 mg Fe/kg in men. Iron balance is the result of the difference between the amount of iron taken up by the body and the amount lost [see Figure 3]. Because humans are unable to excrete excess iron, iron balance is physiologically regulated by the control of iron absorption. The two major factors that influence iron absorption are the level of body iron stores and the extent of erythropoiesis.16 If iron stores increase, absorption decreases; if stores decrease, absorption increases. Absorption also increases with increased erythropoietic activity, especially with ineffective erythropoiesis. Most of the iron in the body is located in the erythron, which consists of the totality of circulating erythrocytes and their precursors in the bone marrow. The predominant pathway of internal iron flux is a oneway flow from the plasma iron transport protein, transferrin, to the erythron, and then through the monocyte-macrophage system back to transferrin [see Figure 3]. The erythron uses about 80% of the iron passing through the transferrin compartment each day. Normally, the majority of this iron is used for hemoglobin synthesis and returned to the circulation within red blood cells. Small quantities of iron are stored in ferritin, enter the iron-containing enzymes of immature erythroid cells, or are lost in the products of ineffective erythropoiesis. At the end of their life span, senescent red cells are phagocytized by specialized macro-phages in the spleen, bone marrow, and liver, which then return most of the iron to the transferrin compartment, where the cycle begins again. The phagocytosis of flawed and aged erythrocytes accounts for almost all of the storage iron normally found in the macrophages of the liver, bone marrow, and spleen. By contrast, the parenchymal cells of the liver may either take iron from, or give iron to, plasma transferrin. Under normal physiologic conditions, iron recycling is very efficient; less than 0.05% of the total body iron is acquired or lost each day.
Blood is an amazing and vitally important part of the body,because it contains many finely-tuned chemical systems that allowit to maintain the chemical environment needed for the body'smetabolism. One of the most important functions of blood isdelivering O2 to all parts of the body by thehemoglobin protein. O2 is carried in the hemoglobinprotein by the heme group. The heme group (a component of thehemoglobin protein) is a metal complex, with iron as the centralmetal atom, that can bind or release molecular oxygen. Both thehemoglobin protein and the heme group undergo conformationalchanges upon oxygenation and deoxygenation. When one heme groupbecomes oxygenated, the shape of hemoglobin changes in such a wayas to make it easier for the other three heme groups in theprotein to become oxygenated, as well. This feature helps theprotein to pick up oxygen more efficiently as the blood travelsthrough the lungs. Hemoglobin also enables the body to eliminateCO2, which is generated as a waste product, via gasexchange in the blood (CO2 exchanged for O2in the lungs, and O2 exchanged for CO2 inthe muscles). The species generated as waste by theoxygen-consuming cells actually help to promote the release of O2from hemoglobin when it is most needed by the cells. Hence,hemoglobin is a beautiful example of the finely tuned chemicalsystems that enable the blood to distribute necessary moleculesto cells throughout the body, and remove waste products fromthose cells.
the two mechanisms that explain howHDL offers protection against chronic heart disease are that HDL inhibitscellular uptake of LDL and serves as a carrier that removes cholesterol fromthe peripheral tissues and transports it back to the liver for catabolism andexcretion