Red blood cells metabolism

N. Jamshidi, S. J. Wiback, and B. 0. Palsson, In silico model driven assessment of the effects of single nucleotide polymorphisms (SNPs) on human red blood cell metabolism. Gen. Res. 12 (11), 1687 1692 (2002). 

Y. Nakayama, A. Kinoshita, and M. Tomita, Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor. Biol. Med. Model. 2(1), 18... 

Jamshidi, N., J. S. I idwards, T. Fahland, G. M. Church, and B. O. Palsson. 2001. Dynamic simulation of the human red blood cell metabolic network. Bioinformatics 17 286-7. 

Esmolol is iv adrninistered. Maximal P-adrenoceptor blockade occurs in 1 min. Its elimination half-life is about 9 min. EuU recovery from P-adrenoceptor blockade is within 30 min after stopping the infusion. The therapeutic plasma concentrations are 0.4—1.2 lg/mL. It is metabolized by hydrolysis in whole blood by red blood cell esterases resulting in the formation of a primary acid metabohte and free methanol. The metabohte is pharmacologically inactive. The resulting methanol levels are not toxic. Esmolol is 55% bound to plasma protein, the acid metabohte only 10%. Less than 2% of parent dmg and the acid metabohte are excreted by the kidneys. Plasma levels may be elevated and elimination half-hves prolonged in patients with renal disease (41). 

The drug is metabolized rapidly in the liver, kidney, intestinal mucosa, and even red blood cells. Therefore it has a plasma half-life of only 10 min after bolus intravenous application. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of the dose is excreted in the urine within 24 h, with less than 10% appearing as cytarabine the remainder is ara-U. After continuous infusion, cytarabine levels in the liquor (cerebro-spinal fluid) approach 40% of that in plasma. Continuous infusion schedules allow maximal efficiency, with uptake peaks of 5-7 pM. It can be administered intrathecally as an alternative to methotrexate. 

High levels of lead can affect heme metabohsm by combining with SH groups in enzymes such as fer-rochelatase and ALA dehydratase. This affects porphyrin metabolism. Elevated levels of protoporphyrin are found in red blood cells, and elevated levels of ALA and of coproporphyrin are found in urine. 

Transferrin (Tf) is a Pj-globulin with a molecular mass of approximately 76 kDa. it is a glycoprotein and is synthesized in the liver. About 20 polymorphic forms of transferrin have been found, it plays a central role in the body s metabolism of iron because it transports iron (2 mol of Fe + per mole of Tf) in the circulation to sites where iron is required, eg, from the gut to the bone marrow and other organs. Approximately 200 billion red blood cells (about 20 mL) are catabolized per day, releasing about 25 mg of iron into the body—most of which will be transported by transferrin. 

THE RED BLOOD CELL HAS A UNIQUE RELATIVELY SIMPLE METABOLISM... 

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. 

Iron is another vital nutrient in the development of functioning erythrocytes it is essential for the formation of hemoglobin. Lack of iron leads to a decrease in hemoglobin synthesis and ultimately red blood cells. Normal homeostasis of iron transport and metabolism is depicted in Fig. 63-2.7 Approximately 1 to 2 mg of iron is absorbed through the duodenum each day, and the same amount is lost via blood loss, desquamation of mucosal cells, or menstruation. 

Mature red blood cells do not have nuclei, mitochondria, or microsomes therefore red blood cell function is supported through the most primitive and universal pathway. Glucose, the main metabolic substrate of red blood cells, is metabolized via two major pathways the Embden-Meyerhof glycolytic pathway and the hex-ose monophosphate pathway (Fig. 1). Under normal circumstances, about 90% of the glucose entering the red blood cell is metabolized by the glycolytic pathway and 10% by the hexose monophosphate pathway. 

The most important product of the hexose monophosphate pathway is reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Another important function of this pathway is to provide ribose for nucleic acid synthesis. In the red blood cell, NADPH is a major reducing agent and serves as a cofactor in the reduction of oxidized glutathione, thereby protecting the cell against oxidative attack. In the syndromes associated with dysfunction of the hexose monophosphate pathway and glutathione metabolism and synthesis, oxidative denaturation of hemoglobin is the major contributor to the hemolytic process. 

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

The carbon dioxide produced during cellular metabolism diffuses out of the cells and into the plasma. It then continues to diffuse down its concentration gradient into the red blood cells. Within these cells, the enzyme carbonic anhydrase (CA) facilitates combination of carbon dioxide and water to form carbonic acid (H2C03). The carbonic acid then dissociates into hydrogen ion (H+) and bicarbonate ion (HC03). 

Cells that do not have mitochondria (such as red blood cells) must use glucose for energy since they have no TCA cycle or oxidative phosphorylation. Without a constant glucose supply, these cells would die. The brain relies heavily on glucose metabolism for energy however, the brain can adapt to use alternative energy sources if glucose is not available. 

Liver Minor protein stores helps muscle metabolize protein Muscle Major site of protein stores for metabolic needs Adipose No significant protein stores Red blood cells No significant protein stores Brain No significant protein stores... 

The primary function of the mammalian red blood cell is to maintain aerobic metabolism while the iron atom of the heme molecule is in the ferrous (Fe+2) oxidation state however, copper is necessary for this process to occur (USEPA 1980). Excess copper within the cell oxidizes the ferrous iron to the ferric (Fe+3) state. This molecule, known as methemoglobin, is unable to bind oxygen or carbon dioxide and is not dissociable (Langlois and Calabrese 1992). Simultaneous exposure of sheep to mixtures of cupric acetate, sodium chlorite, and sodium nitrite produced a dose-dependent increase in methemoglobin formation (Calabrese et al. 1992 Langlois and Calabrese 1992). 

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