Erythrocyte turnover

Plasma Haptoglobin in Relation to Hemoglobinemia, Hemoglobinuria and Erythrocyte Turnover... 

When human red cells were killed by storage in saline and reinjected intravenously, no increased consumption of Hp was observed (G9). Neither did the plasma Hp level change when the normal erythrocyte turnover was accelerated by injection of nicotinic acid (G10). Patients have also been observed who rapidly eliminated all red cells infused without consequent hemoglobinemia or decrease in the plasma Hp. 

Osaki, 1974 Osaki, 1966 Osaki et al., 1966). Using the kinetic values given above, they estimated that without the ferroxidase activity of Cp in the plasma 80% of the iron released from erythrocyte turnover would accumulate as non-Tf-bound Fe(ll) and thereby would be unavailable for reabsorption by the reticuloendothelial system. Furthermore, this free Fe(II) could catalyze the formation of reactive oxygen species via the Fenton reaction. This, in turn, could lead to a subsequent organismal pathophysiology (Miyajima et al., 1996 Nakano, 1993). This inference has been strikingly confirmed by research over the past 6 years in both yeasts and mammals this research has directly tested the hypothesis that multicopper oxidase-dependent ferroxidase activity is essential to eukaryotic iron homeostasis (Askwith et al., 1996 Harris et al., 1995 1998 Wessling-Resnick, 1999). 

The degradation of 1 g of hemoglobin yields 30 mg of bilirubin. A normal individual destroys 7.5 g of hemoglobin per day when 1 % of his circulating erythrocytes are replaced. At that rate of erythrocyte turnover, the daily bilirubin production equals 250 mg. The maximum capacity of the reticuloendothelial system to convert hemoglobin to bilirubin is five times that amount. 

Elevation of erythrocyte ZPP lags any increases in PbB due to increased exposure. ZPP levels, furthermore, remain elevated when exposure has ceased. The former arises from ZPP insertion into cells occurring only during active intoxication of bone marrow, whereas ZPP decay, when exposure ceases, is governed to some degree by the rate of erythrocyte turnover. 

Deficiency. Macrocytic anemia, megaloblastic anemia, and neurological symptoms characterize vitamin B 2 deficiency. Alterations in hematopoiesis occur because of the high requirement for vitamin B 2 for normal DNA repHcation necessary to sustain the rapid turnover of the erythrocytes. Abnormal DNA repHcation secondary to vitamin B 2 deficiency produces a defect in the nuclear maturational process of committed hematopoietic stem cells. As a result, the erythrocytes are either morphologically abnormal or die during development. 

It is apparent from the studies of Gydell et al. (N8), and of Brus and Lewis (B12) that anhaptoglobinemia is common in subjects with twice the normal turnover rate of the erythrocyte cell mass. 

Garby and Noyes (G4) have measured the kinetics of the disappearance of labeled, small amounts, of Hp-bound Hb in plasma. If their data are pooled with the normal mean values presented by Hank et al. (HI) for plasma Hb (0.3mg/100ml plasma), it will be evident that about 0.5 g Hb enters and leaves plasma per day, i.e., a little less than 10% of the normal Hb catabolized is released into, or returned to, the circulation. These data—if correct—can also be used to calculate the approximate amount of Hp engaged in our normal erythrocyte (Hb) turnover. We must assume that the dominating Hp complex formed when Hb enters the circulation in minute amounts is one molecule Hp and y2 molecule Hb, since the saturation of Hp is very low. We accept that the molecular weight of Hp is 100,000. About 1.4 g of Hp will then be con-... 

From the comparison by Nyman et al. between plasma Hp level and different red cell destruction indices (half-life of CrB1-tagged erythrocytes, endogenous CO formation, stercobilin (urobilin) excretion in feces) it is evident that anhaptoglobinemia is a very common, but not an invariable accompaniment of increased red cell turnover. The exceptions are possibly persons with increased Hp synthesis. Individual differences in efficiency to destroy red cells outside the circulation without Hb return may be reflected by the wide normal variation range of plasma Hp as well by the promptness with which anhaptoglobinemia develops on even slight increase in Hb turnover. 

Hp calculated by Nyman as 5 days may represent the half-life as a result of the normal catabolism—type (a)—if we ignore the erythrocyte destruction. It is meaningless to speak of half-life values of Hp when discussing Hp turnover absolute amount per unit of time and weight should, instead, be used. 

Acetylcholinesterase is subject to substrate Inhibition at high concentrations, but Mlchaells kinetics are observed at lower concentrations, because the substrate constant and the Mlchaells constant differ by a factor of 100. Turnover numbers run about 2-9 x 10 min l, and (Mlchaells constant) values are about 0.2 mM.76,116 Whatever the source, the enzyme is subject to inhibition by the same reversible and irreversible inhibitors. Most of the kinetic work has been done with the saline-extracted 11S enzyme from electric eel and the detergent-extracted 6S enzyme from erythrocytes. The former Is a tetramer derived from the native enzyme by the action of proteases the latter is a dimer. 

While it is assumed that hematopoietic cell formation is regulated through a concerted and coordinated release of factors in a cascade and series of reactions, the details of how such processes occur remain elusive. It is clear, however, that there are important differences in the growth and turnover (or removal) rates of blood cells. A new population of neutrophils is generated every 24 hours to replace aging cells, which are cleared with a half-life of about 6 to 8 hours [7]. On the other hand, erythrocytes exhibit a well-documented life... 

The existence of some blood cells, such as erythrocytes and platelets, with long lifespans make cell transfusion therapy practical. Cell transfusion therapy cannot be developed for short-lived cells such as neutrophils with turnover rates of less than 8 hours. Fortunately, for neutrophils, colony stimulating factors can be used to recruit the needed number in blood within 24 hours after administration of these factors. 

Additional information <1-7, 11, 14, 15, 17-19, 21, 30> (<7> cell-free synthesis in mRNA-dependent rabbit reticulocyte lysate system [40] <2,4,5> high activities in tissues where turnover of energy from adenine nucleotides is great, e. g. muscle [3] <1-6,11,14,15> tissue distribution [3,46] <2,5> rabbit and human carry a minimum of 2 sets of isozymes within an individual one set in muscle, erythrocytes, brain and another in liver, kidney and spleen [3]) [3, 40, 46]... 

Carbonic anhydrase of erythrocytes (Mr 30,000) has one of the highest turnover numbers we know of. It catalyzes the reversible hydration of C02 ... 

A number of studies have measured the activation of plasma transaminases by pyridoxal phosphate added in vitro however, it is difficult to interpret the results, because plasma transaminases arise largely accidentally, as a result of cell turnover, and the amount released will depend on tissue damage. Furthermore, there is a considerable amount of pyridoxal phosphate in plasma, largely associated with serum albumin, and the extent to which plasma transaminases are saturated will depend largely on the relative affinity of albumin and the enzyme concerned for the coenzyme, rather than reflecting the availability of pyridoxal phosphate for intracellular metabolism. Studies on erythrocyte transaminase activation coefficient are easier to interpret, because the extent to which the enzymes are saturated depends mainly on the availability of pyridoxal phosphate. 

Acetylcholinesterase (AChE) (also termed true cholinesterase ) is found in the synaptic cleft of cholinergic synapses, and is of undoubted importance in regulation of neurotransmission by rapid hydrolysis of released endogenous acetylcholine (ACh). AChE is also found in erythrocytes and in the CSF, and can be present in soluble form in cholinergic nerve terminals, but its function at these sites is not clear, AChE is specific for substrates that include acetylcholine and the agents methacholine and acetylthiocholine. but it has little activity with other esters. It has a maximum turnover rate at very low concentrations of AChE (and is inhibited by high concentrations). 

Hepatocellutar Disease. Most forms of acute or chronic hepatocellular disease, including acute viral hepatitis and cirrhosis with jaundice, are associated with decreased levels of Hp, possibly caused in part by altered estrogen metabolism. Increased red cell breakdown secondary to erythrocyte membrane lipid alterations may also play a role, although this has never been documented with turnover studies. In contrast, biliary obstruction is also associated with significant lipid alterations but with increased Hp levels, in the absence of severe hepatocellular disease. 

Staufenbiel, M. (1988). Fatty acids covalently bound to erythrocyte proteins undergo a differential turnover in vivo. J Biol Chem, 263 13,615-13,622. 

Using the serial data for the cerebral cortex, plasma, and erythrocytes, we constructed accumulation and decay curves for several key fatty acids in these tissues, which provided gross estimates of their turnover times after fish-oil feeding to n-3 fatty acid-deficient monkeys (Table 2). For cerebral cortex, a steady state was reached after 12 wk of fish-oil feeding for DHA, but 22 5n-6 took longer to decline to the low levels found in the cortex of control animals. The half-lives of DHA in cerebral phospholipids ranged from 17 to 21 d 21 d for phosphatidylethanolamine, 21 d for phosphatidylserine, 18 d for phosphatidylinositol, and 17 d for phosphatidylcholine. The corresponding values for 22 5n-6 in these same phospholipids were 32,49,14, and 28 d, respectively. The half-lives of linoleic acid, EPA, and DHA in plasma phospholipids were estimated to be 8,18, and 29 d, respectively. In the phospholipids of erythrocytes, linoleic acid, arachidonic acids, EPA, and DHA had half-lives of 28, 32, 14, and 21 d, respectively. 

Connor WE, Neuringer MA, Lin DS. Dietary effects on brain fatty acid composition the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res 1990 31 237-247. 

Proteasome research began in the late 1960s [19] when Harris discovered a barrel-shaped particle in erythrocyte extracts. From then on knowledge about the proteasome and the regulating factors of this protease has been added to step by step. Today it is generally accepted that the ubiquitin-proteasome system is responsible for the turnover of the bulk of intracellular cytosolic and nuclear proteins [20]. It is known that this protease is located in the cytosol, the nucleus, and that it is attached to the ER and other cell membranes. 

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