Specific activity in plasma

Radioactivity. The specific activity in plasma, defined as 10 dpm of C-radioactivity/mg of unlabeled ascorbic acid, is plotted against dissection time in Figure 1. The time courses of C-radioactivity for various tissues are presented in Figures 2-4. 

Despite the large scattering of the ratios of the specific activity in plasma to the specific activity in several organs (values not given), it appears that even after attainment of the pseudo steady state (distribution equilibrium) those ratios are higher than unity. This suggests the specific activity in plasma to be higher than in tissues. 

The specific activity in plasma was found to be higher than that in tissues, therefore the total turnover derived from plasma is lower than the turnover derived from radioactivity in tissues. 

Relevant kinetic parameters (half-life, body pool, and mean transit time in organs) can be calculated. According to Equation 1 the specific activity in plasma shows a triphasic decay with half-lives of ti = 1.1 h, t2 == 22 h, and 3 == 61 h. The half-lives ti and 2 essentially describe the distribution of the compound into the system. The third half-life of 61 h (2.5 d) is valid for all tissues after attainment of the distribution equilibrium and represents the overall half-life of elimination from the body under the special conditions of the study (ascorbate status of the animals). 

In the second time period after administration it was not possible to describe the dependency of excreted radioactivity on time by relating it to the time course of specific activity in plasma or by relating it to the time course of radioactivity in organs. Therefore, a second intermediate compartment X2 must be introduced. The complicated excretion pattern was finally represented by an empirical model (Figure 8). 

The ratio of the specific activities in plasma and tissues were larger than unity even after attainment of the steady state this finding could be caused by tissue ascorbate not exchanging with the introduced, labeled... 

Native enzyme is inactivated initially without loss of antibody reactivity. The inactivation reaction is catalyzed by a membrane protein present in all liver membranes but at highest specific activity in plasma membranes and at lowest activity in lysosomal membranes. Inactivation is greatly accelerated in the presence of disulfides such as oxidized glutathione or cystine and retarded by thiols. Disulfides on the membrane protein are implicated because treatment of membranes with dithiothreitol in the presence of iodoacetamide destroys the capacity to inactivate phosphoenolpyruvate carboxykinase. This treatment would reduce and fix protein disulfides. Inactivation requires a membrane protein that shows some tissue specificity, since plasma membranes from reticulocytes or erythrocytes are not active, nor are liposomes prepared from the lipids of liver microsomes. 

ApoD is found in association with LCAT and with apoA-I in the HDL fraction. Albers et al. used a specific antibody to apoD to remove all apoD by immunoadsorption chromatography from plasma about 64% of LCAT activity and 11% of apoA-I were also removed from plasma (A14). Purified apoD has an apparent Mr of 32,500, and appears as three isoforms on isoelectric focusing (pi 5.20, 5.08, and 5.00) (A14). An HDL apolipoprotein, Mr 35,000, has been thought to be apoD, and to be a cholesteryl ester transfer protein (i.e., to transfer newly synthesized esterified cholesterol from HDL to LDL) (C8). Cholesteryl ester transfer activity in plasma was removed by polyclonal immunoglobulin to apoD (C8, F10). However, Morton and Zilversmit (M41) were able to separate apoD and lipid transfer protein (i.e., the cholesteryl ester transfer protein, or lipid transfer protein I) by chromatography, and they showed that the removal of apoD from plasma by precipitation with specific antisera did not remove any lipid transfer activity. Albers et al. (A14) also showed that immunoadsorption with antibody specific for apoD removed all the apoD from plasma without removing any cholesteryl ester transfer activity. 

Rapid entry of a FA from plasma into the brain FA-CoA pool allows increased neuronal demand for the FA to be easily met by the large reservoir of unesterified FA in plasma. One to two minutes after a step elevation in plasma [9,10- H]palmitate or labeled arachidonate, specific activity of the respective brain FA-CoA pool has reached a steady state (Grange et al., 1995 Washizaki et al., 1994). At this time, the ratio of FA-CoA specific activity to plasma FA specific activity (X. in Eq. 4) is 0.02-0.04, attesting to marked dilution of plasma-derived FA-CoA by FA released from brain phospholipids (Fig. 2). 

The standard battery of biochemical tests used to assess liver function usually includes the measurement of the activity in plasma of one of the aminotransferases [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT)]. Such measurements are performed to assess the integrity of the hepatocyte membrane. The measurement of AST provides poor organ specificity due to the ubiquitous nature of the enzyme and both ALT and AST are relatively poor at detecting damage that is occurring to the centrilobular hepatocytes. The inadequacy of the aminotransferases at detecting centrilobular liver damage may be... 

The esterification of cholesterol in animals has attracted considerable research because of the possible involvement of cholesterol and its ester in various disease states (cf. Glomset and Norum, 1973, and Sections 12.1, 12.3 and 12.6). Cholesterol esters are formed by the action of lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43) which is particularly active in plasma (cf. Sabine, 1977, for a review of cholesterol metabolism). The reaction involves transfer of a fatty acid from position 2 of lecithin (phosphatidylcholine) to the 3-hydroxyl group of cholesterol with the formation of monoacyl-phosphatidylcholine. Although LCAT esterifies plasma cholesterol solely at the interface of high-density lipoprotein and very-low-density lipoprotein, the cholesterol esters are transferred to other lipoproteins by a particular transport protein (CETP cholesteryl ester transfer protein). Cholesteryl esters, in contrast to free cholesterol, are taken up by cells mostly via specific receptor pathways (Brown et aL, 1981), are hydrolysed by lysosomal enzymes and eventually re-esterified and stored within cells. LCAT may also participate in the movement of cholesterol out of cells by esterifying excess cholesterol in the intravascular circulation (cf. Marcel, 1982). 

The alkaline phosphatase activity in plasma is usually reduced to values below the age-related normal range. Overall, there is a tendency to observe the lowest values in the more severely affected individuals, but individual cases may display activity just below the normal range. Heterozygotes may have reduced values. For that reason, the diagnosis should be confirmed by the demonstration of substrate accumulation ex vivo. As a consequence of reduced phosphatase activity, three compounds are present at increased concentrations pyridoxal-phosphate (PLP vitamin B6) in plasma, inorganic pyrophosphate (PPi) in plasma and urine, and phosphoethanolamine (PET) in urine. Increased PLP is a sensitive marker for hypophosphatasia (provided no oral supplement has been ingested) and is probably quite specific. Its elevation in plasma does not appear to have clinical consequences, as intracellular levels are not increased. PPi is equally sensitive but not routinely determined. Urinary PET is moderately sensitive (it may be normal in mild cases) but potentially nonspecific. 

As noted above, a large number of tissues possess the ability to incorporate inorganic phosphate into phospholipides. No such synthesis is observed, however, when phosphate-P is mixed with plasma. The question raised by these observations, i.e., the site of synthesis of plasma phospholipides, has been partially answered with the aid of phosphate-P . The specific activities of plasma phospholipides observed when labeled inorganic phosphate is introduced into normal and hepatectomized dogs are recorded in Table XV. These results are consistent with the view that the liver is the main site of phosphorylation for plasma phospholipides. 

Friedlander and colleagues (58) observed furthermore that the additional amounts of radiophosphatides formed under the influence of choline do not long remain in the liver. They pass into the plasma and increase the specific activity of plasma phosphatides. A single feeding of 300 mg. choline chloride per kg. of body weight increases markedly the phosphatide turnover in the plasma, as seen in Figure 8. While after 12 hours the effect of choline is most pronounced, after the lapse of 96 hours the specific activity of the plasma phosphatides shows almost the same value as found in the controls. 

The mechanism by which choline increases the specific activity of plasma phosphorus is not known. Since this occurs in the absence of a... 

Bimbaumer, L., and Pohl, S. L., 1973, Relation of glucagon-specific binding sites to glucagon-dependent stimulation of adenylyl cyclase activity in plasma membranes of rat liver, /. Biol. Chem. 248 2056. 

Only small amounts of free T are present in plasma. Most T is bound to the specific carrier, ie, thyroxine-binding protein. T, which is very loosely bound to protein, passes rapidly from blood to cells, and accounts for 30—40% of total thyroid hormone activity (121). Most of the T may be produced by conversion of T at the site of action of the hormone by the selenoenzyme deiodinase (114). That is, T may be a prehormone requiring conversion to T to exert its metaboHc effect (123). 

Dihydroxyvitamin (283) is the endogenous ligand for the vitamin receptor (VDR). It modulates genomic function in a tissue and developmentaHy specific manner and affects ceU proliferation, differentiation, and mineral homeostasis (74). Vitamin mobilizes calcium from the bone to maintain plasma Ca " levels. Vitamin and VDR are present in the CNS where they may play a role in regulating Ca " homeostasis. Vitamin D has potent immunomodulatory activity in vivo. 

Chemical Pathology. Also referred to as clinical chemistry, this monitoring procedure involves the measurement of the concentration of certain materials in the blood, or of certain enzyme activities in semm or plasma. A variety of methods exist that allow (to variable degrees of specificity) the definition of a particular organ or tissue injury, the nature of the injurious process, and the severity of the effect (76). 

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