Blood cholinesterases forms

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

A variety of hydrolases catalyze the hydrolysis of acetylsalicylic acid. In humans, high activities have been seen with membrane-bound and cytosolic carboxylesterases (EC 3.1.1.1), plasma cholinesterase (EC 3.1.1.8), and red blood cell arylesterases (EC 3.1.1.2), whereas nonenzymatic hydrolysis appears to contribute to a small percentage of the total salicylic acid formed [76a] [82], A solution of serum albumin also displayed weak hydrolytic activity toward the drug, but, under the conditions of the study, binding to serum albumin decreased chemical hydrolysis at 37° and pH 7.4 from tm 12 1 h when unbound to 27 3 h for the fully bound drug [83], In contrast, binding to serum albumin increased by >50% the rate of carboxylesterase-catalyzed hydrolysis, as seen in buffers containing the hydrolase with or without albumin. It has been postulated that either bound acetylsalicylic acid is more susceptible to enzyme hydrolysis, or the protein directly activates the enzyme. 

In human blood, only 6-acetylmorphine was formed from heroin, with no 3-acetylmorphine or morphine being detected. Four kinetically distinct enzyme activities were seen, namely one in plasma, one in the cytosol of red blood cells, and two in red blood cell membranes [92], In human plasma at 37°, hydrolysis to 6-acetylmorphine occurs with a tm value of some minutes, the enzyme responsible being cholinesterase [90] [93]. These and other results tend to indicate that the formation of morphine from 6-acetylmorphine is due to tissue carboxylesterases, in particular cerebral enzymes [94],... 

Scarsella, G., G. Toschi, S. R. Bareggi, and E. Giacobini. 1979. Molecular forms of cholinesterase in cerebrospinal fluid, blood plasma and brain tissue of the beagle dog. Journal of Neuroscience Research 4 19-24. 

Carboxypeptidase A (approx. 35 kDa MW, Sigma Chemical) functions both as a peptidase and an esterase it is in this latter mode that it can serve as a detector for cholinesterase inhibitors. Unlike the other enzymes such as AChE or BChE, it does not have a serine residue in the active site. TPPSi forms a complex with the enzyme and, upon challenge with the cholinesterase inhibitor eserine (physostigmine) in water, exhibits a change in the absorbance spectrum with a new peak and a marked increase in absorbance at 423 nm. This suggests TPPS, may not be completely displaced from the active site. For actual sensor operations, the use of an enzyme such as BChE or carboxypeptidase in place of (or in addition to) AChE will allow for potential identification of the analyte based on different specificities/sensitivities of the enzyme. Enzymes such as OPH, which are not readily available, may be difficult to obtain in large quantities the supply of AChE is often limited perhaps due to the capture of electric eels, while proteins such as BChE (from horse blood) and carboxypeptidase (pancreas) are more readily available from slaughterhouses. 

Only a few enzymes are specifically secreted by organs into the blood stream. These are the enzymes of blood coagulation, cholinesterase, and amylase [21]. Serum, in the main, is a passive receptacle for enzymes derived from the tissue cells and the formed elements of blood. Normally, the level of enzymes in serum is both low and constant. Since most of the enzymes present are derived from cells, it follows that these enzymes must be able to pass through the limiting membrane of the parent cell. This outward passage is accomplished either by diffusion through pores or alternatively by the aid of an active transport system. Except in those cases where enzyme secretion is a physiological process, active transport is unlikely. The loss of enzymes from cells is accelerated by tissue injury, and also by metabolic inhibitors like 2,4-dinitrophenol, iodoacetate, and carbon monoxide [22]. The implication that the retention by the cell of a... 

Mercury in elemental form can evidently enter the blood circulation directly from inhaled vapor and absorption leads to increased urinary excretion which can be related to the airborne mercury level. A number of biological changes have been detected as a result of occupational exposure to mercury vapor in air [67]. These include increased plasma galactosidase and catalase activities and decrease in red blood corpuscle cholinesterase activity. 

After 4h, the higher proportion of radioactivity in all the tissues was in the form of bound [ H]DIP. Bound [ H]DIP levels did not follow a biphasic clearance curve and declined at a slower rate than [ H]DFP and free [ H]D1P tissue levels. By 5min, the greatest accumulation of boxmd [ H]DIP occurred in the liver (nearly 20% of the total body burden), with a noticeably small amount in the brain (0.1%). Total cholinesterase activity in the brain and red blood cells was inhibited by approximately 90%, with plasma pseudo cholinesterase activity and true cholinesterase activity inhibited by 99% and 97%, respectively. 

---