Serum enzymes origins

Measurement of serum y-GT activity has clinical significance. The enzyme is present in all tissues, but the highest level is in the kidney however, the serum enzyme originates primarily from the hepatobiliary system. Elevated levels of serum y-GT are found in the following disorders intra- and posthepatic biliary obstruction (elevated serum y-GT indicates cholestasis, as do leucine aminopeptidase, 5 -nucleotidase, and alkaline phosphatase) primary or disseminated neoplasms some pancreatic cancers, especially when associated with hepatobiliary obstruction alcohol-induced liver disease (serum y-GT may be exquisitely sensitive to alcohol-induced liver injury) and some prostatic carcinomas (serum from normal males has 50% higher activity than that of females). Increased activity is also found in patients receiving phenobarbital or phenytoin, possibly due to induction of y-GT in liver cells by these drugs. 

It has been determined that different tissues produce or express different CK isoenzymes. Skeletal muscle cells express the CK-MM isoenzyme almost exclusively, while brain cells and cells of the gastrointestinal tract express the CK-BB isoenzyme almost exclusively. Cardiac muscle cells, however, express an approximate 1 3 ratio of the CK-MB and CK-MM isoenzymes, respectively. If you had a means of determining which isoenzyme is present at elevated levels in the serum, you might be able to determine what type of tissue the enzyme originated from. 

The muscle damage associated with the trauma of surgery wfll increase the serum activity of enzymes originating in skeletal muscle, and this increased activity may persist for several days. Typical alterations in activity of serum enzymes following surgery are illustrated in Table 17-13. Increased tissue catabolism requires increased oxygen consumption and also leads to the production of acid metabofites. Thus blood lactate may increase twofold to threefold. With tissue anoxia and impairment of renal and respiratory function, a metabolic acidosis develops. With tissue destruction, there is increased urinary excretion of the major biochemical components of skeletal muscle. 

Tissues of Origin of Some Diagnostically Important Serum Enzymes... 

The association of hyperphosphatasemia with tumors of nonbone origins has been reported, as in the case of pancreatic cancer (S16), but the source of the serum enzyme has not been clearly traced back to the tumor. 

M16. Meade, B. W., and Rosalki, S. B., The origin of increased maternal serum enzyme activity in pregnancy and labour. J. Obstet. Gynecol. Brit. Commonwealth 70, 862-868 (1963). 

The use of LDH and CPK levels alone can also lead to a misdiagnosis because these enzymes are produced by many tissues. How can a cUnidan diagnose heart disease with confidence when the elevated serum enzyme levels could indicate coexisting disease in another tissue The physidan is able to make such a decision because of the presence of isoenzymes, which provide diagnostic accuracy because they reveal the tissue of origin. 

The amylase activities in whole and in fractionated haemolymphs of the molluscs Crassostrea virginica and Mercenaria mercenaria have been measured. Amylase occurs only in whole haemolymphs and in the sera of C. virginica, originating from the crystalline style. Possible roles for the serum enzyme were discussed. 

The Group II (biliary tract) enzymes are abnormal usually when the serum bilirubin concentration is also abnormal. Most commonly used is alkaline phosphatase which is a highly sensitive indicator of biliary tract obstruction, perhaps because the enzyme is synthesized as an induced response to obstruction of even small bile ducts. Most techniques used to identify the origin of an elevated serum alkaline phosphatase are not very useful from a clinical viewpoint (23). The simultaneous measurement of GMT activity has been found to be useful in differentiating between the hepatic and bony origin of alkaline phosphatase. An increased GMT activity in a patient with an increased ALP activity is a good indication that there is biliary biliary tract disease (62,63). 

Although rum ammonia levels are not routinely measured, it is a useful indicator of Reye s syndrome and should be monitored in newborns at risk of developing hyperammonemia Ammonia is produced in many analytically useful enzyme reactions and the ammonium ISE has been used as the base sensor in several enzyme electrodes (see next section). In addition to valinomycin, other antibiotics such as the nonactin homalogs and gramicidins also behave as ionophores. The nonactin homolo were originally studied for their ability to selectively bind potassiiun ions It was then discovered that ammonium ions were preferred over potassium ions, and the selectivity coefficient Knh+ = 0.12 was reported. Since ammonia is present at fairly low levels in serum, this selectivity is not sufficient to to accurately measure NH4 in the presence of K. An extra measure of selectivity can be gained by using a gas permeable membrane to separate the ammonia gas from the sample matrix... 

Probably the most effective use of XRF and TXRF continues to be in the analysis of samples of biological origin. For instance, TXRF has been used without a significant amount of sample preparation to determine the metal cofactors in enzyme complexes [86]. The protein content in a number of enzymes has been deduced through a TXRF of the sulfur content of the component methionine and cysteine [87]. It was found that for enzymes with low molecular weights and minor amounts of buffer components that a reliable determination of sulfur was possible. In other works, TXRF was used to determine trace elements in serum and homogenized brain samples [88], selenium and other trace elements in serum and urine [89], lead in whole human blood [90], and the Zn/Cu ratio in serum as a means to aid cancer diagnosis [91]. 

Among potentiometric enzyme sensors, the urea enzyme electrode is the oldest (and the most important). The original version consisted of an enzyme layer immobilized in a polyacrylamide hydrophilic gel and fixed in a nylon netting attached to a Beckman 39137 glass electrode, sensitive to the alkali metal and NHj ions [19, 2A Because of the poor selectivity of this glass electrode, later versions contained a nonactin electrode [20,22] (cf. p. 187) and especially an ammonia gas probe [25] (cf. p. 72). This type of urea electrode is suitable for the determination of urea in blood and serum, at concentrations from 5 to 0.05 mM. Figure 8.2 shows the dependence of the electrode response... 

Serum ALP and total bilirubin (unconjugated and conjugated fractions) are traditionally used to monitor cholestatic injury. The ALP families of enzymes are zinc metalloproteases that are present in nearly all tissues. In the liver, ALP is immu-nolocalized to the microvili of the bile canaliculus [124]. Increased synthesis of ALP and its release into the circulation occurs within hours of cholestatic injury [129]. Serum assays of 5 -nucleotidase (5 -NT) or y-glutamyltransferase activity (GGT) are used to confirm the liver as the specific origin for the elevation of ALP. Increases in serum bilirubin or bile acids are usually the result of bile retention subsequent to impaired bile flow, increased production associated with accelerated erythrocyte destruction, or altered bilirubin metabolism [129]. 

If you have a class with biochemists, clearly the area of enzyme kinetics is practically mandatory. If biologists are mixed in with the biochemists, osmotic pressure is an important concept to cover carefully and a concept typically not well covered in general chemistry and in most physical chemistry texts or classes. A quick example what is a 2 Osmolar solution of sodium chloride Such concentration units are used when dispensing various saline solutions in hospitals. What is the origin of the unit A 1 M NaCl solution dissociates into two ions that would double the osmotic pressure of a non dissociating solute. Thus, the 1 M solution of NaCl becomes a 2 Osmolar solution. Other examples abound - the bursting pressure of a cell relates to the osmotic pressure of the serum in which the cell finds itself. 

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