Enzymes in blood plasma

The study of enzymes has immense practical importance. In some diseases, especially inheritable genetic disorders, there may be a deficiency or even a total absence of one or more enzymes. For other disease conditions, excessive activity of an enzyme may be the cause. Measurements of the activities of enzymes in blood plasma, erythrocytes, or tissue samples are important in diagnosing certain illnesses. Many drugs exert their biological effects through interactions with enzymes. And enzymes are important practical tools,... 

The rate of enzyme-catalyzed reactions typically shows a marked dependence on pH (Figure 8-7). Many of the enzymes in blood plasma show maximum activity in vitro in the pH range from 7 to 8. However, activity has been observed at pH values as low as 1.5 (pepsin) and as high as 10.5 (ALP). The optimal pH for a given forward reaction may be different from the optimal pH found for the corresponding reverse reaction. The form of tlie pH-dependence curve is a result of a number of separate effects including the ionization of the substrate and the extent of dissociation of certain key amino acid side chains in the protein molecule, both at the active center and elsewhere in the molecule. Both pH and ionic environment will also have an effect on the three-dimensional conformation of the protein and... 

Gombotz, W. et ah. Immobilized enzymes in blood-plasma exchangers via radiation grafting, Radiat. Phys. Chem., 25, 549, 1985. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

A major contribution of the free-radical scavenging activity in blood plasma is attributable to the macro-molecular proteins (Wayner et al., 1985) of which albumin is a primary component and trapping agertt (Holt et al., 1984). Serum sulphydryl levels, primarily albumin-related, are decreased in subjects with rheumatoid complicated coalworkers pneumoconiosis, indicative of exacerbated inflammatory R.OM production (Thomas and Evans, 1975). Experimental asbestos inhalation in rats leads to an adaptive but evidendy insufficient response by an increase in endogenous antioxidant enzymes (Janssen etal., 1990). Protection of the vascular endothelium against iron-mediated ROM generation and injury is afforded by the iron sequestiant protein ferritin (Balia et al., 1992). 

ACE is a rather nonspecific peptidase that can cleave C-terminal dipeptides from various peptides (dipeptidyl carboxypeptidase). As kininase 11, it contributes to the inactivation of kinins, such as bradykinin. ACE is also present in blood plasma however, enzyme localized in the luminal side of vascular endothelium is primarily responsible for the formation of angiotensin 11. The lung is rich in ACE, but kidneys, heart, and other organs also contain the enzyme. 

This enzyme [EC 3.4.17.3] (also referred to as lysine carboxypeptidase, arginine carboxypeptidase, kininase I, or anaphylatoxin inactivator) is a zinc-dependent member of peptidase family M14. The enzyme hydrolyzes the peptide bond at the C-terminus provided that the C-terminal amino acid is either arginine or lysine. The enzyme inactivates bradykinin and anaphylatoxins in blood plasma. 

The stability of the oligopeptide side-chains in blood plasma and serum was determined [251]. Based on these results it was possible to control the degradability of HPMA copolymers by a particular enzyme as well as in the in vivo system [169, 252]. 

Most of the signs and symptoms resulting from diazinon poisoning are due to the inhibition of an enzyme called acetylcholinesterase in the nervous system. This enzyme is also found in your red blood cells and a similar enzyme (serum cholinesterase) is found in blood plasma. The most common test for exposure to many organophosphorus insecticides, including diazinon, is to determine the level of cholinesterase activity in the red blood cells or plasma. This test requires only a small amount of blood and is routinely available in your doctor s office. It takes time for this enzyme to completely recover to normal levels following exposure. Therefore, a valid test may be conducted a number of days following the suspected exposure. This test indicates only exposure to an insecticide of this type. It does not specifically show exposure to diazinon. 

FIGURE 23-22 The composition of blood. Whole blood can be separated into blood plasma and cells by centrifugation. About 10% of blood plasma is solutes, of which about 10% consists of inorganic salts, 20% small organic molecules, and 70% plasma proteins. The major dissolved components are listed. Blood contains many other substances, often in trace amounts. These include other metabolites, enzymes, hormones, vitamins, trace elements, and bile pigments. Measurements of the concentrations of components in blood plasma are important in the diagnosis and treatment of many diseases. 

Reasons for the presence of enzymes in the plasma Enzymes can normally be found in the plasma either because they were specifically secreted to fulfill a function in the blood, or because they were released by dead or damaged cells. Many diseases that cause tissue damage result in an increased release of intracellular enzymes into the plasma. The activities of many of these enzymes (for example, creatine kinase, lactate dehydrogenase, and alanine aminotransferase) are routinely determined for diagnostic purposes in diseases of the heart, liver, skeletal muscle, and other tissues. 

Quon et al. (1985) investigated the stability of esmolol in blood, plasma, red blood cells, and purified enzymes (human serum pseudocholinesterase, human and dog serum albumin, acetyl choline esterase, carbonic anhydrases A and B and human haemoglobin). Udata et al. (1999) studied the hydrolysis of propranolol ester prodrugs in purified acetylcholine esterase. 

MRI CAs meet a variety of biomolecules in physiological environments, and may interact with proteins, human serum albumin (HSA), enzymes, and receptors. The binding of CAs to HSA is widely studied because it is the most abundant protein in blood plasma. HSA has a molecular weight of 66 kDa, a concentration of approximately 0.64 mM, and with two major binding sites, which are subdomains of IIA and III A [63]. 

Biotin forms part of several enzyme systems and is necessary for normal growth and body function. Biotin functions as a cofactor for enzymes involved in carbon dioxide fixation and transfer. These reactions are important in the metaboHsm of carbohydrates, fats, and proteins, as well as promotion of the synthesis and formation of nicotinic acid, fatty acids, glycogen, and amino acids (5—7). Biotin is absorbed unchanged in the upper part of the small intestine and distributed to all tissues. Highest concentrations are found in the Hver and kidneys. Little information is available on the transport and storage of biotin in humans or animals. A biotin level in urine of approximately 160 nmol/24 h or 70 nmol/L, and a circulating level in blood, plasma, or serum of approximately 1500 pmol/L seems to indicate an adequate supply of biotin for humans. However, reported levels for biotin in the blood and urine vary widely and are not a reHable indicator of nutritional status. 

Enzyme activators are substances, often inorganic ions, that are required for certain enzymes to become active as catalysts. Activators can be determined by their effect on the rates of enzyme-catalyzed reactions. For example, it has been reported that magnesium at concentrations as low as 10 ppb can be determined in blood plasma based on activation by this ion of the enzyme isocitric dehydrogenase. 

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