Liver plasma enzyme activity

Liver contained 156 (68-563) pg PCB 126/kg FW pronounced liver enlargement lymphoid depletion of spleen 10-fold increase in hepatic microsomal EROD and benzyoxyresorufin-O-dealkylase 5-fold increase in methoxyresorufin-O-dealkylase Liver had 380 pg PCB 126/kg FW with increasing necrosis above effects plus decreased bone growth, decreased spleen weight, and degenerative lesions of thyroid Liver had 1.1 (0.6-4.5) mg PCB 126/kg FW above effects plus decreased body weight, decreased hepatic thiol concentrations, and increased plasma enzyme activities... 

Agarwal et al. 1978), the quantification of these specific enzymes may indicate that exposure to endosulfan has occurred. Blood tests, such as decay curves for aminopyrine in plasma, which are semiquantitative indices of liver enzyme induction, have been used successfully in the past to demonstrate enzyme induction in pesticide-exposed workers. Because numerous chemicals found at hazardous waste sites also induce these hepatic enzymes, these measurements are not specific for endosulfan exposure. However, measurements of enzyme activity, together with the detection of the parent compound or its metabolites in tissue or excreta, can be useful indicators of exposure. All of these potential biomarkers require further verification in epidemiological studies. Further studies with focus on the development of methods to separate and measure the estrogenicity of endosulfan in in vitro assays would be valuable since these assays are more sensitive and discriminative than other conventional biomarkers. Preliminary results have been presented by Sonnenschein et al. (1995). 

HDL is synthesized and secreted from both liver and intestine (Figure 25—5). However, apo C and apo E are synthesized in the liver and transferred from fiver HDL to intestinal HDL when the latter enters the plasma. A major function of HDL is to act as a repository for the apo C and apo E required in the metabohsm of chylomicrons and VLDL. Nascent HDL consists of discoid phosphohpid bilayers containing apo A and free cholesterol. These hpoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithimcholesterol acyltransferase (LCAT) and in the plasma of patients with obstructive jaundice. LCAT—and the LCAT activator apo A-I— bind to the disk, and the surface phosphohpid and free cholesterol are converted into cholesteryl esters and... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

Cows and calves fed low-zinc diets of 25 mg Zn/kg ration showed a decrease in plasma zinc from 1.02 mg/L at start to 0.66 mg/L at day 90 cows fed 65 mg Zn/kg diet had a significantly elevated (1.5 mg Zn/L) plasma zinc level and increased blood urea and plasma proteins (Ram-achandra and Prasad 1989). Biomarkers used to identify zinc deficiency in bovines include zinc concentrations in plasma, unsaturated zinc-binding capacity, ratio of copper to zinc in plasma, and zinc concentrations in other blood factors indirect biomarkers include enzyme activities, red cell uptake, and metallothionein content in plasma and liver (Binnerts 1989). 

A neutral activity has been described in liver plasma membranes (Slife et al, 1989) and in rat intestinal bmsh border membranes (Nilsson, 1969) little is known about this enzyme. Recently a 70 kDa neutral isoform has been purified and cloned from the culture medium of the bacterium Pseudomonas... 

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

Many diseases that cause tissue damage result in an increased release of intracellular enzymes into the plasma. The activities of many of these enzymes are routinely determined for diagnostic purposes in diseases of the heart, liver, skeletal muscle, and other tissues. The level of specific enzyme activity in the plasma frequently correlates with the extent of tissue damage. Thus, determining the degree of elevation of a particular enzyme activity in the plasma is often useful in evaluating the prognosis for the patient. 

Some enzymes show relatively high activity in only one or a few tissues. The presence of increased levels of these enzymes in plasma thus reflects damage to the corresponding tissue. For example, the enzyme alanine aminotransferase ALT, see p. 248) is abundant in the liver. The appearance of elevated levels of ALTin plasma signals possible damage to hepatic tissue. Increases in plasma levels of enzymes with a wide tissue distribution provide a less specific indication of the site of cellular injury. This lack of tissue specificity limits the diagnostic value of many plasma enzymes. 

Esterification of cholesterol When cholesterol is taken up by HDL, it is immediately esterified by the plasma enzyme phos-phatidylcholine cholesterol acyltransferase (PCAT, also known as LCAT, in which "L" stands for lecithin). This enzyme is synthesized by the liver. PCAT binds to nascent HDLs, and is activated by apo A-l. PCAT transfers the fatty acid from carbon 2 of phosphatidyl-... 

Clearance may also be viewed as the loss of drug from an organ of elimination such as the liver or kidney. This approach enables evaluation of the effects of a variety of physiological factors such as changes in blood flow, plasma protein binding, and enzyme activity. Therefore, total systemic clearance is determined by adding the clearance (CL) values for each elimination organ or tissue ... 

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