The Liver Cell

For the glucose producing cells in the liver and kidneys, there is a balance between the glucokinase and glucose-6-phosphatase GP, which can be called a push-push system. The net hepatic glucose output, Jhgo. can be described by  

The main function of the liver s glucose sensing activities is to provide a switch that directs GNG towards glycogen storage or towards glucose release. Only occasionally, Jgk becomes so large that there is a transient net glucose uptake [37, 38]. 

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Solberg and co-workers have applied discriminate analysis of clinical laboratory tests combined with careful clinical and anatomic diagnoses of liver disease in order to determine which combinations of the many dozen liver diagnostic tests available are the bes t ( ). These authors found that the measurement of GPT, GMT, GOT, ALP and ceruloplasmin were the most useful enzymatic tests, when combined with other non-enzymatic tests such as the measurement of bilirubin, cholesterol, hepatitis-B associated Australian antigen, etc. Another group of highly useful enzymes, not discussed in this review, are those clotting factors and the enzyme cholinesterase which are synthesized by the liver cells. 

Tocotrienols, gamma Oryzanol Phosphatidyl chohne Antioxidants Controls liver cirrhosis and helps in effective liver detoxification (Bruni, 1988). Protectant against hver damage (Kidd, 1996). Antioxidant enzymes prevent hpid peroxidation and helps protecting the liver cells from damage. 

Thomas Liver cells are carrying out a differentiated function and reside in GO. Upon damage or hepatectomy the liver cells re-enter the cycle. 

Biosynthesis of Unsaturated Fatty Acids. In the mammalian tissues, the forma-tion of monoene fatty acids is only possible. Oleic acid is derived from stearic acid, and palmitooleic acid, from palmitic acid. This synthesis is carried out in the endoplasmic reticulum of the liver cells via the monooxigenase oxidation chain. Any other unsaturated fatty acids are not produced in the human organism and must be supplied in vegetable food (plants are capable of generating polyene fatty acids). Polyene fatty acids are essential food factors for mammals. 

IX is accompanied by its transport back into the mitochondria whence it came, to undergo oxidation of its methylene groups to protoporphyrin IX and insertion of iron to yield the end product, haem. The two major sites of haem biosynthesis are erythroid cells, which synthesize around 85 % of the body s haem groups, and the liver, which synthesizes most of the remainder. A major function of haem in liver is as the prosthetic group of cytochrome P450, the importance of which in detoxification has been discussed in Chapter 2. The liver cell must synthesize cytochrome P450 throughout its lifetime in quantities that vary with conditions. In contrast, the... 

Lindahl-Kiessling, K., Karlberg, I. and Olofsson, A.M. (1989). Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen. Mutat. Res. 211 77-87. 

An anomaly associated with citrulline that became evident when detailed kinetic studies were made in the 1950s (R.B. Fisher and J.R. Bronk) was the irreproducibility of its catalytic activity in liver slices on the formation of urea, despite the clear evidence from Ratner and Petrack of its importance in arginine synthesis. Initially the discrepancy in catalytic activity between ornithine and citrulline was ascribed to the possible impermeability of the liver cell plasma membrane to the latter intermediate, a hypothesis which was rapidly disproved experimentally. Only recently has it been shown that ornithine transcarbamylase is clearly associated with the ornithine/... 

Glycogen synthase kinase-3 is itself subject to control by reversible phosphorylation. Stimulation of the liver cell by insulin, the key hormone of the postprandial state,... 

Unconjugated bilirubin is taken into the hepatocytes by binding to membrane transport proteins and transported through the liver cells to the SER by proteins called ligandins. The SER is the location of a specific bilirubin-UDP-glucuronosyl transferase... 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

The enzyme glucose 6-phosphatase, which catalyses the hydrolysis of glucose 6-phosphate to form glucose, is also present in the liver cell. 

Adrenaline increases the rate of gluconeogenesis it binds to the a-receptor on the surface of the liver cell, which results in an increase in cytosolic concentration of Ca " ions (Chapter 12). This increases the activity of the Ca " -catmodulin-dependent protein kinase which phosphory-lates and causes similar changes in the activities of the enzymes PFK-2 and pyruvate kinase to those resulting from activation of cyclic-AMP-dependent protein kinase. Hence Ca " ions increase the rate of gluconeogenesis. 

The physiological relevance together with chnical importance of transamination and deamination is wide-ranging. As an aid to understanding the somewhat complex nature of amino acid metabolism, it can be considered (or imagined) as a metabolic box (represented in Figure 8.13). Some pathways feed oxoacids into the box whereas others remove oxoacids and the ammonia that is released is removed to form urea. The box illustrates the role of transdeamination as central to a considerable amount of the overall metabolism in the liver cell (i.e. protein, carbohydrate and fat metabohsm, see below). 

This compartmentation of processes in the liver cells occurs with other pathways glycolysis occurs mainly in the perivenous cells whereas gluconeogenesis occurs mainly in the periportal cells (Chapter 6). 

Figure 22.10 Reverse cholesterol transfer. High density lipoprotein (HDL) collects cholesterol from cells in various tissues/ organs the complex is then transported in the blood to the liver where it binds to a receptor on the hepatocyte, is internalised and the cholesterolis released into the hepatocyte. This increases the concentration in the liver cells which then decreases the synthesis of cholesterol by inhibition of the rate-limiting enzyme in cholesterol synthesis, HMG-CoA synthase. The cholesterol is also secreted into the bile or converted to bile acids which are also secreted into the bile, some of which is lost in the faeces (Chapter A).

The hepatocarcinogenicity of dieldrin in mice has been confirmed in several experiments, and in some cases, the liver cell tumors metastasized. No excess of tumors has been observed in a number of bioassays in rats and one bioassay in Syrian golden hamsters. ... 

Alcohol has a range of effects for some, desirable acute effects unwanted effects on the developing fetus and with long-term consumption, effects on the liver and other organs. In the US, over 2 million people experience alcohol related liver disease. Effects on the liver are dose related the more you consume the greater the effects. Early on there is an accumulation of fat in the liver as a result of the metabolism of alcohol. Some heavy drinkers develop an inflammation (alcoholic hepatitis) of the liver. Metabolites of alcohol, produced by the liver, are toxic to the liver cells. 

Insufficient inorganic phosphate (especially in the liver cells of affected persons who ingest a large amount of fructose) impairs gluconeogenesis, protein synthesis, and energy production by oxidative phosphorylation. 

Put very simply two sorts of drug-metabolizing enzymatic processes occur in the microsomes of the smooth endoplasmic reticulum or in the cytosol of liver cells. The first, so-called Phase F, reactions may add or subtract a small portion of the drug molecule, commonly by oxidation. This by itself may make a product more water-soluble, but, more commonly, a second step - Phase IF- process is required in which the altered drug is coupled (conjugated - literally married ) to compounds already existing in the liver cells to form salts such as glu-curonides and sulphates (Fig. 3). 

Among the cardiac glycosides, digitoxin is absorbed rapidly and completely from the gastrointestinal tract with oral absorption of approximately 90 to 100 percent with plasma protein binding of approx. 95 percent with plasma half life of 5 to 7 days. It enters the liver cells where it is metabolised to epidigitoxigenin and is excreted in bile and urine. 

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