Liver parenchymal cells

Figure 15-7. Intracellular location and overview of major metabolic pathways in a liver parenchymal cell. (AA —metabolism of one or more essential amino acids AA <->, metabolism of one or more nonessential amino acids.)...

Reynolds, E.S. (1967). Liver parenchymal cell injury IV Pattern of incorporation of carbon and chlorine atoms from carbon tetrachloride into chemical constituents of liver in vivo. J. Pharmacol. Exp. Therap. 155, 117-126. 

Researchers focused on the metabolically competent human hepatoma cell line HepG2 as a model of human liver. HepG2 cells are a well-known hepatoma cell line that retains many of the morphological characteristics of liver parenchymal cells. This model is often used as a useful tool for HRA/ERA-oriented chemical risk assessment due to the expression of antioxidant and xenobiotic metabolizing enzymes (in particular phase I and phase II enzymes responsible for the bioactivation/detoxification of various xenobiotics) that can be induced or inhibited by dietary and non-dietary agents [28-30]. 

Although many animal models for iron overload exist, some mimicking certain aspects of HH, the 32-microglobulin knockout mouse is of special interest as it revealed for the first time crucial aspects of the pathogenesis of human HH in an animal model, and also because it underlines the important links between iron metabolism and the immune system. Hepatic iron overload in 32-microglobulin ( 32m)-deficient mice appeared to be similar to that found in HH, with pathological iron depositions occurring predominantly in liver parenchymal cells (de Sousa et ah,... 

Bellemann, P. (1980). Primary monolayer culture of liver parenchymal cells and kidney cortical tubules as a useful new model for biochemical pharmacology and experimental toxicology. Studies in vitro on hepatic membrane transport, induction of liver enzymes, and adaptive changes in renal cortical enzymes. Arch. Toxicol. 44 63-84. 

Reynolds ES, Yee AG. 1967. Liver parenchymal cell injury. V. Relationships between patterns of chloromethane-C14 incorporation into constituents of liver in vivo and cellular injury. Lab Invest 16 591-603. 

Sell DA, Reynolds ES Liver parenchymal cell injury. VUE. Lesions of membranous cellular components following iodoform. 7 Cell Biol M-. 736-752, 1969... 

Reynolds ES, Yee AG. 1968. Liver parenchymal cell injury. Part VI. Significance of early glucose-6-phosphatase suppression and transient calcium influx following poisoning. Lab Invest 19 273- 281. 

Borenfreund, E., Higgins, P.J., Steinglass, M., and Beindich, A. (1975). Properties and malignant transformation of established rat liver parenchymal cells in cultme, J. NatL Cancer Inst. 55,375. 

The first two reactions in the cholesterol synthetic pathway are siri lar to those in the pathway that produces ketone bodies (see Figure 16.22, p. 194). They result in the production of 3-hydroxy-3-methyl-glutaryl CoA (HMG CoA, Figure 18.3). First, two acetyl CtA molecules condense to form acetoacetyl CoA. Next, a third molecule of acetyl CoA is added, producing HMG CoA, a six-carbon compound. [Note Liver parenchymal cells contain two isoenzymes of HMG CoA synthase. The cytosolic enzyme participates in cholesterol synthesis, whereas the mitochondrial enzyme Urc tions in the pathway for ketone body synthesis.]... 

Bile salts secreted into the intestine are efficiently reabsorbed (greater than 95 percent) and reused. The mixture of primary and secondary bile acids and bile salts is absorbed primarily in the ileum. They are actively transported from the intestinal mucosal cells into the portal blood, and are efficiently removed by the liver parenchymal cells. [Note Bile acids are hydrophobic and require a carrier in the portal blood. Albumin carries them in a noncovalent complex, just as it transports fatty acids in blood (see p. 179).] The liver converts both primary and secondary bile acids into bile salts by conjugation with glycine or taurine, and secretes them into the bile. The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are converted to bile acids, and their subsequent return to the liver as a mixture of bile acids and salts is termed the enterohepatic circulation (see Figure 18.11). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only about 0.5 g is lost daily in the feces. Approximately 0.5 g per day is synthesized from cholesterol in the liver to replace the lost bile acids. Bile acid sequestrants, such as cholestyramine,2 bind bile acids in the gut, prevent their reabsorption, and so promote their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note Dietary fiber also binds bile acids and increases their excretion.]... 

It has been reported that vitamin Kj and several of the vitamin K2 homologues are capable of restoring electron transport in solvent-extracted or irradiated bacterial and mitochondrial preparations. Other reports suggest that vitamin K is concerned with the phosphorylation reactions accompanying oxidative phosphorylation The capacity of these compounds to exist m several forms, e.g., quinone, quinol. chromanol, etc., appears to strengthen the proposal that links them to oxidative phosphorylation. Information has suggested that vitamin K acts to induce prothrombin synthesis. Since prothrombin has been shown to be synthesized only by liver parenchymal cells m the dog, it would appear that the proposed role for vitamin K is not specific for only prothrombin synthesis, but applicable to other proteins. 

Berry MN, Friend DS. High-yield preparation of isolated rat liver parenchymal cells a biochemical and fine structural study. J Cell Biol 1969 43 506-520. 

Savage, C. R., and Green, P. D., Biosynthesis of transcobalamin II by adult rat liver parenchymal cells in culture. Arch. Biochem. Biophys. 173, 691-702 (1976). 

There is abundant evidence that glucagon elevates cAMP levels in isolated liver parenchymal cells, in perfused liver and in the liver in vivo [58,59], As illustrated in Fig. 2, this occurs rapidly and with concentrations of the hormone [59] within the range found in portal venous blood in vivo i.e., 0.2-2 x 10-10 M. When sufficiently sensitive and accurate methods are employed to measure cAMP, an increase in the nucleotide is consistently observed in situations where the hormone induces metabolic responses [58,59]. However, an increase of only 2- to 3-fold is capable of inducing full stimulation of some major hepatic responses, e.g., phos-phorylase activation (Fig. 2) and gluconeogenesis [58,59]. Since higher concentrations of the hormone can elevate cAMP 10-fold or more [59] it appears that there is considerable receptor reserve for these responses. 

Blakey, D.C., Skilleter, D.N., Price, R.J., Watson, G.J., Hart, L.I., Newell, D.R., Thorpe, P.E. (1988). Comparison of the pharmacokinetics and hepatotoxic effects of saporin and ricin A-chain immunotoxins on murine liver parenchymal cells. Cancer Res. 48 7072-8. 

Loud, A.V. A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J. Cell Biol. 1968 37 27—46... 

Hepatic lipase is involved in the metabolism of high-density lipoproteins and intermediate density lipoproteins (IDLs), converting the HDL2 fraction to HDL3 and generating LDLs from IDLs. The enzyme appears to have broad specificity it hydrolyzes tri-, di-, and mono-acylglycerols, acyl-CoA thioesters, and even phospholipids. hHL is secreted by the liver parenchymal cells and does not require any cofactors for its activity. 

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