A J Levi

Bio: A J Levi is an academic researcher from Albert Einstein College of Medicine. The author has contributed to research in topics: Bilirubin & Jaundice. The author has an hindex of 6, co-authored 6 publications receiving 939 citations. Previous affiliations of A J Levi include Mount Desert Island Biological Laboratory.

Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions

Abstract: Two hepatic cytoplasmic protein fractions, designated Y and Z, which bind sulfobromophthalein (BSP), bilirubin, and other organic anions, have been separated by G75 Sephadex gel filtration. The physiologic role of these protein fractions has been investigated. They are present in the 110,000 g supernatant fraction from the livers of all the species tested (rats, mice, guinea pigs, Rhesus monkeys, sheep, and man). Tissues which do not preferentially extract BSP or bilirubin from plasma do not contain these fractions, with the exception of small intestinal mucosa which contains Z. Anion binding by Y and Z fractions is not due to contamination with albumin. These fractions are responsible for the cytoplasmic localization of bilirubin in Gunn rats, and the fractions bind bilirubin, BSP, or indocyanine green (ICG), whether given in vivo or added in vitro to liver supernate from normal rats. Flavaspidic acid-N-methylglucaminate, bunamiodyl, and iodipamide, drugs known to interfere with the hepatic uptake mechanism, compete with bilirubin and BSP for binding to Z. These proteins appear to be important in the transfer of organic anions from plasma into the liver and provide a tool for the investigation of hepatic uptake mechanisms.

Studies of Y and Z, two hepatic cytoplasmic organic anion-binding proteins: effect of drugs, chemicals, hormones, and cholestasis

Abstract: The process by which various anions, including bilirubin and several dyes, drugs, hormones and their metabolites, are transferred from plasma into the liver cell is poorly understood. Two hepatic cytoplasmic proteins, Y and Z, that bind various organic anions in vivo and in vitro have been postulated to be involved in this process. The concentration of Y, the major organic anion-binding protein, increases in rat liver after administration of phenobarbital in association with enhanced organic anion transfer from plasma into liver as determined by initial plasma disappearance rate (K(1)) and hepatic dye content for sulfobromophthalein (BSP) and indocyanine green (ICG), as well as increased relative hepatic storage of BSP. Acute bile duct ligation failed to alter plasma disappearance or hepatic content of BSP in normal or phenobarbital-treated rats. Other drugs and chemicals which cause proliferation of hepatic smooth endoplasmic reticulum and enhancement of drug metabolism, such as allylisopropylacetamide, dieldrin, DDT, 3-methylcholanthrene, and benzpyrene increased Y and BSP K(1) and, where studied, hepatic BSP content. Alcohol feeding had no effect on Y, Z, or K(1) for BSP. Hypophysectomy and thyroidectomy increased Y but decreased K(1) and, where studied, hepatic content of BSP. Of several hormones studied, only thyroxine restored Y and K(1) to normal in hypophysectomized or thyroidectomized rats. Mice with congenital pituitary insufficiency also manifested increased Y which returned to normal after thyroxine administration. In hormone-deficient rats and mice, phenobarbital administration produced a further increase in Y suggesting that different mechanisms may be responsible for the change in Y resulting from drug administration and hormonal deprivation. Thyroxine, testosterone, or hydrocortisone did not alter BSP K(1) or Y in normal rats.Cholestasis produced by ethinyl estradiol administration or biliary obstruction reduced Y, Z, BSP K(1) and hepatic BSP content. These results support the hypothesis that Y and Z are involved in the transfer of BSP, ICG, and possibly other organic anions from plasma into the liver. The concentration of Y increased after administration of various drugs and chemicals as well as in thyroid deficiency. Thyroid hormone appears to be important in regulation of the intracellular concentration of Y. Because thyroid deficiency increased Y but decreased BSP K(1) and hepatic BSP content, other factors beside Y and Z influence hepatic organic anion uptake.

Deficiency of Hepatic Organic Anion-Binding Protein, Impaired Organic Anion Uptake by Liver and Physiologic Jaundice in Newborn Monkeys

Abstract: The possibility that "physiologic" jaundice in monkeys results from immaturity of the hepatic organic anion-uptake process was investigated by serial measurement of the initial plasma clearance of intravenously administered bromsulfalein (BSP), the serum bilirubin concentration and the hepatic intracellular concentration of Y and Z, two cytoplasmic organic anion-binding proteins. The intracellular concentration of Y, plasma clearance of BSP and serum bilirubin concentrations were abnormal in newborn monkeys and reached mature values within the first 10 days of life. These findings suggest that relative deficiency of Y, the main acceptor protein, may be important in the etiology of "physiologic jaundice" in monkeys as well as other primates, including man.

Phylogenetic Study of Organic Anion Transfer from Plasma into the Liver

Abstract: THE discovery of two intracellular proteins, Y and Z, with the unique property of binding certain organic anions, may help to account for the selective and rapid transfer of bilirubin and various dyes, drugs, steroids and metabolites from plasma into the liver, which is known to occur among mammals1–3. In the rat, from which they were first isolated3, Y and Z have been shown to possess the following characteristics, (i) They selectively bind organic anions, such as bilirubin, sulphobromophthalein (BSP) and indocyanine green, in vivo and in vitro3, (ii) The principal organic anion binding protein, Y, is present predominantly in the liver3,4, (iii) The concentration of Y increases after administration of phenobarbital, DDT and other drugs and concomitantly the rate of organic anion transfer into the liver is increased5. Furthermore, in the newborn monkey, the concentration of Y and the transfer into the liver of BSP, as measured by plasma disappearance rates, are both low and subsequently increase6. We report here the results of a phylogenetic study involving various vertebrates. These results further support the theory that Y and Z are intracellular acceptors which facilitate the transfer of certain organic anions from plasma into the liver.

The Glutathione Status of Cells

Abstract: Publisher Summary Glutathione (GSH) is the most important nonprotein thiol in living systems and is of widespread occurrence in the intracellular milieu of animals, plants, and microorganisms GSH was isolated and named by the English biochemist Frederick Gowland Hopkins This chapter discusses GSH status, the biologically relevant chemistry of GSH, the forms in which GSH can be present within the cell, along with the GSH content of cells and the methods for analysis of this substance GSH-related biochemical reactions and the biological roles of GSH are discussed in the chapter The use of perturbations in GSH status as a means for investigating GSH-related phenomena and an analysis of the consequences of perturbation are presented A short summary of genetic lesions related to GSH is also included Like chemically induced perturbations in GSH status, genetic lesions provide valuable insights into the role of GSH in normal functions and processes in cells The chapter concludes with some brief comments about the future of the relationship of GSH status to cellular processes

The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents.

Abstract: Publisher Summary This chapter discusses the role of glutathione (GSH) and glutathione s-transferases in metabolism of chemical carcinogens and other electrophilic agents. GSH is a tripeptide (I) that is present in nearly all living cells and is the most abundant sulfhydryl compound present in animal tissues, mainly in the cytosol. The chapter illustrates the wide range of electrophilic agents, including several known mutagens and carcinogens, which conjugate with GSH, a process usually catalyzed by the GSH S-transferases. This conjugation is probably a protective mechanism and is the initial stage in mercapturic acid biosynthesis for the elimination of foreign compounds from the body. GSH S-transferases provide protection not only by catalyzing the conjugation of a potential toxicant with GSH, but also by preferentially binding, even covalently, that toxicant. The reactive electrophiles that conjugate with GSH also bind to DNA, RNA, and protein and identification of GSH conjugates provide information on the nature of these biologically active intermediates or even their immediate precursors. Thus, the knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.

Antioxidant activity of albumin-bound bilirubin.

Abstract: Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space.

A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium, and other tissues.

Abstract: A protein of molecular weight approximately 12,000 which binds long-chain fatty acids and certain other lipids has been identified in cytosol of intestinal mucosa, liver, myocardium, adipose tissue, and kidney. Binding is noncovalent and is greater for unsaturated than for saturated and medium-chain fatty acids. This protein appears to be identical with the smaller of two previously described cytoplasmic anion-binding proteins. Binding of long-chain fatty acids by this protein is greater than that of other anions tested, including sulfobromophthalein, and does not depend on negative charge alone. The presence of this binding protein may explain previously observed differences in intestinal absorption among fatty acids, and the protein may participate in the utilization of long-chain fatty acids by many mammalian tissues.