Physiol Rev Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Physiol. Rev. 69: 708-764, 1989;
0031-9333/89 $15.00
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jungermann, K.
Right arrow Articles by Katz, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jungermann, K.
Right arrow Articles by Katz, N.

Physiological Reviews, Vol 69, 708-764, Copyright © 1989 by American Physiological Society

JOURNAL ARTICLE

Functional specialization of different hepatocyte populations

K. Jungermann and N. Katz
Institut fur Biochemie, Georg-August-Universitat, Gottingen, Federal Republic of Germany.

Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures and thus have different metabolic capacities. Therefore the model of metabolic zonation proposes a functional specialization for the two zones: 1) oxidative energy metabolism with beta-oxidation, amino acid catabolism, ureagenesis, gluconeogenesis for the synthesis of both glucose and glycogen, cholesterol synthesis, bile formation, and protective metabolism are predominantly located in the periportal zone; 2) glycolysis, glycogen synthesis from glucose, liponeogenesis, ketogenesis, glutamine formation, and xenobiotic metabolism are preferentially situated in the perivenous zone. The input of humoral and nervous signals into the two zones is different. During passage of blood through the liver acinus, concentration gradients of oxygen, substrates, and hormones are established; the nerve densities in the two zones seem to be different. The different expression of the genome in upstream and downstream hepatocytes can be caused among other factors by the zonal gradients in oxygen and hormone concentrations. The functional specialization of the different hepatocyte populations is especially well documented for carbohydrate, amino acid, ammonia, and xenobiotic metabolism as well as for bile formation by a number of different approaches. Zonal flux differences were calculated from enzyme and metabolite distributions measured in vivo. They were observed in periportal- and perivenous-like hepatocytes in cell culture and in hepatocyte populations enriched in periportal and perivenous cells. They were detected also during ortho-and retrograde liver perfusion and finally by noninvasive techniques, using surface micro-light guides and miniature oxygen electrodes. The peculiar zonal hepatotoxicity of many xenobiotics can be explained at least in part by the enzymatic and fine-structural hepatocellular heterogeneity.


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
A. Braeuning, R. Sanna, J. Huelsken, and M. Schwarz
Inducibility of Drug-Metabolizing Enzymes by Xenobiotics in Mice with Liver-Specific Knockout of Ctnnb1
Drug Metab. Dispos., May 1, 2009; 37(5): 1138 - 1145.
[Abstract] [Full Text] [PDF]

Home page
 Clin Med ResHome page
K. D. Sumida, J. M. Hill, and A. V. Matveyenko
Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption
Clin. Med. Res., October 1, 2007; 5(3): 193 - 202.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
A. Braeuning, C. Ittrich, C. Kohle, A. Buchmann, and M. Schwarz
Zonal Gene Expression in Mouse Liver Resembles Expression Patterns of Ha-ras and {beta}-Catenin Mutated Hepatomas
Drug Metab. Dispos., April 1, 2007; 35(4): 503 - 507.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. Zhong, P. Gastaminza, J. Chung, Z. Stamataki, M. Isogawa, G. Cheng, J. A. McKeating, and F. V. Chisari
Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus and Host
J. Virol., November 15, 2006; 80(22): 11082 - 11093.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Z. Khan, G. K. Michalopoulos, and D. B. Stolz
Peroxisomal Localization of Hypoxia-Inducible Factors and Hypoxia-Inducible Factor Regulatory Hydroxylases in Primary Rat Hepatocytes Exposed to Hypoxia-Reoxygenation
Am. J. Pathol., October 1, 2006; 169(4): 1251 - 1269.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
L. M. Aleksunes, G. L. Scheffer, A. B. Jakowski, I. M. Pruimboom-Brees, and J. E. Manautou
Coordinated Expression of Multidrug Resistance-Associated Proteins (Mrps) in Mouse Liver during Toxicant-Induced Injury
Toxicol. Sci., February 1, 2006; 89(2): 370 - 379.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
J. J. Loor, H. M. Dann, R. E. Everts, R. Oliveira, C. A. Green, N. A. J. Guretzky, S. L. Rodriguez-Zas, H. A. Lewin, and J. K. Drackley
Temporal gene expression profiling of liver from periparturient dairy cows reveals complex adaptive mechanisms in hepatic function
Physiol Genomics, October 17, 2005; 23(2): 217 - 226.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
P. Aspichueta, S. Perez, B. Ochoa, and O. Fresnedo
Endotoxin promotes preferential periportal upregulation of VLDL secretion in the rat liver
J. Lipid Res., May 1, 2005; 46(5): 1017 - 1026.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. Fandrey
Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R977 - R988.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
D. S. Edgerton, S. Cardin, D. Neal, B. Farmer, M. Lautz, C. Pan, and A. D. Cherrington
Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog
Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E510 - E522.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
S. Burkhardt, R. Bahnemann, K. Failing, and M. Reinacher
Zonal Distribution of Cell Proliferation in the Liver of Untreated B6C3F1 and C57BL Mice
Toxicol Pathol, January 1, 2004; 32(1): 100 - 105.
[Abstract] [PDF]

Home page
 DiabetesHome page
H. C. Murphy, G. Regan, I. G. Bogdarina, A. J.L. Clark, R. A. Iles, R. D. Cohen, G. A. Hitman, C. L. Berry, Z. Coade, C. J. Petry, et al.
Fetal Programming of Perivenous Glucose Uptake Reveals a Regulatory Mechanism Governing Hepatic Glucose Output During Refeeding
Diabetes, June 1, 2003; 52(6): 1326 - 1332.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Biol.Home page
P. J. Walsh, G. D. Mayer, M. Medina, M. L. Bernstein, J. F. Barimo, and T. P. Mommsen
A second glutamine synthetase gene with expression in the gills of the gulf toadfish (Opsanus beta)
J. Exp. Biol., May 1, 2003; 206(9): 1523 - 1533.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
S. M. Gustavson, C. A. Chu, M. Nishizawa, B. Farmer, D. Neal, Y. Yang, E. P. Donahue, P. Flakoll, and A. D. Cherrington
Interaction of glucagon and epinephrine in the control of hepatic glucose production in the conscious dog
Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E695 - E707.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Avogaro, G. Toffolo, E. Kiwanuka, S. V. de Kreutzenberg, P. Tessari, and C. Cobelli
L-Arginine-Nitric Oxide Kinetics in Normal and Type 2 Diabetic Subjects: A Stable-Labelled 15N Arginine Approach
Diabetes, March 1, 2003; 52(3): 795 - 802.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. S. Edgerton, S. Cardin, C. Pan, D. Neal, B. Farmer, M. Converse, and A. D. Cherrington.
Effects of Insulin Deficiency or Excess on Hepatic Gluconeogenic Flux During Glycogenolytic Inhibition in the Conscious Dog
Diabetes, November 1, 2002; 51(11): 3151 - 3162.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Gullberg, M. Rudling, C. Salto, D. Forrest, B. Angelin, and B. Vennstrom
Requirement for Thyroid Hormone Receptor {beta} in T3 Regulation of Cholesterol Metabolism in Mice
Mol. Endocrinol., August 1, 2002; 16(8): 1767 - 1777.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. Zandieh Doulabi, M. Platvoet-ter Schiphorst, H. C. van Beeren, W. T. Labruyere, W. H. Lamers, E. Fliers, O. Bakker, and W. M. Wiersinga
TR{beta}1 Protein Is Preferentially Expressed in the Pericentral Zone of Rat Liver and Exhibits Marked Diurnal Variation
Endocrinology, March 1, 2002; 143(3): 979 - 984.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
F. Desy, Y. Burelle, P. Belanger, M. Gascon-Barre, and J.-M. Lavoie
Effects of acute exercise on the gluconeogenic capacity of periportal and perivenous hepatocytes
J Appl Physiol, September 1, 2001; 91(3): 1099 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. R. Landau
Methods for measuring glycogen cycling
Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E413 - E419.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Krones, K. Jungermann, and T. Kietzmann
Cross-Talk between the Signals Hypoxia and Glucose at the Glucose Response Element of the L-Type Pyruvate Kinase Gene
Endocrinology, June 1, 2001; 142(6): 2707 - 2718.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
J. G. Bode, T. Peters–Regehr, R. Kubitz, and D. Häussinger
Expression of Glutamine Synthetase in Macrophages
J. Histochem. Cytochem., March 1, 2000; 48(3): 415 - 422.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
D. O'Sullivan, J. T. Brosnan, and M. E. Brosnan
Catabolism of arginine and ornithine in the perfused rat liver: effect of dietary protein and of glucagon
Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E516 - E521.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
T. Kietzmann, K. I. Hirsch-Ernst, G. F. Kahl, and K. Jungermann
Mimicry in Primary Rat Hepatocyte Cultures of the In Vivo Perivenous Induction by Phenobarbital of Cytochrome P-450 2B1 mRNA: Role of Epidermal Growth Factor and Perivenous Oxygen Tension
Mol. Pharmacol., July 1, 1999; 56(1): 46 - 53.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. D. Cortese
Rat liver GTP-binding proteins mediate changes in mitochondrial membrane potential and organelle fusion
Am J Physiol Cell Physiol, March 1, 1999; 276(3): C611 - C620.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. Imai, T. Mine, M. Tagami, K. Hanaoka, and T. Fujita
Zonal differences in effects of HGF/SF and EGF on DNA synthesis in hepatocytes under fed or starved conditions
Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1394 - G1401.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
V. M. Christoffels, T. Grange, K. H. Kaestner, T. J. Cole, G. J. Darlington, C. M. Croniger, and W. H. Lamers
Glucocorticoid Receptor, C/EBP, HNF3, and Protein Kinase A Coordinately Activate the Glucocorticoid Response Unit of the Carbamoylphosphate Synthetase I Gene
Mol. Cell. Biol., November 1, 1998; 18(11): 6305 - 6315.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. G. Jones, M. A. Solomon, A. D. Sherry, F. M. H. Jeffrey, and C. R. Malloy
13C NMR measurements of human gluconeogenic fluxes after ingestion of [U-13C]propionate, phenylacetate, and acetaminophen
Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E843 - E852.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. E. Halseth, N. Rheaume, A. B. Messina, E. K. Reed, M. G. Krishna, P. J. Flakoll, D. B. Lacy, and D. H. Wasserman
Regulation of hepatic glutamine metabolism during exercise in the dog
Am J Physiol Endocrinol Metab, October 1, 1998; 275(4): E655 - E664.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. A. Eugenin, H. Gonzalez, C. G. Saez, and J. C. Saez
Gap junctional communication coordinates vasopressin-induced glycogenolysis in rat hepatocytes
Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G1109 - G1116.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
W. J. C. Geerts, A. Jonker, L. Boon, A. J. Meijer, R. Charles, C. J. F. Van Noorden, and W. H. Lamers
In Situ Measurement of Glutamate Concentrations in the Periportal, Intermediate, and Pericentral Zones of Rat Liver
J. Histochem. Cytochem., September 1, 1997; 45(9): 1217 - 1230.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
G. L. Kedderis
Biochemical Basis of Hepatocellular Injury
Toxicol Pathol, January 1, 1996; 24(1): 77 - 83.
[Abstract] [PDF]

Home page
 DevelopmentHome page
R. Notenboom, P. de Boer, A. Moorman, and W. Lamers
The establishment of the hepatic architecture is a prerequisite for the development of a lobular pattern of gene expression
Development, January 1, 1996; 122(1): 321 - 332.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
H. Lie-Venema, W. T. Labruyère, M. A. van Roon, P. A. J. de Boer, A. F. M. Moorman, A. J. M. Berns, and W. H. Lamers
The Spatio-temporal Control of the Expression of Glutamine Synthetase in the Liver Is Mediated by Its 5`-Enhancer
J. Biol. Chem., November 24, 1995; 270(47): 28251 - 28256.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. H. Wenger, A. Rolfs, H. H. Marti, C. Bauer, and M. Gassmann
Hypoxia, a Novel Inducer of Acute Phase Gene Expression in a Human Hepatoma Cell Line
J. Biol. Chem., November 17, 1995; 270(46): 27865 - 27870.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Ekberg, V. Chandramouli, K. Kumaran, W. C. Schumann, J. Wahren, and B. R. Landau
Gluconeogenesis and Glucuronidation in Liver in Vivo and the Heterogeneity of Hepatocyte Function
J. Biol. Chem., September 15, 1995; 270(37): 21715 - 21717.
[Abstract] [Full Text] [PDF]

Home page
 JPEN J Parenter Enteral NutrHome page
B. P. Bode
Novel Control of the Position-Dependent Expression of Genes in Hepatocytes: The Glut-1 Transporter
JPEN J Parenter Enteral Nutr, January 1, 1994; 18(1): 83 - 84.
[Abstract] [PDF]

Home page
 JPEN J Parenter Enteral NutrHome page
B. R. Landau
Noninvasive Approaches to Tracing Pathways in Carbohydrate Metabolism
JPEN J Parenter Enteral Nutr, May 1, 1991; 15(3): 74S - 77S.
[Abstract] [PDF]

Home page
 JPEN J Parenter Enteral NutrHome page
D. Haussinger
Liver Glutamine Metabolism
JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 56S - 62S.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
V. M. Christoffels, P. E. M. H. Habets, A. T. Das, D. E. W. Clout, M. A. van Roon, A. F. M. Moorman, and W. H. Lamers
A Single Regulatory Module of the Carbamoylphosphate Synthetase I Gene Executes Its Hepatic Program of Expression
J. Biol. Chem., December 15, 2000; 275(51): 40020 - 40027.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online