CoChat
Sign Up
Cited by 607Liver physiology and pathologyDrug-Induced Hepatotoxicity and ProtectionOrgan Transplantation Techniques and Outcomes

The DOI matches its Crossref record; 854 of the 880 references it cites were found in a registry or an index.

Metabolic zonation of the liver: Regulation and implications for liver function

Gebhardt, Rolf·1992·Pharmacology & Therapeutics
DOI 10.1016/0163-7258(92)90055-5
Open this paper in CoChat — free account

Abstract

Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the various metabolic pathways and functions forms the basis for the efficient adaptation of liver metabolism to the different nutritional requirements of the whole organism in different metabolic states. The present review summarizes current knowledge about this heterogeneity, its development and determination, as well as about its significance for the understanding of all aspects of liver function and pathology, especially of intermediary metabolism, biotransformation of drugs and zonal toxicity of hepatotoxins.

Overview

Integrity signals

Registry

Crossref · 10.1016/0163-7258(92)90055-5

Cites

854 of 854 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 880 references

Research works printed but not linked: 39

  1. Almdal, 1987, Acute decrease in ureagenesis does not influence acid-base regulation, J. Hepatol. Suppl. 1, 4, 1
  2. Bjerrum, 1989, No effect of metabolic alkalosis on urea synthesis in man, Scand. J. Clin. Lab. Invest., 49, 613, 10.3109/00365518909091536 · DOI
  3. Burger, 1987, Heterogenität des Glutaminstoffwechsels in der Rattenleber, Dissertation Universität Tübingen
  4. Chamlian, 1987, Etude ultrastructurale de l'héterogeneité lobulaire du glycogéne hépatique chez l'homme, Cell. Mol. Biol., 33, 547
  5. De Groot, 1987, Reciprocal regulation of glutamine synthetase and carbamoyl phosphate synthetase in rat liver, Biochem. biophys. Acta, 908, 231
  6. Forkert, 1988, Distribution and induction sites of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P450 in murine liver: immunohistochemical localization antibodies, Molec. Pharmac., 34, 736
  7. Gardemann, 1987, Nervous control of glycogenolysis and hemodynamics in arterially and portally perfused rar liver, Am. J. Physiol., 253, E238
  8. Gebhardt, 1988, Veränderte Topographie der Glutamine Synthetase in Leberbiopsien zirrhotischer Patienten, Z. Gastroenterologie, 26, 22
  9. Geller, 1965, Intralobular distribution of polyploid cells in rat liver, Anat. Rec., 151, 352
  10. Guillouzo, 1982, New findings of immunolocalization of albumin in rat hepatocytes, Biol. Cell, 43, 163
  11. Gumucio, 1983, Functional and anatomical heterogeneity in the liver acinus. Impact on transport, Am. J. Physiol., 244, G578
  12. Gumucio, 1978, Bile secretion and liver heterogeneity, J. Lab. clin. Med., 91, 350
  13. Hardison, 1981, Nature of bile acid and maximum secretory rate in the rat, Am. J. Physiol., 241, G337
  14. Harisch, 1985, Studies on tissue distribution of glutathione-related enzymes after carbon tetrachloride-induced liver injury, Res. Commun. Chem. Path. Pharmac., 47, 399
  15. Hubbard, 1989, Localization of halothane metabolite antibodies, Clin. exp. Immunol., 76, 422
  16. Katz, 1975, Autoregulatory switch from glycolysis to gluconeogenesis in rat hepatocyte suspensions, Hoppe-Seyler's Z. Physiol. Chem., 356, 244
  17. Kitagawa, 1980, Reelevation of γ-glutamyltranspeptidase activity in periportal hepatocytes of rats with age, Gann, 71, 362
  18. Lamers, 1989, The metabolic lobulus, a key to the architecture of the liver, Vol. 19, 5
  19. Le Bouton, 1969, Relations and extent of the zone of intensified metabolism in the liver acinus, Curr. Modern Biol., 3, 4
  20. Lindros, 1987, Aldehyde dehydrogenase activities and NAD+-dependent formaldehyde oxidation in perivenous and periportal hepatocytes: effect of induction by β-naphtoflavone, Prog. clin. Biol. Res., 232, 77
  21. MacDonald, 1961, Liver cell regeneration due to biliary obstruction, Arch. Path., 72, 133
  22. MacDonald, 1960, Regeneration in fatty liver and cirrhosiss. Autoradiographic study using titrated thymidine, Arch. Path., 69, 175
  23. Matsumoto, 1982, The unit-concept of liver parenchyma. A reevaluation based on angioarchitectural studies, Acta Path., 32, 285
  24. Matsumura, 1986, Oxygen uptake in periportal and pericentral regions of the liver lobule in perfused liver, Am. J. Physiol., 250, G800
  25. Miller, 1981, Effect of albumin on the acinar distribution and biliary excretion of BSP in the rat, Hepatology, 1, 532
  26. Moorman, 1989, Development of hepatocyte heterogeneity, Vol. 19, 28
  27. Morgan, 1961, Juvenile Liver, Arch. Path., 71, 86
  28. Morrison, 1967, Quantitative measurements of alcohol dehydrogenase in the lobule of the liver, J. Lab. clin. Med., 70, 110
  29. Murakoshi, 1986, Ultrastructural and enzyme histochemical studies in orotic acid-induced fatty liver, Tokai J. exp. clin. Med., 11, 39
  30. Oberling, 1967, Les effects de l'intoxication aigue au tetrachlorure de carbone sur le foie de rat. Etude au microscope electronique, Ann. Anat. Path., 1, 401
  31. Runge, 1987, Cyclisches AMP: Synthese- und Abbaukapazität in mikrodisseziertem periporrtalem und perivenösem Lebergewebe der Ratte bei normaler Fütterung und Nahrungskarenz (Abstract), Z. Gastroenterol., 25, 54
  32. Schäfer, 1992, Selektive Proliferation perivenöser Hepatocyten nach Schädigung der Leber durch CCl4, Z. Gastroenterol., 30, 70
  33. Schrode, 1991, Induction of glutamine synthetase in periportal hepatocytes by a factor from liver epithelial cells (abstract), Eur. J. Cell Biol. Suppl. 32, 54, 74
  34. Schrode, 1992, Klonabhängige Unterschiede in der wechselseitigen Beeinflussung der Glutamin-Synthetase Aktivität in epithelialen Zellklonen und Hepatozyten, Z. Gastroenterol., 30, 94
  35. Seawright, 1972, The effect of prior dosing with phenobarbitone and diethylamino ethyl diphenylpropylacetate (SKF 525-A) on the toxicity and liver lesion caused by ngaione in the mouse, Br. J. exp. Path., 52, 242
  36. Speisky, 1985, Acinar distribution of γ-glutaryltransferase and glutathione in rat liver: Effect of acute ethanol administration, Hepatology, 5, 962
  37. Taira, 1980, Effects of phenobarbital, pregnenolone-16-α-carbonitrile and 3-methylcholanthrene pretreatments of the distributions of NADPH-cytochrome c (P450) reductase within the liver lobule, Molec. Pharmac., 18, 304
  38. Ugele, 1989, Transport und Metabolismus von gallengängigen Substanzen in isolierten und kultivierten Hepatocyten unter besonderer Berücksichtigung der Zonierung des Leberparenchyms, Dissertation Universität Tübingen
  39. Zavarzin, 1967, DNA synthesis and cell population kinetics in the ontogenesis of mammalia, Leningrad: Nauka, 141–155, 47

Cited by

Sorted by citations

Items 601–605 of 605

Related

See all

Metadata

Authors
Gebhardt, R.
Affiliations
University of Tübingen (DE)
Corresponding author
Gebhardt, Rolf
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
1992-01
Volume
53
Issue
3
Pages
275-354
ISSN
0163-7258 (ISSN-L)
DOI
10.1016/0163-7258(92)90055-5
OpenAlex
W2061717797
Cited by
607
References
880
Citations by year
2026: 17 · 2025: 23 · 2024: 16 · 2023: 30 · 2022: 22 · 2021: 31 · 2020: 33 · 2019: 30 · 2018: 29 · 2017: 19 · 2016: 18 · 2015: 15 · 2014: 19 · 2013: 21 · 2012: 15
FWCI
3.78
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
metabolic zonation, liver lobule, hepatocyte heterogeneity, intermediary metabolism, drug metabolism, hepatotoxins, liver function, liver pathology
MeSH terms
Animals, Humans, Liver

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review