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

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.

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.

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?

  • Hepatocytes in zone 3 are more active in glycolysis and lipogenesis, reflecting the depletion of oxygen and nutrients near the central vein.

    “For example, hepatocytes in zone 1 are more involved in gluconeogenesis and beta-oxidation, reflecting the relatively oxygen- and nutrient-rich environment near the portal vein and hepatic artery, whereas hepatocytes in zone 3 are more active in glycolysis and lipogenesis, reflecting the depletion of oxygen and nutrients near the central vein3,4,6.”

    From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]

  • Within the lobule, hepatocytes are classically organized into three zones, with zone 1 proximal to the portal vein and hepatic artery, zone 3 proximal to the central vein, and zone 2 in the intermediate region.

    “Within the lobule, hepatocytes are classically organized into three zones, with zone 1 proximal to the portal vein and hepatic artery, zone 3 proximal to the central vein, and zone 2 in the intermediate region3,4.”

    From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]

  • Hepatocytes in zone 1 are more involved in gluconeogenesis and beta-oxidation, reflecting the relatively oxygen- and nutrient-rich environment near the portal vein and hepatic artery.

    “For example, hepatocytes in zone 1 are more involved in gluconeogenesis and beta-oxidation, reflecting the relatively oxygen- and nutrient-rich environment near the portal vein and hepatic artery, whereas hepatocytes in zone 3 are more active in glycolysis and lipogenesis, reflecting the depletion of oxygen and nutrients near the central vein3,4,6.”

    From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]

Cites

Flagged first, then by citations

26 of the 880 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

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