Continuous increase of alcohol dehydrogenase activity along the liver plate in normal and cirrhotic human livers

Abstract

To determine the zonal distribution of alcohol dehydrogenase in normal and cirrhotic human livers, we measured activities of this enzyme by quantitative cytochemical analysis along the liver cell plate in liver specimens from 10 normal organ donors and from 7 children with extrahepatic biliary atresia cirrhosis. In normal human liver samples, a continuous increase in alcohol dehydrogenase activity was observed along the sinusoid from the periportal to the perivenular hepatocytes (mean extinction units from 16.2 +/- 10.0 to 58.0 +/- 14.8). A similar observation was made in cirrhotic nodules, with activity increasing continuously from nodule periphery to center (7.6 +/- 4.1 to 44.9 +/- 13.3). This study demonstrates a heterogeneous pattern of alcohol dehydrogenase distribution along the sinusoid in normal human liver specimens. In addition, demonstration of this heterogeneity in human cirrhosis suggests that the cirrhotic liver is able to maintain a parenchymal functional organization, with persistence of metabolic zonation.

The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

“…Moreover, in all cirrhotic nodules examined, GLS was undetectable. This concurs with the lack of centri-DISCUSSION lobular veins in cirrhotic nodules and confirms the close topographical relation between the centrilobular microenvironOur study, confirming and extending previous results on selected enzymatic activities, [26][27][28][29][30][31][32][33][34][35][36] ammonia-metabolizing en-ment and the expression of GLS. The only marker retaining a heterogeneous distribution in cirrhosis was G6P activity, zymes, [37][38][39][40] and members of the cytochrome P450 multigene family, [15][16][17][41][42][43][44][45] shows that the human hepatic lobule presents which usually predominated at the periphery of cirrhotic nodules.…”

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

“…Recently, using single cell mRNA sequencing and spatial reconstruction, a global signature of zonation in mouse liver has been established 5 . Immunohistochemical analyses have confirmed the zonal distribution of metabolic enzymes, such as cytochrome P450 13 , 14 , alcohol dehydrogenase 15 , fatty acid-binding protein 16 , glucose-6-phosphatase and glutamine synthetase 17 in human liver. Relevant questions, such as the link of metabolic zonation to underlying morphogens, a global assessment of zonation and the underlying regulatory mechanisms and not least also the relation of rodent findings to human liver 18 are as yet not fully addressed 19 .…”

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

“…Recently, using single cell mRNA sequencing and spatial reconstruction, a global signature of zonation in mouse liver has been established 5 . Immunohistochemical analyses have confirmed the zonal distribution of metabolic enzymes, such as cytochrome P450 13,14 , alcohol dehydrogenase 15 , fatty acid-binding protein 16 , glucose-6phosphatase and glutamine synthetase 17 in human liver. Relevant questions, such as the link of metabolic zonation to underlying morphogens, a global assessment of zonation and the underlying regulatory mechanisms and not least also the relation of rodent findings to human liver 18 are as yet not fully addressed 19 .…”