The activity of the metabolic form of hepatic phosphatidate phosphohydrolase correlates with the severity of alcoholic fatty liver in human beings

C P Day, O F James, A S Brown, M K Bennett, I N Fleming, S J Yeaman

Research output: Contribution to journalArticle

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Abstract

Increased esterification of fatty acids to triglyceride is common to most of the mechanisms proposed to explain the causation of alcoholic fatty liver. However, it is unclear whether this is caused by increased substrate supply or whether direct stimulation of the enzymes of the esterification pathway occurs after excessive alcohol intake. The rate-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatidate phosphohydrolase, which is present in the cytosol and microsomes and is sensitive to inhibition by N-ethylmaleimide. This enzyme is physically distinct from a second form of phosphatidate phosphohydrolase that is located predominantly in the plasma membrane, is insensitive to N-ethylmaleimide inhibition and has a putative role in cell-signaling. We have investigated whether the activity of the N-ethylmaleimide-sensitive ("metabolic") form of phosphatidate phosphohydrolase is increased in patients with alcoholic liver disease and whether any increased activity correlates with the severity of steatosis. N-ethylmaleimide-sensitive and -insensitive phosphatidate phosphohydrolase activities were measured in needle liver biopsy specimens from 42 alcoholic patients and 6 patients with primary biliary cirrhosis and in wedge biopsy specimens from 6 normal patients undergoing routine cholecystectomy. Steatosis was "scored" on coded slides from 0 to 3. N-ethylmaleimide-sensitive activity was higher in alcoholic biopsy specimens scoring 3 (3.25 +/- 0.4 units/mg protein, n = 10) than in those scoring either 0 (1.21 +/- 0.2, n = 14) or 1 to 2 (1.58 +/- 0.2, n = 18), and it was also higher than in biopsy specimens from normal and primary biliary cirrhosis patients (1.65 +/- 0.3, n = 12; p <0.0001, analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)
Original languageEnglish
Pages (from-to)832-8
Number of pages7
JournalHepatology
Volume18
Issue number4
Publication statusPublished - 1993

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Phosphatidate Phosphatase
Alcoholic Fatty Liver
Ethylmaleimide
Liver
Biliary Liver Cirrhosis
Esterification
Biopsy
Triglycerides
Enzymes
Alcoholic Liver Diseases
Cholecystectomy
Needle Biopsy
Alcoholics
Microsomes
Causality
Cytosol
Analysis of Variance
Fatty Acids
Alcohols
Cell Membrane

Keywords

  • Adult
  • Aged
  • Biopsy, Needle
  • Cell Membrane
  • Cytosol
  • Ethylmaleimide
  • Fatty Liver, Alcoholic
  • Female
  • Humans
  • Liver
  • Male
  • Microsomes, Liver
  • Middle Aged
  • Phosphatidate Phosphatase

Cite this

The activity of the metabolic form of hepatic phosphatidate phosphohydrolase correlates with the severity of alcoholic fatty liver in human beings. / Day, C P; James, O F; Brown, A S; Bennett, M K; Fleming, I N; Yeaman, S J.

In: Hepatology, Vol. 18, No. 4, 1993, p. 832-8.

Research output: Contribution to journalArticle

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T1 - The activity of the metabolic form of hepatic phosphatidate phosphohydrolase correlates with the severity of alcoholic fatty liver in human beings

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AU - James, O F

AU - Brown, A S

AU - Bennett, M K

AU - Fleming, I N

AU - Yeaman, S J

PY - 1993

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N2 - Increased esterification of fatty acids to triglyceride is common to most of the mechanisms proposed to explain the causation of alcoholic fatty liver. However, it is unclear whether this is caused by increased substrate supply or whether direct stimulation of the enzymes of the esterification pathway occurs after excessive alcohol intake. The rate-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatidate phosphohydrolase, which is present in the cytosol and microsomes and is sensitive to inhibition by N-ethylmaleimide. This enzyme is physically distinct from a second form of phosphatidate phosphohydrolase that is located predominantly in the plasma membrane, is insensitive to N-ethylmaleimide inhibition and has a putative role in cell-signaling. We have investigated whether the activity of the N-ethylmaleimide-sensitive ("metabolic") form of phosphatidate phosphohydrolase is increased in patients with alcoholic liver disease and whether any increased activity correlates with the severity of steatosis. N-ethylmaleimide-sensitive and -insensitive phosphatidate phosphohydrolase activities were measured in needle liver biopsy specimens from 42 alcoholic patients and 6 patients with primary biliary cirrhosis and in wedge biopsy specimens from 6 normal patients undergoing routine cholecystectomy. Steatosis was "scored" on coded slides from 0 to 3. N-ethylmaleimide-sensitive activity was higher in alcoholic biopsy specimens scoring 3 (3.25 +/- 0.4 units/mg protein, n = 10) than in those scoring either 0 (1.21 +/- 0.2, n = 14) or 1 to 2 (1.58 +/- 0.2, n = 18), and it was also higher than in biopsy specimens from normal and primary biliary cirrhosis patients (1.65 +/- 0.3, n = 12; p <0.0001, analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

AB - Increased esterification of fatty acids to triglyceride is common to most of the mechanisms proposed to explain the causation of alcoholic fatty liver. However, it is unclear whether this is caused by increased substrate supply or whether direct stimulation of the enzymes of the esterification pathway occurs after excessive alcohol intake. The rate-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatidate phosphohydrolase, which is present in the cytosol and microsomes and is sensitive to inhibition by N-ethylmaleimide. This enzyme is physically distinct from a second form of phosphatidate phosphohydrolase that is located predominantly in the plasma membrane, is insensitive to N-ethylmaleimide inhibition and has a putative role in cell-signaling. We have investigated whether the activity of the N-ethylmaleimide-sensitive ("metabolic") form of phosphatidate phosphohydrolase is increased in patients with alcoholic liver disease and whether any increased activity correlates with the severity of steatosis. N-ethylmaleimide-sensitive and -insensitive phosphatidate phosphohydrolase activities were measured in needle liver biopsy specimens from 42 alcoholic patients and 6 patients with primary biliary cirrhosis and in wedge biopsy specimens from 6 normal patients undergoing routine cholecystectomy. Steatosis was "scored" on coded slides from 0 to 3. N-ethylmaleimide-sensitive activity was higher in alcoholic biopsy specimens scoring 3 (3.25 +/- 0.4 units/mg protein, n = 10) than in those scoring either 0 (1.21 +/- 0.2, n = 14) or 1 to 2 (1.58 +/- 0.2, n = 18), and it was also higher than in biopsy specimens from normal and primary biliary cirrhosis patients (1.65 +/- 0.3, n = 12; p <0.0001, analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

KW - Adult

KW - Aged

KW - Biopsy, Needle

KW - Cell Membrane

KW - Cytosol

KW - Ethylmaleimide

KW - Fatty Liver, Alcoholic

KW - Female

KW - Humans

KW - Liver

KW - Male

KW - Microsomes, Liver

KW - Middle Aged

KW - Phosphatidate Phosphatase

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JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -