Effects of ethanol and fat on the transport of reducing equivalents into rat liver mitochondria

Cederbaum, AI; Lieber, CS; Toth, A; Beattie, DS; Rubin, E

HERO ID

2919662

Reference Type

Journal Article

Year

1973

Language

English

PMID

4352184

HERO ID 2919662
In Press No
Year 1973
Title Effects of ethanol and fat on the transport of reducing equivalents into rat liver mitochondria
Authors Cederbaum, AI; Lieber, CS; Toth, A; Beattie, DS; Rubin, E
Journal Journal of Biological Chemistry
Volume 248
Issue 14
Page Numbers 4977-4986
Abstract Chronic ethanol intoxication in rats accelerated the rate of ethanol metabolism, but decreased the activity of alcohol dehydrogenase. Chronic consumption of ethanol decreased the activities of cytochrome oxidase and succinic dehydrogenase in mitochondria and in cell-free homogenates, whereas total hepatic mitochondrial protein was not altered by ethanol feeding. Thus, total "mitochondrial activity" was decreased and cannot account for the increased rate of blood ethanol elearance. We therefore investigated the activities of mitochondrial enzymes and those of "shuttle" systems for the transport of reducing equivalents into mitochondria. Reconstituted malate-aspartate, fatty acid, and α-glycerophosphate shuttles were equally effective in transporting reducing equivalents into the mitochondria from ethanol-fed and control rats. The activities of enzymes involved in the shuttles, such as cytoplasmic and mitochondrial α-glycerophosphate dehydrogenase and glutamic oxalacetic transaminase, were either decreased or unchanged by chronic ethanol consumption. The permeability of the mitochondria to NADH and to substrate anions which participate in the shuttles was also not altered by ethanol feeding. It is therefore unlikely that the increased rates of ethanol oxidation produced by chronic ethanol consumption are caused by enhanced transport of reducing equivalents into the mitochondria. A high fat diet alone (35% of total calories) increased both the endogenous and total rates of shuttle activity, compared with the rates obtained with mitochondria from rats which had consumed a low fat diet. However, the rates of blood ethanol clearance were comparable in rats consuming high fat and low fat diets. Therefore, the transport of reducing equivalents into the mitochondria under these conditions does not appear to be rate-limiting for ethanol metabolism.
Pmid 4352184
Wosid WOS:A1973Q264200018
Url http://www.jbc.org/content/248/14/4977.abstract
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English