Effect of alcohol on albumin synthesis by the isolated perfused rat liver

Kirsch, Ralph E.; Frith, L.; Stead, Robin H.; Saunders, S. J.

doi:10.1093/ajcn/26.11.1191

Cited by 31 publications

(5 citation statements)

References 15 publications

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“…A systematic overestimation of urea specific radioactivity would also be difficult to explain on methodological grounds alone. Urea-synthetic rates are based on stable urea measurements at multiple time-points, and the results compare well with those published by Kirsch et al (1969Kirsch et al ( , 1973 and Kelman et al (1972). In contrast, radial immunodiffusion demonstrated linear continued synthesis of albumin throughout perfusion at rates similar to or slightly lower than those observed in vivo (Jeejeebhoy et al, 1972).…”

Section: Discussionsupporting

confidence: 74%

“…These workers' choice ofa 4h time-point for comparison ofthe specific radioactivities of [14C]urea and [6-14C]arginine in labelled albumin was arbitrary but was opportune in ensuring good agreement. Other workers (Kirsch et al, 1969(Kirsch et al, , 1973Kelman et al, 1972) have chosen to Vol. 150 administer the [14C]carbonate as a single pulse into the reservoir of the perfusion and to compare the specific radioactivities of ['4C]urea and [6-14C]arginine-labelled albumin 2-3h later.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver

Nadkarni

Metcalfe

Black

et al. 1975

Biochemical Journal

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A mathematical model was constructed to define the dynamics of incorporation of radioactivity into urea carbon and the guanidine carbon of arginine in plasma albumin after the rapid intraportal-venous administration of Na214CO3 in the isolated perfused rat liver. 2. The model was formulated in terms of compartmental analysis and additional experiments were designed to provide further information on subsystem dynamics and to discriminate between alternative model structures. 3. Evidence for the rapid-time-constant of labelling of intracellular arginine was provided by precursor-product analysis of precursor [14C]carboante and product [14C]urea in the perfusate. 4. Compartmental analysis of the dynamics of newly synthesized urea was based on the fate of exogenous [13C]urea, endogenous [14C]urea and the accumulation of [12C]urea in perfusate water, confirming the early completion of urea carbon labelling, the absence of continuing synthesis of labelled urea, and the presence of a small intrahepatic urea-delay pool. 5. Analysis of the perfusate dynamics of endogenously synthesized and exogenously administered [6-14C]arginine indicated that although the capacity for extrahepatic formation of [14C]-urea exists, little or no arginine formed within the intrahepatic urea cycle was transported out of the liver. However, the presence of a rapidly turning-over intrahepatic arginine pool was confirmed. 6. On the basis of these subsystem analyses it was possible to offer feasible estimations for the parameters of the mathematical model. However, it was not possible to stimulate the form and magnitude of the dynamics of newly synthesized labelled urea and albumin which were simultaneously observed after administration of [14C]carbonate on the basis of a preliminary model which postulated that both products were derived from a single hepatic pool of [16-14C]arginine. On the other hand these observed dynamics could be satisfied to a two-compartment arginine model, which also provided an explanation for discrepancies observed between albumin synthesis measured radioisotopically and immunologically. This was based on a relative overestimation of [14C]urea specific radioactivity resulting from the rapid dynamics of [14C]carbonate and the [14C]urea subsystem relative to the labelled albumin subsystem. The effects of arginine compartmentalization could be minimized in the model by minor slowing of the rate of [14C]carbonate turnover or by constant infusion of [14C]carbonate, both of which permitted valid determination of albumin-synthesis rates.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver

Nadkarni

Metcalfe

Black

et al. 1975

Biochemical Journal

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“…This seems unlikely as other blood proteins such as gamma‐2A immunoglobulin heavy chain were unaffected by feeding rats a diet containing ethanol, and CD166 antigen precursor is greatly increased. Supporting the idea that albumin may be specifically decreased by chronic alcohol ingestion, albumin synthesis by the isolated perfused rat liver was significantly reduced by acute alcohol exposure (Kirsch et al., 1973). Reductions in some of these plasma proteins, including albumin, can be a sign of hepatic dysfunction or protein malnutrition.…”

Section: Resultsmentioning

confidence: 87%

Impact of Chronic Alcohol Ingestion on Cardiac Muscle Protein Expression

Fogle¹,

Lynch²,

Palopoli³

et al. 2010

Alcoholism Clin & Exp Res

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Background Chronic alcohol abuse contributes not only to an increased risk of health-related complications, but also to a premature mortality in adults. Myocardial dysfunction, including the development of a syndrome referred to as alcoholic cardiomyopathy, appears to be a major contributing factor. One mechanism to account for the pathogenesis of alcoholic cardiomyopathy involves alterations in protein expression secondary to an inhibition of protein synthesis. However, the full extent to which myocardial proteins are affected by chronic alcohol consumption remains unresolved. Methods The purpose of this study was to examine the effect of chronic alcohol consumption on the expression of cardiac proteins. Male rats were maintained for 16 weeks on a 40% ethanol-containing diet in which alcohol was provided both in drinking water and agar blocks. Control animals were pair-fed to consume the same caloric intake. Heart homogenates from control- and ethanol-fed rats were labeled with the cleavable isotope coded affinity tags (ICAT™). Following the reaction with the ICAT™ reagent, we applied one-dimensional gel electrophoresis with in-gel trypsin digestion of proteins and subsequent MALDI-TOF-TOF mass spectrometric techniques for identification of peptides. Differences in the expression of cardiac proteins from control- and ethanol-fed rats were determined by mass spectrometry approaches. Results Initial proteomic analysis identified and quantified hundreds of cardiac proteins. Major decreases in the expression of specific myocardial proteins were observed. Proteins were grouped depending on their contribution to multiple activities of cardiac function and metabolism, including mitochondrial-, glycolytic-, myofibrillar-, membrane-associated, and plasma proteins. Another group contained identified proteins that could not be properly categorized under the aforementioned classification system. Conclusions Based on the changes in proteins, we speculate modulation of cardiac muscle protein expression represents a fundamental alteration induced by chronic alcohol consumption, consistent with changes in myocardial wall thickness measured under the same conditions.

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“…Acute ethanol administration to animals has been reported to inhibit hepatic synthesis of both constituent (46)(47)(48) and export (49)(50)(51)(52) proteins in vivo and in vitro. Other investigators iFERRIN have reported that chronic ethanol administration increases protein synthesis in ribosomes (46) and microsomes (53), whereas acute administration produces opposite effects.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of alcohol-induced accumulation of protein in the liver.

Baraona¹,

Leo²,

Borowsky³

et al. 1977

J. Clin. Invest.

298

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A B S T R A C T Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism ofthis protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.

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Effect of alcohol on albumin synthesis by the isolated perfused rat liver

Cited by 31 publications

References 15 publications

Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver

Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver

Impact of Chronic Alcohol Ingestion on Cardiac Muscle Protein Expression

Pathogenesis of alcohol-induced accumulation of protein in the liver.

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