Abstract
Nutritional disturbances of protein metabolism in the liver are reviewed in relation to feeding experimental animals the following diets: a) purified diets deficient in amino acids; b) amino acid mixtures or single amino acids; c) protein-free (amino acid-free) diets; or d) hypertonic or hypotonic solutions. The effects of tube-feeding the diets or dietary components for days, hours, or minutes on hepatic polyribosomes and protein synthesis are described. Force-feeding a purified diet free of single essential amino acids induces within days morphologic changes resembling those that occur in humans with kwashiorkor, a world-wide nutritional deficiency disease in children. In this kwashiorkor-like model, hepatic protein synthesis and polyribosomal aggregation are increased. Administration of a complete amino acid mixture or tryptophan alone, but no other single amino acid, produces a rapid stimulation (within minutes) of hepatic protein synthesis and polyribosomal aggregation in animals that had been fasted, fed, or treated with hepatotoxic agents. A single tube-feeding of a protein-free (amino acid-free) diet induces within hours an increase in hepatic protein synthesis in fasted animals. Administration of hypertonic solutions rapidly (within minutes) inhibits, while administration of hypotonic solutions rapidly increases, hepatic protein systhesis. These experimental findings are reviewed in terms of how alterations in regulatory controls of hepatic protein synthesis may be influenced by nutritional disturbances. Such information may be of importance in designing and utilizing nutritional approaches in the therapy of liver diseases.
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Selected References
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- ADAMSTONE F. B., SPECTOR H. Tryptophan deficiency in the rat; histologic changes induced by forced feeding of acid-hydrolyzed casein diet. AMA Arch Pathol. 1950 Feb;49(2):173-84, illust. [PubMed] [Google Scholar]
- Blobel G., Potter V. R. Studies on free and membrane-bound ribosomes in rat liver. II. Interaction of ribosomes and membranes. J Mol Biol. 1967 Jun 14;26(2):293–301. doi: 10.1016/0022-2836(67)90298-7. [DOI] [PubMed] [Google Scholar]
- CAMMARANO P., GIUDICE G., LUKES B. POLYRIBOSOMES IN REGENERATING LIVER. Biochem Biophys Res Commun. 1965 May 3;19:487–493. doi: 10.1016/0006-291x(65)90151-8. [DOI] [PubMed] [Google Scholar]
- Cammarano P., Chinali G., Gaetani S., Spadoni M. A. Involvement of adrenal steroids in the changes of polysome organization during feeding of unbalanced amino acid diets. Biochim Biophys Acta. 1968 Jan 29;155(1):302–304. doi: 10.1016/0005-2787(68)90362-6. [DOI] [PubMed] [Google Scholar]
- DAVIES J. N. Nutrition and nutritional diseases. Annu Rev Med. 1952;3:99–132. doi: 10.1146/annurev.me.03.020152.000531. [DOI] [PubMed] [Google Scholar]
- Farber E. Biochemical pathology. Annu Rev Pharmacol. 1971;11:71–96. doi: 10.1146/annurev.pa.11.040171.000443. [DOI] [PubMed] [Google Scholar]
- Fleck A., Shepherd J., Munro H. N. Protein synthesis in rat liver: influence of amino acids in diet on microsomes and polysomes. Science. 1965 Oct 29;150(3696):628–629. doi: 10.1126/science.150.3696.628. [DOI] [PubMed] [Google Scholar]
- GARROW J. S. The effect of protein depletion on the distribution of protein synthesis in the dog. J Clin Invest. 1959 Jul;38(7):1241–1250. doi: 10.1172/JCI103899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GELBOIN H. V., SOKOLOFF L. Effects of 3-methylcholanthrene and phenobarbital on amino acid incorporation into protein. Science. 1961 Sep 1;134(3479):611–612. doi: 10.1126/science.134.3479.611. [DOI] [PubMed] [Google Scholar]
- GUIDOTTI G. G., ROSSI C. B., RAGNOTTI G. AMINO ACID INCORPORATION INTO PROTEIN OF HEPATIC TISSUE IN CLOUDY SWELLING. Proc Soc Exp Biol Med. 1963 Nov;114:308–313. doi: 10.3181/00379727-114-28660. [DOI] [PubMed] [Google Scholar]
- Ganoza M. C., Williams C. A. In vitro synthesis of different categories of specific protein by membrane-bound and free ribosomes. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1370–1376. doi: 10.1073/pnas.63.4.1370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hallinan T., Murty C. N., Grant J. H. The exclusive function of reticulum bound ribosomes in glycoprotein biosynthesis. Life Sci. 1968 Mar 15;7(6):225–232. doi: 10.1016/0024-3205(68)90016-7. [DOI] [PubMed] [Google Scholar]
- Henderson A. R. The effect of feeding with a tryptophan-free amino acid mixture on rat liver magnesium ion-activated deoxyribonucleic acid-dependent ribonucleic acid polymerase. Biochem J. 1970 Nov;120(1):205–214. doi: 10.1042/bj1200205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hicks S. J., Drysdale J. W., Munro H. N. Preferential synthesis of ferritin and albumin by different populations of liver polysomes. Science. 1969 May 2;164(3879):584–585. doi: 10.1126/science.164.3879.584. [DOI] [PubMed] [Google Scholar]
- Hidvégi E. J., Holland J., Bölöni E., Lónai P., Antoni F., Várterész V. The effect of whole-body x-irradiation of guinea pigs on liver ribosomes. Biochem J. 1968 Oct;109(4):495–505. doi: 10.1042/bj1090495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hori M., Fisher J. M., Rabinovitz M. Tryptophan deficiency in rabbit reticulocytes: polyribosomes during interrupted growth of hemoglobin chains. Science. 1967 Jan 6;155(3758):83–84. doi: 10.1126/science.155.3758.83. [DOI] [PubMed] [Google Scholar]
- Hunt R. T., Hunter A. R., Munro A. J. The control of haemoglobin synthesis: factors controlling the output of alpha and beta chains. Proc Nutr Soc. 1969 Sep;28(2):248–254. doi: 10.1079/pns19690046. [DOI] [PubMed] [Google Scholar]
- Jefferson L. S., Korner A. Influence of amino acid supply on ribosomes and protein synthesis of perfused rat liver. Biochem J. 1969 Mar;111(5):703–712. doi: 10.1042/bj1110703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jorgensen A. J., Majumdar A. P. Bilateral adrenalectomy: effect of a single tube-feeding of tryptophan on amino acid incorporation into plasma abumin and fibrinogen in vivo. Biochem Med. 1975 Jul;13(3):231–240. doi: 10.1016/0006-2944(75)90080-0. [DOI] [PubMed] [Google Scholar]
- KORNER A. The role of the adrenal gland in the control of amino acid incorporation into protein of isolated rat liver microsomes. J Endocrinol. 1960 Nov;21:177–189. doi: 10.1677/joe.0.0210177. [DOI] [PubMed] [Google Scholar]
- Kaufmann E., Sidransky N., Shinozuka H. Incorporation of 14C-orotic acid into RNA of different-sized nucleoli of rat livers following partial hepatectomy or after force-feeding a threoninedevoid diet. Exp Cell Res. 1969 Apr;55(1):130–132. doi: 10.1016/0014-4827(69)90468-6. [DOI] [PubMed] [Google Scholar]
- LEON H. A., ARRHENIUS E., HULTIN T. Effects of glucocorticoid administration on the incorporation of labelled amino acids into protein by cell-free rat-liver systems. Biochim Biophys Acta. 1962 Oct 8;63:423–433. doi: 10.1016/0006-3002(62)90106-3. [DOI] [PubMed] [Google Scholar]
- Lucas-Lenard J. Protein biosynthesis. Annu Rev Biochem. 1971;40:409–448. doi: 10.1146/annurev.bi.40.070171.002205. [DOI] [PubMed] [Google Scholar]
- Lynn J. K., Sarma D. S., Sidransky H. Response of hepatic polyribosomes of the mouse to the administration of anisotonic solutions. Life Sci II. 1971 Apr 8;10(7):385–394. doi: 10.1016/0024-3205(71)90049-x. [DOI] [PubMed] [Google Scholar]
- Lynn J. K., Sidransky H. Effect of changes of osmotic pressure of portal blood on hepatic protein synthesis. Lab Invest. 1974 Oct;31(4):332–339. [PubMed] [Google Scholar]
- Murty C. N., Sidransky H. The effect of tryptophan on messenger RNA of the liver of fasted mice. Biochim Biophys Acta. 1972 Mar 24;262(3):328–335. doi: 10.1016/0005-2787(72)90270-5. [DOI] [PubMed] [Google Scholar]
- Murty C. N., Verney E., Sidransky H. Effect of tryptophan on polyriboadenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver. Lab Invest. 1976 Jan;34(1):77–85. [PubMed] [Google Scholar]
- Murty C. N., Verney E., Sidransky H. Initiation factors in protein synthesis of liver and skeletal muscle of rats force-fed a threonine-devoid diet. Proc Soc Exp Biol Med. 1974 Jan;145(1):74–79. doi: 10.3181/00379727-145-37751. [DOI] [PubMed] [Google Scholar]
- NIMNI M. E., BAVETTA L. A. Dietary composition and tissue protein synthesis. I. Effect of tryptophan deficiency. Proc Soc Exp Biol Med. 1961 Oct;108:38–43. doi: 10.3181/00379727-108-26838. [DOI] [PubMed] [Google Scholar]
- Oratz M., Rothschild M. A., Schreiber S. S. Effect of dextran infusions on protein synthesis by hepatic microsomes. Am J Physiol. 1970 Apr;218(4):1108–1112. doi: 10.1152/ajplegacy.1970.218.4.1108. [DOI] [PubMed] [Google Scholar]
- Oravec M., Korner A. Stimulation of ribosomal and DNA-like RNA synthesis by tryptophan. Biochim Biophys Acta. 1971 Oct;247(3):404–407. doi: 10.1016/0005-2787(71)90025-6. [DOI] [PubMed] [Google Scholar]
- Oravec M., Sourkes T. L. Inhibition of hepatic protein synthesis by alpha-methyl-DL-tryptophan in vivo. Further studies on the glyconeogenic action of alpha-methyltryptophan. Biochemistry. 1970 Oct 27;9(22):4458–4464. doi: 10.1021/bi00824a030. [DOI] [PubMed] [Google Scholar]
- Peña A., Dvorkin B., White A. Effects of a single injection of cortisol on amino acid-incorporating activities of rat liver and thymic preparations in vitro. J Biol Chem. 1966 May 10;241(9):2144–2150. [PubMed] [Google Scholar]
- Pronczul A. W., Baliga B. S., Triant J. W., Munro H. N. Comparaison of the effect of amino acid supply on hepatic polysome profiles in vivo and in vitro. Biochim Biophys Acta. 1968 Mar 18;157(1):204–206. doi: 10.1016/0005-2787(68)90281-5. [DOI] [PubMed] [Google Scholar]
- ROTHSCHILD M. A., ORATZ M., WIMER E., SCHREIBER S. S. Studies on albumin synthesis: the effects of dextran and cortisone on albumin metabolism in rabbits studied with albumin-I-131. J Clin Invest. 1961 Mar;40:545–554. doi: 10.1172/JCI104282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rothschild M. A., Oratz M., Mongelli J., Fishman L., Schreiber S. S. Amino acid regulation of albumin synthesis. J Nutr. 1969 Aug;98(4):395–403. doi: 10.1093/jn/98.4.395. [DOI] [PubMed] [Google Scholar]
- Rothschild M. A., Oratz M., Mongelli J., Schreiber S. S. Alcohol-induced depression of albumin synthesis: reversal by tryptophan. J Clin Invest. 1971 Sep;50(9):1812–1818. doi: 10.1172/JCI106672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SIDRANSKY H., BABA T. Chemical pathology of acute amino acid deficiencies. III. Morphologic and biochemical changes in young rats fed valine- or lysine-devoid diets. J Nutr. 1960 Apr;70:463–483. doi: 10.1093/jn/70.4.463. [DOI] [PubMed] [Google Scholar]
- SIDRANSKY H., BABA T. Chemical pathology of acute amino acid deficiencies. III. Morphologic and biochemical changes in young rats fed valine- or lysine-devoid diets. J Nutr. 1960 Apr;70:463–483. doi: 10.1093/jn/70.4.463. [DOI] [PubMed] [Google Scholar]
- SIDRANSKY H., FARBER E. Chemical pathology of acute amino acid deficiencies. I. Morphologic changes in immature rats fed threonine-, methionine-, or histidine-devoid diets. AMA Arch Pathol. 1958 Aug;66(2):119–134. [PubMed] [Google Scholar]
- SIDRANSKY H., FARBER E. Chemical pathology of acute amino acid deficiencies. II. Biochemical changes in rats fed threonine-or methionine-devoid diets. AMA Arch Pathol. 1958 Aug;66(2):135–149. [PubMed] [Google Scholar]
- SIDRANSKY H., RECHCIGL M., Jr Chemical pathology of acute amino acid deficiencies. V. Comparison of morphologic and biochemical changes in young rats fed protein-free or threonine-free diets. J Nutr. 1962 Nov;78:269–277. doi: 10.1093/jn/78.3.269. [DOI] [PubMed] [Google Scholar]
- SIDRANSKY H., STAEHELIN T., VERNEY E. PROTEIN SYNTHESIS ENHANCED IN THE LIVER OF RATS FORCE-FED A THREONINE-DEVOID DIET. Science. 1964 Nov 6;146(3645):766–768. doi: 10.1126/science.146.3645.766. [DOI] [PubMed] [Google Scholar]
- SIDRANSKY H., VERNEY E. CHEMICAL PATHOLOGY OF ACUTE AMINO ACID DEFICIENCIES. VI. INFLUENCE OF FAT INTAKE ON THE MORPHOLOGIC AND BIOCHEMICAL CHANGES IN YOUNG RATS FORCE-FED A THREONINE-DEVOID DIET. J Nutr. 1964 Feb;82:269–276. doi: 10.1093/jn/82.2.269. [DOI] [PubMed] [Google Scholar]
- SIDRANSKY H., VERNEY E. CHEMICAL PATHOLOGY OF ACUTE AMINO ACID DEFICIENCIES. VII. MORPHOLOGIC AND BIOCHEMICAL CHANGES IN YOUNG RATS FORCE-FED ARGININE-, LEUCINE-, ISOLEUCINE-, OR PHENYLALANINE-DEVOID DIETS. Arch Pathol. 1964 Aug;78:134–148. [PubMed] [Google Scholar]
- Sarma D. S., Bongiorno M., Verney E., Sidransky H. Effect of oral administration of tryptophan or water on hepatic polyribosomal disaggregation due to puromycin. Exp Mol Pathol. 1973 Aug;19(1):23–35. doi: 10.1016/0014-4800(73)90037-3. [DOI] [PubMed] [Google Scholar]
- Shinozuka H., Verney E., Sidransky H. Alterations in the liver due to acute amino acid deficiency. An electron microscopic study of young rats force-fed a threonine-devoid diet. Lab Invest. 1968 Jan;18(1):72–85. [PubMed] [Google Scholar]
- Sidransky H., Verney E. Decreased protein synthesis in the skeletal muscle of rats force-fed a threonine-devoid diet. Biochim Biophys Acta. 1967 Apr 18;138(2):426–429. doi: 10.1016/0005-2787(67)90503-5. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Effect of diet and tryptophan on hepatic polyribosomal disaggregation due to actinomycin D. Exp Mol Pathol. 1972 Oct;17(2):233–248. doi: 10.1016/0014-4800(72)90072-x. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Enhanced hepatic protein synthesis in rats force-fed a tryptophan-devoid diet. Proc Soc Exp Biol Med. 1970 Dec;135(3):618–622. doi: 10.3181/00379727-135-35107. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Influence of quantity of diet on protein synthesis of rats force-fed a threonine-devoid diet. Lab Invest. 1975 Jan;32(1):65–70. [PubMed] [Google Scholar]
- Sidransky H., Verney E., Murty C. N. Effect of tryptophan on hepatic polyribosomal disaggregation due to hypertonic sodium chloride. Lab Invest. 1976 Mar;34(3):291–297. [PubMed] [Google Scholar]
- Sidransky H., Verney E., Murty C. N. Studies on mRNA of the livers of rats force-fed a threonine-devoid or complete diet. J Nutr. 1974 Jun;104(6):726–732. doi: 10.1093/jn/104.6.726. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E., Sarma D. S. Effect of tryptophan on hepatic polyribosomal disaggregation due to ethionine. Proc Soc Exp Biol Med. 1972 Jun;140(2):633–637. doi: 10.3181/00379727-140-36519. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E., Sarma D. S. Effect of tryptophan on polyribosomes and protein synthesis in liver. Am J Clin Nutr. 1971 Jul;24(7):779–785. doi: 10.1093/ajcn/24.7.779. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Skeletal muscle protein metabolism changes in rats force-fed a diet inducing an experimental Kwashiorkor-like model. Am J Clin Nutr. 1970 Sep;23(9):1154–1159. doi: 10.1093/ajcn/23.9.1154. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Studies on hepatic polyribosomes and protein synthesis in rats force-fed a protein-free diet. J Nutr. 1971 Sep;101(9):1153–1164. doi: 10.1093/jn/101.9.1153. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Verney E. Studies on hepatic protein synthesis in rats force-fed a threonine-devoid diet. Exp Mol Pathol. 1970 Aug;13(1):12–24. doi: 10.1016/0014-4800(70)90081-x. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Wagle D. S., Bongiorno M., Verney E. Chemical pathology of acute amino acid deficiencies: Studies on hepatic enzymes in rats force-fed a threonine-devoid diet. J Nutr. 1970 Jun;100(6):678–684. doi: 10.1093/jn/100.6.678. [DOI] [PubMed] [Google Scholar]
- Sidransky H., Wagle D. S., Bongiorno M., Verney E. Studies on blood glucose and hepatic glycogen in rats force-fed a threonine-devoid diet. J Nutr. 1969 Aug;98(4):477–485. doi: 10.1093/jn/98.4.477. [DOI] [PubMed] [Google Scholar]
- Sidransky J., Verney E., Shinozuka H. Alterations in distribution of free and membrane-bound ribosomes in the liver of rats force-fed a threonine-devoid diet. Exp Cell Res. 1969 Jan;54(1):37–41. doi: 10.1016/0014-4827(69)90289-4. [DOI] [PubMed] [Google Scholar]
- Sox H. C., Jr, Hoagland M. B. Functional alterations in rat liver polysomes associated with starvation and refeeding. J Mol Biol. 1966 Sep;20(1):113–121. doi: 10.1016/0022-2836(66)90121-5. [DOI] [PubMed] [Google Scholar]
- Staehelin T., Verney E., Sidransky H. The influence of nutritional change on polyribosomes of the liver. Biochim Biophys Acta. 1967 Aug 22;145(1):105–119. doi: 10.1016/0005-2787(67)90659-4. [DOI] [PubMed] [Google Scholar]
- VAN PILSUM J. F., SPEYER J. F., SAMUELS L. T. Essential amino acid deficiency and enzyme activity. Arch Biochem Biophys. 1957 May;68(1):42–53. doi: 10.1016/0003-9861(57)90325-9. [DOI] [PubMed] [Google Scholar]
- Verney E., Sidransky H. Alterations in cardiac protein metabolism in rats force-fed a threonine-devoid diet. J Nutr. 1974 Apr;104(4):463–472. doi: 10.1093/jn/104.4.463. [DOI] [PubMed] [Google Scholar]
- Verney E., Sidransky H. Protein synthesis in rats force-fed for one day purified diets containing complete, threonine-devoid or no amino acids and adequate or low carbohydrate. Exp Mol Pathol. 1975 Feb;22(1):85–97. doi: 10.1016/0014-4800(75)90054-4. [DOI] [PubMed] [Google Scholar]
- WAGLE D. S., SIDRANSKY H. EFFECT OF ADRENALECTOMY ON PATHOLOGIC CHANGES IN RATS FORCE-FED A THREONINE-DEVOID DIET. Metabolism. 1965 Aug;14:932–939. doi: 10.1016/0026-0495(65)90133-2. [DOI] [PubMed] [Google Scholar]
- WAGLE S. R. THE INFLUENCE OF GROWTH HORMONE, CORTISOL AND INSULIN ON THE INCORPORATION OF AMINO ACIDS INTO PROTEIN. Arch Biochem Biophys. 1963 Sep;102:373–378. doi: 10.1016/0003-9861(63)90244-3. [DOI] [PubMed] [Google Scholar]
- WANNEMACHER R. W., Jr Incorporation of S35 from L-methionine in tumor-bearing and protein-depleted rats. Proc Soc Exp Biol Med. 1961 Jun;107:277–280. doi: 10.3181/00379727-107-26601. [DOI] [PubMed] [Google Scholar]
- WATERLOW J. Effect of protein depletion on the distribution of protein synthesis. Nature. 1959 Dec 12;184(Suppl 24):1875–1876. doi: 10.1038/1841875a0. [DOI] [PubMed] [Google Scholar]
- Webb T. E., Blobel G., Potter V. R. Polyribosomes in rat tissues. 3. The response of the polyribosome pattern of rat liver to physiologic stress. Cancer Res. 1966 Feb;26(2):253–257. [PubMed] [Google Scholar]
- Wittman J. S., 3rd, Lee K. L., Miller O. N. Dietary and hormonal influences on rat liver polysome profiles; fat, glucose and insulin. Biochim Biophys Acta. 1969 Feb 18;174(2):536–543. doi: 10.1016/0005-2787(69)90282-2. [DOI] [PubMed] [Google Scholar]
- Wunner W. H. The time sequence of RNA and protein synthesis in cellular compartments following an acute dietary challenge with amino acid mixtures. Proc Nutr Soc. 1967;26(2):153–162. doi: 10.1079/pns19670032. [DOI] [PubMed] [Google Scholar]
- von der DECKEN, HULTIN T. Inductive effects of 3-methyl-cholanthrene on enzyme activities and amino acid incorporation capacity of rat liver microsomes. Arch Biochem Biophys. 1960 Oct;90:201–207. doi: 10.1016/0003-9861(60)90568-3. [DOI] [PubMed] [Google Scholar]
