Summary
In the serum of rats with liver cirrhosis induced by 12-week intermittent carbon tetrachloride (CCl4) injection, free L-tryptophan (Trp) levels increased with decreases in total Trp, albumin-bound Trp, and albumin levels. In the serum of the cirrhotic rats, there were no changes in the ratio of albumin-bound Trp to albumin and the level of free fatty acids which are known to weaken the binding of Trp to albumin. In the liver of the cirrhotic rats, there were increases in protein and free Trp (i.e., non-protein Trp) contents and a decrease in total tryptophan 2,3-dioxygenase (TDO) activity. The decreased TDO activity was mainly due to the reduction of apo-TDO activity. When [3H]Trp was injected into the portal vein of the cirrhotic and control rats, radioactivity derived from the injected [3H]Trp in the liver was higher in the cirrhotic rats than in the control rats at 10min after the injection, while the radioactivity in the serum was lower in the former rats than in the latter rats. These results indicate that the increased Trp is easily taken up into the cirrhotic liver, and suggest that the Trp taken up into the cirrhotic liver could be utilized for the maintenance of synthesis of proteins in the tissue through the reduction of Trp metabolism due to reduced TDO activity in the tissue.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bender DA (1982) Biochemistry of tryptophan in health and disease. Mol Aspect Med 6: 101–197
Bondjers G, Björkerud S (1973) Spectrophotometric determination of hydroxyproline in connective tissue on the nanogram level. Anal Biochem 52: 496–504
Brodersen R, Vorum H, Skribver E, Pederson AO (1989) Serum albumin binding of palmitate and stearate. Multiple binding theory for insolbule ligands. Eur J Biochem 182: 19–25
Cangiano C, Calaterra V, Cascino A, Capocaccia L (1976) Bound and free tryptophan plasma levels in hepatic encephalopathy. Rendie Gastroenterol 8: 186–189
Curzon G, Friedel J, Knott PJ (1973) The effect of albumin binding and amino acid competition to plasma protein. Nature 242: 198–200
Curzon G, Friedel J, Katamaneni BD, Greenwood MH, Lader MH (1974) Unesterified fatty acids and the binding of tryptophan in human plasma. Clin Sci Mol Med 47: 415–424
Doumas BT, Watson A, Biggs HG (1971) Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta 31: 87–96
Fuller RW, Roush BW (1973) Binding of tryptophan to plasma proteins in several species. Comp Biochem Pysiol 46B: 273–276
Gornal AG, Bardawill CS, David MM (1949) Determination of serum proteins by means of the Biuret reaction. J Biol Chem 177: 751–766
Hasch E, Jarnum S, Tygstrup N (1967) Albumin synthesis rate as a measure of liver function in patients with cirrhosis. Acta Med Scand 182: 83–92
Hijita Y, Hara K, Egawa H, Mizuno T, Shiozaki Y, Murata K, Sameshima Y (1981) Microdetermination of unbound tryptophan in plasma by a combination of ultrafiltration and high-performance liquid chromatography. Anal Biochem 118: 10–16
Huberman A, Soberon G (1970) Albumin synthesis in liver slices of cirrhotic rats. Clin Chim Acta 29: 121–127
Kershenobich D, Rojkind M (1973) Effect of the administration of L-azetidine-2-carboxylic acid on albumin and transferrin biosynthesis by liver slices of rats treated with carbon tetrachloride. Biochim Biophys Acta 319: 216–222
Knox WE, Piras MM, Tokuyama K (1966) Tryptophan pyrrolase of liver. J Biol Chem 241: 297–303
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 183: 265–275
McMenamy RH, Lund CC, Oncley JL (1957) Unbound amino acid concentration in human blood plasma. J Clin Invest 36: 1672–1679
McMenamy RH, Oncley JL (1958) The specific binding of L-tryptophan to serum albumin. J Biol Chem 233: 1436–1447
Panduro A, Shalaby F, Biempica L, Shafritz DA (1988) Changes in albumin,α-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis. Hepatology 8: 259–266
Rocchi E, Farina F, Silingardi M, Casalgrandi G (1986) High-performance liquid chromatographic determination of total and free tryptophan in serum from control subjects and liver patients. J Chromatogr 380: 128–132
Rothschild MA, Oratz M, Mongelli J, Fishman L, Schreiber SS (1969a) Amino acid regulation of albumin synthesis. J Nutr 98: 395–403
Rothschild MA, Oratz M, Zimmon D, Schreiber SS, Weiner I, Van Caneghem A (1969b) Albumin synthesis in cirrhotic subjects with ascites studied with carbonate-14C. J Clin Invest 48: 344–350
Saito K, Sasaki E, Ohta Y, Nagamura Y, Ishiguro I (1986) Mode of L-tryptophan uptake into rat hepatocytes via trypsin-sensitive high-affinity transport system. Biochem Int 13: 873–883
Salter M, Knowles RG, Pogson CI (1986) Transport of the aromatic amino acids into isolated rat liver cells. Biochem J 233: 499–506
Sasaki E, Ohta Y, Shinohara R, Ishiguro I (1993) Effect of serum free fatty acid levels on disappearance of blood L-tryptophan in rats fed lard. J Jpn Soc Nutr Food Sci (Nippon Eiyo Shokuyro Gakkaishi) 46: 487–493
Sato Y, Maruyama M (1972) The inhibition of tryptophan pyrrolase synthesis in rat liver by carbon tetrachloride. J Biochem 72: 1129–1137
Sidransky H (1985) Tryptophan. Unique action by an essential amino acid. In: Sidransky H (ed) Nutritional pathology. Pathobiochemistry of dietary imbalance. Dekker, New York, pp 1–62
Sidransky H, Verney E, Kurl RN, Razavi T (1988) Effect of tryptophan on toxic cirrhosis induced by intermittent carbon tetrachloride intoxication in the rat. Exp Mol Pathol 49: 102–110
Uemura M, Saito K, Ohta Y, Ishiguro I, Ito M, Nagamura Y (1989) The relationship between tryptophan level in serum and its hepatic uptake in rats with injured liver by carbon tetrachloride. Jpn J Clin Chem (Rinsho Kagaku) 17: 147–153
Yoshida K, Hirayama C (1980) Clinical evaluation of serum levels of tryptophan in hepatobillary disease. Clin Chim Acta 101: 235–240
Zoli M, Marchesini G, Cecchini L, Dondi C, Bianchi FB, Pisi E (1981) Binding of tryptophan to albumin in liver cirrhosis. A reappraisal of the problem. Hepatogastroenterology 28: 87–89
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ohta, Y., Uemura, M., Saito, K. et al. Relationship between the level of serum L-tryptophan and its hepatic uptake and metabolism in rats with carbon tetrachloride-induced liver cirrhosis. Amino Acids 10, 369–378 (1996). https://doi.org/10.1007/BF00805864
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00805864