Abstract
Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Benson J. V., Jr, Patterson J. A. Accelerated chromatographic analysis of amino acids commonly found in physiological fluids on a spherical resin of specific design. Anal Biochem. 1965 Nov;13(2):265–280. doi: 10.1016/0003-2697(65)90196-x. [DOI] [PubMed] [Google Scholar]
- Branch R. A., Herbert C. M., Read A. E. Determinants of serum antipyrine half-lives in patients with liver disease. Gut. 1973 Jul;14(7):569–573. doi: 10.1136/gut.14.7.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broadus A. E., Kaminsky N. I., Hardman J. G., Sutherland E. W., Liddle G. W. Kinetic parameters and renal clearances of plasma adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2222–2236. doi: 10.1172/JCI106441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capocaccia L., Cangiano C., Attili A. F., Angelico M., Cascino A., Rossi Fanelli F. Octopamine and ammonia plasma levels in hepatic encephalopathy. Clin Chim Acta. 1977 Feb 15;75(1):99–105. doi: 10.1016/0009-8981(77)90504-6. [DOI] [PubMed] [Google Scholar]
- Cheung M. C., Slaunwhite W. R., Jr Use of polyethylene glycol in separating bound from unbound ligand in radioimmunoassay of thyroxine. Clin Chem. 1976 Mar;22(3):299–304. [PubMed] [Google Scholar]
- David J. C., Dairman W., Udenfriend S. Decarboxylation to tyramine: a major route of tyrosine metabolism in mammals. Proc Natl Acad Sci U S A. 1974 May;71(5):1771–1775. doi: 10.1073/pnas.71.5.1771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FORMAN D. T. RAPID DETERMINATION OF PLASMA AMMONIA BY AN ION-EXCHANGE TECHNIC. Clin Chem. 1964 Jun;10:497–508. [PubMed] [Google Scholar]
- Faraj B. A., Bowen P. A., Isaacs J. W., Rudman D. Hypertyraminemia in cirrhotic patients. N Engl J Med. 1976 Jun 17;294(25):1360–1364. doi: 10.1056/NEJM197606172942502. [DOI] [PubMed] [Google Scholar]
- Faraj B. A., Dayton P. G., Camp V. M., Wilson J. P., Malveaux E. F., Schlant R. C. Studies of the fate of tyramine in dogs: the effect of monoamine oxidase inhibition, portafemoral shunt and coronary artery ligation on the kinetics of tyramine. J Pharmacol Exp Ther. 1977 Feb;200(2):384–393. [PubMed] [Google Scholar]
- Faraj B. A., Mu J. Y., Lewis M. S., Wilson J. P., Israili Z. H., Dayton P. G. Determination of plasma and tissue levels of tyramine by radioimmunoassay. Proc Soc Exp Biol Med. 1975 Jul;149(3):664–669. doi: 10.3181/00379727-149-38875. [DOI] [PubMed] [Google Scholar]
- Fischer J. E., Baldessarini R. J. False neurotransmitters and hepatic failure. Lancet. 1971 Jul 10;2(7715):75–80. doi: 10.1016/s0140-6736(71)92048-4. [DOI] [PubMed] [Google Scholar]
- Fischer J. E., Yoshimura N., Aguirre A., James J. H., Cummings M. G., Abel R. M., Deindoerfer F. Plasma amino acids in patients with hepatic encephalopathy. Effects of amino acid infusions. Am J Surg. 1974 Jan;127(1):40–47. doi: 10.1016/0002-9610(74)90009-9. [DOI] [PubMed] [Google Scholar]
- Kiefer E. F. A rapid, convenient preparative procedure for phenethylamines. J Med Chem. 1972 Feb;15(2):214–214. doi: 10.1021/jm00272a029. [DOI] [PubMed] [Google Scholar]
- Lam K. C., Tall A. R., Goldstein G. B., Mistilis S. P. Role of a false neurotransmitter, octopamine, in the pathogenesis of hepatic and renal encephalopathy. Scand J Gastroenterol. 1973;8(6):465–472. [PubMed] [Google Scholar]
- Levine R. J., Conn H. O. Tyrosine metabolism in patients with liver disease. J Clin Invest. 1967 Dec;46(12):2012–2020. doi: 10.1172/JCI105690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manghani K. K., Lunzer M. R., Billing B. H., Sherlock S. Urinary and serum octopamine in patients with portal-systemic encephalopathy. Lancet. 1975 Nov 15;2(7942):943–946. doi: 10.1016/s0140-6736(75)90359-1. [DOI] [PubMed] [Google Scholar]
- Nordlinger B. M., Fulenwider J. T., Faraj B. A., Bethel R. A., Rudman D. Tyrosine metabolism in cirrhosis: acquired alkaptonuria. Surg Forum. 1978;29:442–444. [PubMed] [Google Scholar]
- PARSONS-SMITH B. G., SUMMERSKILL W. H., DAWSON A. M., SHERLOCK S. The electroencephalograph in liver disease. Lancet. 1957 Nov 2;273(7001):867–871. doi: 10.1016/s0140-6736(57)90005-3. [DOI] [PubMed] [Google Scholar]
- Rikkers L., Jenko P., Rudman D., Freides D. Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology. 1978 Sep;75(3):462–469. [PubMed] [Google Scholar]
- Sherwin R., Joshi P., Hendler R., Felig P., Conn H. O. Hyperglucagonemia in Laennec's cirrhosis. The role of portal-systemic shunting. N Engl J Med. 1974 Jan 31;290(5):239–242. doi: 10.1056/NEJM197401312900502. [DOI] [PubMed] [Google Scholar]
- Tygstrup N. Determination of the hepatic elimination capacity (Lm) of galactose by single injection. Scand J Clin Lab Invest Suppl. 1966;18:118–125. [PubMed] [Google Scholar]
- Zinneman H. H., Seal U. S., Doe R. P. Plasma and urinary amino acids in Laennec's cirrhosis. Am J Dig Dis. 1969 Feb;14(2):118–126. doi: 10.1007/BF02232835. [DOI] [PubMed] [Google Scholar]
