Studies in Methionine and Sulfur Metabolism. I. The Fate of Intravenously Administered Methionine, in Normal Individuals and in Patients With Liver Damage 12

Abstract

The cardinal role of the liver in protein and amino acid metabolism has been well established. Consequently, studies of amino acid metabolism occupy a natural and fundamental place in an investigation of metabolic aberrations in hepatic disease. In 1913, Van advantage since this serves as a "label" in the interpretation of the metabolic fate of the administered methionine.In the present study a standard dose of DLmethionine was administered intravenously. Observations were then made on the rate of disappearance of the amino acid from the plasma together with a comparison of the excretion of free methionine and sulfate sulfur before and after the substance was given. Since the racemic DLmethionine was used, it was of interest to follow the metabolism of both isomers. This was made possible by the separate analysis of samples by two micro-organisms, one utilizing only the Lisomer, the other, both D-and L-isomers. METHODSAll patients (veteran and naval personnel) received a standard high protein, high carbohydrate intake over a two-day period preceding the test, during which time all medication was discontinued. They received no food from 8:00 p.m. the preceding night until after the 180-minute blood and urine samples had been obtained. Methionine determinations were made on deproteinized filtrates of plasma obtained from heparinized blood. After removal of a blood sample for determinations of the fasting methionine level, 50 cc. of a 3 per cent DLmethionine solution were injected over a five-minute period. Blood samples were then drawn at 15, 30, 60, 120, and 180 minutes after the injection. Urine samples corresponding to a two-hour period prior to the administration of the test dose of methionine as well as to the subsequent three-hour period were collected and assayed for methionine and, in some cases, sulfate sulfur (both free and total), and total amino nitrogen. This latter constituent will be discussed in a later communication. In several instances, methionine excretion during various periods up to 48 hours after the test dose had been given was measured.Methionine was determined microbiologically using as test organisms Leuconostoc mesenteroides, P-60, for the assay of L-methionine and Lactobacillus fermenti, 36, for 677

Studies on Amino Acid Excretion in Man. Iii. Amino Acid Levels in Plasma and Urine of Normal Men Fed Diets of Varying Protein Content 1

“…The data for leucine reported by the latter investigators were obtained by the oxidative method of Fromegat which, according to Hier et al (22) (23). The present data for free amino acids in plasma agree with the findings of Hier and Bergeim (24) in a group of 33 normal persons, and with the results for valine and histidine reported by Ackermann et al (25).…”

Role of S-adenosyl-L-methionine in liver health and injury

“…In 1948, Kinsell et al 20 demonstrated marked impairment in methionine clearance after a methionine load in patients with liver injury, thereby establishing the central role of the liver in methionine metabolism. Patients with liver cirrhosis have decreased SAMe biosynthesis because of decreased expression of MAT1A and lower hepatic MAT activity, 21,22 and treatment with SAMe increased hepatic GSH levels and increased survival in patients with less advanced alcoholic liver cirrhosis.…”

The Levels of Individual Free Amino Acids in the Plasma of Normal Man at Various Intervals After a High-Protein Meal1

“…That intravenously administered amino acids are rapidly removed by the tissues from the blood stream of the dog was shown many years ago by Van Slyke and Meyer (1,37). In man, also, intravenously administered glycine, methionine and lysine have been found to disappear rapidly (38)(39)(40). When the diet is the source of the additional amino acids, the liver assumes particular importance in their disposal.…”