Urinary Excretion of Choline Metabolites Following Choline Administration in Normals and Patients With Hepatobiliary Diseases 1

Abstract

Choline has been recommended for the treatment of hepatic diseases, especially those of nutritional origin, and for the prevention of arteriosclerosis. Little is known of its fate after oral or intravenous administration. A recent Spanish report (1) that patients with liver diseases and dogs with experimental hepatic damage excrete in the urine considerably more than normal of a substance precipitated by Reinecke salt (and considered as choline by the authors) after large doses of choline given orally, suggested that the utilization of choline might be altered in hepatobiliary disease. In addition, studies with radiophosphorous (2) indicate a reduced rate of phospholipid formation in the presence of hepatocellular damage and an increased rate in biliary obstruction, suggesting that less choline might appear in the urine than normal in obstructive jaundice and more than normal in liver cell damage.To test these hypotheses and to investigate the fate of choline after its oral adrministration 1 ) the identity of the reineckate precipitated from the urine was determined, and 2) the influence upon its excretion of physiologic conditions as well as hepatobiliary diseases was studied. MATERIALFour normal subj ects and 22 patients with various hepatobiliary diseases were given on separate occasions single doses of choline bicarbonate3 equivalent to 2-8 grams of choline base (230-920 mg. choline N). Their diets were not controlled. Urine samples, collected at various intervals, were preserved with 25 ml. of concentrated hydrochloric acid (diluted with equal parts of water) per liter of urine.

Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

“…This chemical transformation plays a significant role in many biological systems and impacts both the environment and human health. It has long been recognized that symbiotic gut microbes in humans (9)(10)(11) and other vertebrates (12)(13)(14) generate TMA from choline and that this metabolic activity is exclusively microbial. In humans, TMA is further processed to TMAO by the liver enzyme flavin-dependent monooxygenase 3 (FMO3) (15).…”

The Effects of Antimicrobial Agents Upon Choline Degradation in the Intestinal Tract

“…This is twice the 1 Thanks are due to Commercial Solvents Corporation for the generous supply of choline bicarbonate syrup. amount of choline used in previous studies (3). This large dose of choline was chosen since the use of a larger dose would give a better indication of the depression of trimethylamine formation by the antimicrobial agents.…”

“…When a relatively large amount of choline is ingested by normal persons, about 60 per cent appears in the urine as total trimethylamines (TTMA), mostly within 24 hours (3).…”

“…Part of the evidence gathered to establish this phenomenon was that, following ingestion of choline with aureomycin, much less TTMA than usual were excreted (3,4). Further experiments were undertaken to elaborate upon the inhibition of TTMA formation from choline by antimicrobial agents.…”

Trimethylamin [MAK Value Documentation in German language, 1983]

“…Das umsetzende Enzym, Dimethylanilinmonooxygenase (N-oxide forming, EC 1.14.13.8), kommt auch in der menschlichen Leber vor [6,7]. Trimethylaminoxid, das 20fach weniger toxisch ist als das Amin [8], wird beim Menschen und bei Säugetieren [9,10] fast quantitativ im Harn ausgeschieden [11,12]. Wird das N-Oxidierungssystem gesättigt, kann (bei Hunden und Ratten) nicht metabolisiertes Trimethylamin ausgeschieden werden [13,14].…”