title: Upper gastrointestinal bleeding: an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule.
abstract: Upper gastrointestinal bleeding causes increased urea concentrations in patients with normal liver function and high ammonia concentrations in patients with impaired liver function. This ammoniagenesis may precipitate encephalopathy. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and has high amounts of leucine and valine. Upper gastrointestinal bleeding therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce a cascade of events culminating in net catabolism. This may influence the function of rapidly dividing cells and short half-life proteins. We hypothesize that, following a variceal bleed in a cirrhotic patient, the lack of isoleucine in blood protein is the cause of the exaggerated ammoniagenesis and catabolism. We propose that intravenous administration of isoleucine may serve as a simple therapeutic that transforms blood protein in a balanced protein, resulting in only a short-lived rise in ammonia and urea production, and preventing interference with protein synthesis.
authors.affiliation: Department of Surgery, Academic Hospital Maastricht, Maastricht University, The Netherlands.
authors.forename: S W
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: C H
authors.initials: CH
authors.lastname: Dejong
authors.forename: N E
authors.initials: NE
authors.lastname: Deutz
authors.forename: C L
authors.initials: CL
authors.lastname: van Berlo
authors.forename: P B
authors.initials: PB
authors.lastname: Soeters
mesh_terms: D000641:Ammonia / Q000097:blood / Q000378:metabolism*; D006471:Gastrointestinal Hemorrhage / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000502:physiology* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications; D008954:Models, Biological; D014508:Urea / Q000097:blood
chemical_list: D006454:Hemoglobins; D007532:Isoleucine; D000641:Ammonia; D014508:Urea