Zusammenfassung
Hauptaufgabe des Darms ist die Resorption von Nahrungsbestandteilen bei gleichzeitiger Abwehr von Mikroorganismen, Toxinen oder gefährlichen Antigenen. Aufgrund des sehr hohen Kalorienbedarfs und Eiweißumsatzes ist der Gastrointestinaltrakt auch von zentraler Bedeutung für den intrinsischen Substratstoffwechsel des Körpers. Eine Abhängigkeit intestinaler Stoffwechselleistungen von der Kalorien- und Substratzufuhr ist durch die Krankheitsbilder des Marasmus (chronisches Kaloriendefizit) und Kwashiorkor (chronisches Eiweißdefizit) belegt. Die genaue Regulation durch Substrate, Hormone bzw. unterschiedliche Ernährungsmodalitäten ist bis heute nur unvollkommen verstanden. Die Analyse physiologischer Untersuchungen an Großtieren bzw. Menschen zeigt, dass die metabolische Reaktionsbereitschaft des Intestinums bei jungen Organismen am höchsten ist. Im Erwachsenenalter spielen luminale Proteine eine zentrale Rolle bei der Bewahrung des intestinalen Eiweißbestandes durch Reduktion der Proteinabbaurate. Eine Steigerung der Proteinsyntheserate ist bei luminaler Ernährung nur durch Zufuhr freier Aminosäuren möglich. Auch bei ausschließlich parenteraler Ernährung ist am Menschen über längere Zeiträume (1 - 2 Monate) eine weitgehende Bewahrung des intestinalen Eiweißbestandes zu erreichen. Dabei spielen ebenfalls Aminosäuren die Hauptrolle, wobei jedoch anabole Effekte auf den intestinalen Eiweißabbau bzw. die Eiweißsynthese speziesspezifisch zu sein scheinen. Kohlenhydrate sind für die Aufrechterhaltung der intestinalen Eiweißmasse wahrscheinlich sekundär, ein ausgeprägter anaboler Effekt ist jedoch durch eine gleichzeitige Erhöhung des intestinalen Aminosäure- und Insulinangebots möglich. Eine ausschließliche, längerfristige Kohlenhydratzufuhr kann über die Abwesenheit luminalen Eiweißes und über die Reduktion des arteriellen Aminosäureangebots (durch insulininduzierte Hemmung der muskulären Proteolyse) einen ausgeprägten intestinalen Eiweißmangel hervorrufen, der die schwereren Funktionsveränderungen bei Kwashiorkor (im Vergleich zum Marasmus) erklären könnte. Einschränkend muss jedoch festgestellt werden, dass die meisten Substrat-Darm-Interaktionen an gesunden oder weitgehend gesunden Organismen beschrieben wurden. Entsprechende Regulationsmechanismen bei schwerkranken oder stark mangelernährten Individuen sind bis heute nicht untersucht.
Abstract
Main functions of the gut include absorption of nutrients and simultaneous defense against microorganisms, toxins or dangerous antigens. Because of its very high energy needs and protein turnover the gut plays a central role for regulation of the body's substrate metabolism. Clinical entities such as marasmus (chronic calory deficit) or kwashiorkor (chronic protein deficit) indicate intestinal metabolic functions to depend on an adequate substrate or calory supply. However, exact control mechanisms by specific substrates, hormones or different types of nutrition are still poorly understood. Analysis of physiologic experiments in humans or large mammals shows that metabolic reactivity of the gut is the highest when organisms are very young. In adult organisms luminal proteins are of central importance for maintaining the intestinal protein content by their inhibitory action on protein degradation. During luminal nutrition a rise in gut protein synthesis is only possible if free amino acids are being administered. Also with exclusive total parenteral nutrition the intestinal protein content can be largely preserved in humans over prolonged periods of time (one to two months). To do so, amino acids are again of central importance. However, their anabolic effects on gut protein degradation and synthesis appear to be species specific. Carbohydrates are presumably of minor importance for the preservation of gut protein. Nevertheless, a simultaneous rise of amino acid, carbohydrate and insulin supply results in a significant anabolic effect. Preponderant carbohydrate feeding may cause a severe intestinal protein deficit since provision of insufficient luminal protein is combined with an insulin-induced reduction of intestinal arterial amino acid supply (via inhibition of muscle amino acid release). This mechanism may explain why intestinal dysfunction is more pronounced in kwashiorkor than in marasmus. However, most of the substrate-gut interactions have been examined in healthy or mostly healthy organisms. Corresponding regulatory mechanisms in severely ill or malnourished individuals have not yet been studied.
Schlüsselwörter
Intestinaltrakt - Mukosa - Eiweißstoffwechsel - Aminosäuren - Kohlenhydrate - Insulin
Key words
Intestinal tract - mucosa - protein metabolism - amino acids - carbohydrates - insulin
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PD Dr. Wolfgang H. Hartl
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