Hans Krebs and the foundation of the use of glutamine in clinical nutrition: A personal perspective

Malcolm Watford, John T. Brosnan

Research output: Contribution to journalArticlepeer-review

Abstract

This article details the role of Hans Adolf Krebs (Nobel laureate 1953) in the study of glutamine metabolism that set the stage for the use of glutamine in clinical nutrition. The authors have carried out research on glutamine metabolism for many years and both trained under Krebs for the degree of Doctor of Philosophy at the University of Oxford. In 1923, Krebs qualified in medicine and spent three years in clinical training. He began his scientific caieer in the laboratory of Otto Warburg in 1926. Using Warburg manometry, Krebs worked on a number of projects related to degradation reactions in tumors. In 1931 he began to study synthetic reactions and described the urea cycle, the first cyclic biochemical pathway. In 1933 Krebs moved to England where he continued to work on amino acid metabolism and in 1935 he established the first molecular insights into glutamine metabolism in animal tissues that set the stage for the use of glutamine in clinical nutrition. He had identified the hydrolysis of glutamine by glutaminase and shown that there were different tissue isoforms of the enzyme. He described the fundamental regulatory feature of the most widespread "brain-type" glutaminase, that it is product-inhibited by glutamate; he showed that the "liver-type" isoform was not subject to this form of regulation. After the 1935 paper Krebs worked on other aspects of intermediary metabolism but continued to study glutamine, often applying the latest methodological advances. By the early 1970s, Krebs, and his colleagues, had established that glutamine was a good substrate for hepatic gluconeogenesis and urea synthesis, for renal gluconeogenesis and ammoniagenesis, and was a good respiratory substrate for enterocytes of the small intestine. Furthermore, the Krebs group had showed that skeletal muscle released significant amounts of glutamine and had defined the role of the liver in both glutamine utilization and synthesis. At the time of his death (1981) he was still working on the relationship of branched chain amino acids to glutamine metabolism during the past quarter of a century numerous studies, initially from the groups of Wilmore and Fiirst, have been published describing the use of supplemental glutamine in TPN. A number of meta-analyses have been published with most reporting positive effects of glutamine supplementation, although a few have indicated adverse effects in a select group of patients. Thus the use of glutamine in clinical medicine owes a lot to the work of Krebs and his collaborators and trainees. The authors include a section of "Personal Reflections" describing working with Krebs and both are grateful for the training in the art of scientific investigation receveived from Professor Sir Hans A. Krebs, the father of glutamine metabolism.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalChinese Journal of Clinical Nutrition
Volume22
Issue number1
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Nutrition and Dietetics

Keywords

  • Clinical application
  • Glutamine
  • Kreb's cycle

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