Review Measurement of intestinal protein synthesis by continuous arterial tracer application: Intrinsically difficult problems arising from different protein pools and study techniques q Wolfgang H. Hartl a, * , David H. Alpers b , Bruce W. Patterson c a Department of Surgery, Campus Grosshadern; Ludwig-Maximilian University Munich, Germany b Division of Gastroenterology and Center for Human Nutrition, Washington University School of Medicine, St Louis, MO, USA c Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, Department of Medicine, St. Louis, MO, USA article info Article history: Received 17 September 2009 Accepted 2 March 2010 Keywords: Intestinal mucosa Protein pool Tracer incorporation Enrichment summary Background & aims: During continuous tracer infusion and steady state conditions, it is unclear whether different study designs (single vs. multiple biopsies) will yield identical rates of intestinal protein synthesis. Methods: We reviewed the available literature and used hypothetical pool models to derive protein synthetic rates for different study techniques. Results: There is strong evidence that intestinal mucosa consists of different protein pools with different turnover rates. In the smaller rapid turnover pool, isotopic enrichment during continuous tracer infusion and steady state conditions may reach a plateau after a few hours. There is mathematical evidence, that metabolic effects in the slow turnover pool might be missed, if only a single measurement of mixed mucosal enrichment is performed after a metabolic manipulation, and if this metabolic manipulation and continuous tracer infusion is started simultaneously. Conclusion: True values for protein synthesis in the dominating slow turnover pool will only be obtained, if sequential mucosa enrichments are measured after a plateau has been reached in the rapid turnover pool, and if metabolic manipulations are only started beyond this point. However, this approach precludes the simultaneous registration of metabolic effects in the rapid turnover pool. Ó 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. 1. Introduction During continuous arterial application of an amino acid tracer in a stable metabolic state, the increase of tracer enrichment in the tissue will not be infinitely linear, but the rate of enrichment increase will start to decline after a certain period of time until a plateau is ultimately reached. The point of time beyond which this deceleration occurs depends on the magnitude of tissue turnover. It has been repeatedly observed in tissues with a high turnover rate (>1%/h) that this decline of rate is already detectable after a few hours. Corresponding findings have been made in rat liver, 1e3 and in human small bowel 4 and colorectal cancer. 5 The magnitude of that early decline is so enormous that it cannot be attributed to simultaneous metabolic changes (e.g. fasting). To explain this phenomenon, a concept has been proposed which assumes within one tissue different protein pools with different protein turnover rates and corresponding different speeds of tracer incorporation. 1 The existence of such differing pools of relevant size has been shown in rodent and dog liver, 2,6 and in rodent small intestine 7 and intestinal brush border. 8 There is also evidence for the existence of different protein pools with a variable turnover rate in human small bowel. 4 Turnover of individual proteins in different pools varies between a few minutes and many days. When tracer is given continuously, after a certain amount of time all existing protein in an individual pool will have incorporated the tracer. The amount of time required for this state to be reached can be used to calculate fractional protein synthesis and half life, if turnover and mass remain constant. Thus, after a linear phase with a continuous increase of tracer enrichment, the enrichment in a particular protein will reach a plateau of which the magnitude corresponds to the magnitude of tracer enrichment in the precursor pool. The enrichment measured at a certain time in a mixed protein pool will, q This work was supported by grants from the Deutsche Forschungsgemeinschaft (Ha 1439/4-1). * Correspondence to: Chirurgische Klinik, Klinikum Grosshadern, March- ioninistr.15, D-81377 Munich, Germany. Tel.: þ49 89 7095 3510; fax: þ49 89 700 4418. E-mail address: whartl@med.uni-muenchen.de (W.H. Hartl). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu 0261-5614/$ e see front matter Ó 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. doi:10.1016/j.clnu.2010.04.005 Clinical Nutrition 30 (2011) 28e32