The limitations to using tracers to define amino acid and protein metabolism are largely driven by how the tracer is administered and where it is sampled. The simplest method of tracer administration is orally, but intravenous administration is preferred to deliver the tracer systemically (to the whole body) into the free pool of amino acids. The simplest site of sampling of the tracer dilution is also from the free pool of amino acids via blood. Therefore, most approaches to measuring amino acid and protein kinetics in the whole body using amino acid tracers assume a single, free pool of amino N, as shown in Figure2.10. Amino acids enter the free pool from dietary amino acid intake (enteral or parenteral) and by amino acids released from protein breakdown. Amino acids leave the free pool by amino acid oxidation to end products (CO2, urea, and ammonia) and from amino acid uptake for protein synthesis. The free amino acid pool can be viewed from the standpoint of all of the amino acids together (as discussed for the end-product method) or from the viewpoint of a single amino acid and its metabolism per se. The model in Figure 2...10 is called a "single-pool model" because protein is not viewed as a pool per se, but rather as a source of entry of unlabeled amino acids into the free pool, on the one hand, and a route of amino acid removal for protein synthesis on the other. Only a small portion of the proteins in the body are assumed to turn over during the time course of the experiment. Obviously, these assumptions are not true: many proteins in the body are turning over rapidly (e.g, most enzymes). Proteins that do turn over during the time course of the experiment will become labeled and appear as part of the free amino acid pool. However, these proteins make up only a fraction of the total protein; the remainder turn over slowly (e.g., muscle protein). Most amino acids entering via protein breakdown and leaving for new protein synthesis are coming from slowly turning over proteins. These flows are the B and S arrows of the traditional single-pool model of whole-body protein metabolism shown in FlgMCe,..2 10.
Figure 2.10. Single-pool model of whole-body protein metabolism measured with a labeled amino acid tracer. Amino acid enters the free pool from dietary intake (I) and amino acid released from protein breakdown (B) and leaves the free pool via amino acid oxidation (C) to urea, ammonia, and CO2 and uptake for protein synthesis (S).
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