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Doubly labeled water is water in which both the hydrogen and the oxygen have been partly or completely replaced for tracing purposes (i.e. ''labeled'') with an uncommon isotope of these elements. In practice, for both practical and safety reasons, almost all recent applications of the "doubly labeled water" method use water labeled with the heavy, non-radioactive forms of the elements deuterium and oxygen-18 (O-18 or 18O), or deuterium oxide-18 (D218O). In theory, radioactive forms of hydrogen and oxygen could be used for such labeling, and this was the case in many early applications of the method. In particular, use of the ''doubly labeled water method'' (or DLW method) yields a particular type of measurement of metabolic rate, in which the average metabolic rate of an organism is measured over a period of time. This is done by administering a dose of doubly labeled water, and then measuring the elimination rates of deuterium and O-18 in the subject over time through the regular sampling of heavy isotope concentrations in the body water (by sampling saliva, urine, or blood). The minimum number of samples required is two—an initial sample after the isotopes have reached equilibrium in the body, and a second sample some time later. The time between the collecting of these samples depends on size of the animal involved. In small animals the period may be as short as 24 hours, and in larger animals like adult humans, the period may be as long as 14 days. In animals this average daily metabolic rate measured by the DLW method is often also called the Field metabolic rate or FMR. The method was invented in the 1950s by Nathan Lifson and colleagues〔Lifson, N., Gordon, G.B. and McClintock, R. (1955) Measurement of total carbon dioxide production by means of D218O. J. Appl. Physiol., 7, 704–710.〕〔Lifson, N. and McClintock R. (1966) Theory of use of the turnover rates of body water for measuring energy and material balance. J. Theor. Biol., 12, 46–74.〕 at the University of Minnesota; however, its use was restricted to small animals until the 1980s because of the high cost of the oxygen-18 isotope. Advances in mass spectrometry during the 1970s and early 1980s reduced the amount of isotope required, which made it feasible to apply the method to humans. The first application to humans was in 1982,〔Schoeller, D.A. and van Santen, E. (1982) Measurement of energy expenditure in humans by doubly labelled water. J. Appl. Physiol., 53, 955–959.〕 by Dale Schoeller, over 25 years after the method was initially discovered. A complete summary of the technique is provided in a book by British biologist John Speakman.〔Speakman, J.R., Doubly Labelled Water: Theory and Practice. Springer Scientific publishers. ISBN 0-412-63780-4 ISBN 978-0412637803 416pp)〕 ==Mechanism of the test== The technique measures a subject's carbon dioxide production during the interval between first and last body water samples. The method depends on the details of carbon metabolism in our bodies. When cellular respiration breaks down carbon-containing molecules to release energy, carbon dioxide is released as a byproduct. Carbon dioxide contains two oxygen atoms and only one carbon atom, but food molecules such as carbohydrates do not contain enough oxygen to provide both oxygen atoms found in CO2. It turns out, one of the two oxygen atoms in CO2 is derived from body water. If the oxygen in water is labeled with 18O, then CO2 produced by respiration will contain labeled oxygen. In addition, as CO2 travels from the site of respiration through the cytoplasm of a cell, through the interstitial fluids, into the bloodstream and then to the lungs some of it is reversibly converted to bicarbonate. So, after consuming water labeled with 18O, the 18O equilibrates with the body's bicarbonate and dissolved carbon dioxide pool (through the action of the enzyme carbonic anhydrase). As carbon dioxide is exhaled, 18O is lost from the body. This was discovered by Lifson in 1949.〔Lifson, N., Gordon, G.B., Visscher, M.B. and Nier, A.O. (1949) The fate of utilized molecular oxygen and the source of the oxygen of respiratory carbon dioxide, studied with the aid of heavy oxygen. J. Biol. Chem. A , 180, 803–811.〕 However, 18O is also lost through body water loss (such as urine and evaporation of fluids). However, deuterium (the second label in the doubly labeled water) is lost ''only'' when body water is lost. Thus the loss of deuterium in body water over time can be used to mathematically compensate for the loss of 18O by the water-loss route. This leaves only the remaining net loss of 18O in carbon dioxide. This measurement of the amount of carbon dioxide lost is an excellent estimate for total carbon dioxide production. Once this is known, the total metabolic rate may be estimated from simplifying assumptions regarding the ratio of oxygen used in metabolism (and therefore heat generated), to carbon dioxide eliminated (see respiratory quotient). This quotient can be measured in other ways, and almost always has a value between 0.7 and 1.0, and for a mixed diet is usually about 0.8. In lay terms: * Metabolism can be calculated from oxygen-in/CO2-out. * DLW ('tagged') water is traceable hydrogen (deuterium), and traceable oxygen (18O). * The 18O leaves the body in two ways: (i) exhaled CO2, and (ii) water loss in (mostly) urine, sweat, & breath. * BUT: the deuterium leaves ''only'' in the second way (water loss). SO: from deuterium loss, we know how much of the tagged water left the body ''as'' water. And, since the concentration of 18O in the body's water is measured after the labeling dose is given, we ''also'' know how much of the tagged oxygen left the body in the water. (A simpler view is that the ratio of deuterium to 18O in body water is fixed, so total loss-rate of deuterium from the body multiplied by this ratio, immediately gives the loss rate of 18O in water.) Measurement of 18O dilution with time gives the total loss of this isotope by all routes (by water and respiration). Since the ratio of 18O to total water oxygen in the body is measured, we can convert 18O loss in respiration to total oxygen lost from the body's water pool via conversion to carbon dioxide. How much oxygen left the body ''as CO2'' is the same as the CO2 produced by metabolism, since the body only produces CO2 by this route. The CO2 loss tells us the energy produced, if we know or can estimate the respiratory quotient (ratio of CO2 produced to oxygen used). 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Doubly labeled water」の詳細全文を読む スポンサード リンク
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