Glossary of Selected Terms
The following glossary represents a list of various terms and definitions researchers may encounter while learning about isotopic tracers in metabolism.
Clearance is formally defined as the volume of biological fluid completely cleared of tracee per unit time. It is calculated as the ratio of Rd and the tracee concentration (e.g., mg/mL or umols/mL) in the pool (units: mL/kg/min or mL/min). It is an index of the tracee uptake normalized by tracee concentration. Note that the ratio of clearance and Vd is equal to k if you assume a single compartment.
k = Clearance
Dynamic steady state (DSS)
DSS exists when the mass of a substance in a defined system remains constant over time. In a steady state the rate of production or appearance (Ra) of a substance equals the rate of removal (Rd) of the substance.
Note: it is assumed that the volume of the pool and the dynamics of mixing in the pool in which that substance is dissolved remain constant.
The molar ratio of the tracer to the tracee generally used with stable isotopes. A general term that is used for tracer tracee ratio (TTR) or moles percent excess (MPE).
Fractional turnover rate (k)
k is the fraction of the tracee that is replaced per unit time assuming a single pool.
Half-life is the time it takes to replace one half of the original components of the pool.
k and t½ are related by the following equation:
F = e
Where F= fraction of the original tracee that remains at any time (t). F=½ at t½. If we solve for t½ in terms of k:
½ = e
ln(½)= ‑k t½
-ln(2)= ‑k t½
ln(2)/k = t½
Example: if k = 0.1/min, then t½ = 6.9 min
Are molecules that have the same chemical formula and arrangement of bonds and differ only in their isotopic composition. For example H2O, H2O (tritiated water) and H2O (i.e. heavy water) are isotopologues.
Are molecules of equal mass that have the same chemical formula and arrangement of bonds but have isotopes incorporated in the molecule.
For example, [3- H] glucose and [1- C] glucose both have a mass of 181.
[4,5- C2]glutamate is a different isotopomer than [1,2- C2]glutamate.
Mass Isotopomer Distribution (MID)
Is the fractional distribution of mass isotopomers in a molecule.
Because of natural abundance, a molecule such as glucose (C6H12O6) does not have a mass of 180. Some fraction of the glucose molecules will have a mass of 181 or more depending on the probability that one or more isotopes (e.g. C vs C) are in the molecule. This is represented as a distribution where M0 is denoted as a smallest possible mass (e.g. 180 in the case of glucose).
Note: the sum of the MID’s is =1
Moles percent excess (MPE)
The percent of the molecules that are tracer relative to tracee
MPE = Tracee * 100
The fractional abundance of isotopes of a chemical element as naturally found in biology.
O=0.99757 O=0.00038 O=0.00205
Note: sum for each element is equal to 1 for fractional abundance
Pool is the space in which the substance of interest is distributed (e.g. plasma). This space is assumed to be well-mixed.
Are molecules that have the same chemical formula and arrangement of bonds and isotopic composition but differ in where the isotopes are located in the molecule.
For example [3- H] glucose and [2- H] glucose
Specific activity (SA)
SA is the ratio of the amount of tracer to tracee in the pool.
For radioactive isotopes the units are usually expressed as dpm/mmol, dpm/g or cpm/g
Where dpm=disintegrations per min; cpm=counts per min
If stable isotopes are used, “enrichment” is defined as the molar ratio of tracer to tracee.
Tracee is the substance whose turnover is measured.
Tracer is the isotopically labeled (radioactive or stable isotope) form of the tracee.
Tracer-tracee ratio (TTR)
The molar ratio of the molecules that are tracer relative to tracee
TTR = Tracee
Turnover is the renewal rate of a “substance” in a defined system and is abbreviated Rt. This renewal can take place in two possible ways:
1. The substance can be synthesized and metabolized in the same tissue.
2. The substance can be synthesized at a site distant from its site of metabolism.
Note: the term turnover has an unequivocal meaning only when the substance is in a steady state. Units: mg/min, µmoles/min, mg/kg/min
Volume of distribution (Vd)
Vd is an empirically derived volume (i.e., pool) that the tracee rapidly mixes in. Vd is usually very close to the true pool size if the model which best describes the kinetics of the pool is one compartment (e.g., the extracellular space). Since the body usually cannot be considered a single compartment, the Vd is only an approximation of the pool size. The units are usually mL/kg.