Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.
Both V-type nerve agents
MeP(O)(OR)(SCH2CH2NR‘2),
VX (R = C2H5; R‘ =
i-C3H7) and its
isomeric
analog RVX (the “Russian V-agent”, R =
i-C4H9; R‘ =
C2H5), react slowly but completely with
an
equimolar amount of H2O via exclusive P−S cleavage to
produce the corresponding phosphonic
acid (MeP(O)(OR)OH) and 2-aminoethanethiol
(HSCH2CH2NR‘2). The
reaction is believed to be
initiated by nucleophilic attack of the deprotonated phosphonic acid on
the protonated V-agent to
produce a diphosphonate intermediate
((MeP(O)(OR))2O) that rapidly hydrolyzes to
regenerate the
phosphonic acid. The autocatalytic ionic chain reaction is thus
continued in the nearly nonaqueous
reaction medium. The viscous final product mixture remains
reactive toward freshly added trace
amounts of the V-agent, giving the same final reaction half-life of
13−15 h at 23 °C. When water
is insufficient and depleted, the diphosphonate intermediate
accumulates and reacts with the
aminoethanethiol to regenerate the V-agent. This autocatalytic
hydrolysis process is not observed
with a simpler phosphonothioate analog
(MeP(O)(OC2H5)(SC2H5)),
which suggests that the attack
of the phosphonic acid on the V-agent is intramolecularly assisted by
the protonated amino group.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.