Rate constants for decarboxylation reactions calculated using no barrier theory

No barrier theory (NBT) provides both a qualitative way of thinking about what makes a reaction fast or slow and a quantitative way of calculating the rate constant (free energy of activation) corresponding to a particular mechanism. The origin and development of this idea are reviewed and examples of its use for qualitative understanding are presented before applying it to a set of decarboxylations. From the literature, a set of best values for rate constants for decarboxylation was picked. Detailed mechanistic models were developed for reactions leading to delocalized “anions” or to localized anions. It was necessary to have pKa values for ionizaion of the carbon acids corresponding to all of these species and these were selected from the literature or estimated by linear free energy relations (or occasionally calculated from proton exchange data). Over the entire range of measured decarboxylation rate constants, a range of 1025 in rate constant, the calculated values were in good agreement with experiment, with two exceptions: malonate dianion, which has been reported but probably not measured, and glycine, where it is possible that a different mechanism is being followed, unfortunately, one which we do not yet know how to treat by NBT. NBT is both a qualitatively and quantitatively useful tool for understanding chemistry.

Glutamate metabolism in fetus and placenta of late-gestation sheep

Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.