Secondary R-and β-deuterium isotope effects for enolization reactions and equilibria have been determined by ab initio calculations, 1 H NMR spectroscopy, and triton exchange kinetics. Kinetic and equilibrium R-deuterium isotope effects for hydroxide ion-catalyzed enolization of acetaldehyde calculated by ab initio methods are normal and depend on the orientation of the secondary hydrogen with respect to the carbonyl group. The computed transition state structure indicates a small degree of bond rehybridization at the transition state. Experimentally measured secondary isotope effects on the deuteroxide ion-catalyzed proton exchange of acetophenone are k H /k D ) 1.08 ( 0.07 for R-CH 3 exchange and k H /k D ) 0.96 ( 0.08 for R-CH 2 D exchange. For R-CH 2 T exchange in water, the corresponding secondary isotope effect is k H /k D ) 1.06 ( 0.02, assuming the rule of the geometric mean is valid. These effects are smaller than the calculated equilibrium isotope effect for formation of the enolate ion-water complex: K H /K D ) 1.11-1.22 at the MP2 level. The normal kinetic isotope effects are smaller than might be expected due to a loss in hyperconjugation of the out-of-plane C-H bond and a lag in structural reorganization that contributes to the intrinsic barrier for proton transfer from carbon. Ionization of protonated acetone gives rise to an inverse secondary isotope effect of 0.97/D for the C-L bond adjacent to the carbonyl group and is consistent with a loss in hyperconjugation upon formation of the neutral ketone.
Secondary kH/kT kinetic isotope effects in H2O and kH/kT or kD/kT isotope effects in D2O have been measured for the triosephosphate isomerase-catalyzed conversion of dihydroxyacetone 3-phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The proton transfer steps are made rate-limiting using [1(R)-2H]-labeled substrate in D2O to slow the chemical steps, relative to product release. After a small correction for the beta-equilibrium isotope effect for dehydration of DHAP, the H/T kinetic isotope effect kH/kT = 1.27 +/- 0.03 for [1(R)-2H,(S)-3H]-labeled substrate in D2O is subtantially larger than the equilibrium isotope effect for enolization of DHAP, KH/KT = 1.12. The H/T isotope effect is related to the D/T isotope effect with a Swain-Schaad exponent y = 4.4 +/- 1.3. These results are consistent with coupled motion of the C-1 primary and secondary hydrogens of DHAP and tunneling. Large secondary kinetic isotope effects are a general feature of enzymatic enolization reactions while nonenzymatic enolization reactions show secondary kinetic isotope effects that are substantially smaller than equilibrium effects [Alston, W. A., II, Haley, K., Kanski, R., Murray, C.J., & Pranata, J. (1996) J. Am. Chem Soc., 118, 6562-6569]. Possible origins for these differences in transition state structure are discussed.
difficult, since it did not obviate the need for laparotomy. Of the 12 patients with jaundice on whom the test was carried out five had stones in the common bile duct, two had carcinoma of the hepatic duct, and five had carcinoma of the head of the pancreas. Cytological examination predicted the presence or absence of carcinoma with considerable accuracy.The triple test of Youngs et al. (1973) failed to diagnose carcinoma in one-third of the patients by the two intubation tests, and the abnormal pancreatic scans were not in themselves diagnostic of carcinoma. In the present study the additional information obtained from duodenography and cytology resulted in a correct diagnosis of carcinoma in all but one patient. A preoperative diagnosis of carcinoma of the pancreas allows suitable adjustment of preoperative preparation and also obviates the need for biopsy of a pancreatic mass, which may be misleading and dangerous. With increasing experience we hope that the accuracy of preoperative diagnosis will be improved further.We wish to thank the technical and nursing staff for their help
A determination was made of total urinary adenosine 3'-5'cyclic monophosphate (UcAMP), nephrogenous cyclic AMP (NcAMP) excretion and also of the renal tubular maximum reabsorptive capacity for phosphate T,P04/GFR (all expressed as a function of the glomerular filtrate) in fourteen patients with primary hypercalcaemic hyperparathyroidism and twelve control normal subjects. The hyperparathyroid patients gave a mean excretion of UcAMP (7.45f0.68 nmo1/100ml GF; mean+SEM), NcAMP(6~19+0~64nmo1/100ml GF) which were significantly greater (P <0.001) than those of normal controls,
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