Human hypoxanthine-guanine phosphoribosyltransferase

A mutant form of human hypoxanthine-guanine phosphoribosyltransferase (HPRTToronto) was isolated from erythrocytes of a male patient with gout due to a partial deficiency of enzyme activity. The tryptic peptides of HPRTToronto were mapped by reverse-phase high pressure liquid chromatography in an attempt to define the precise abnormality in its primary structure. Sequence analysis of the single aberrant peptide in HPRTToronto revealed an arginine to glycine amino acid substitution at position 50. A single nucleotide change in the codon for arginine 50 (CGA leads to GGA) could explain this substitution.     

Effect of prostaglandins on lipid transfer between high- and low-density lipoproteins in human plasma

Prostaglandin (PG) E1 was shown to stimulate the transfer of phosphatidylcholine and cholesterol esters from human high density lipoproteins to low density lipoproteins. The enhancement of the interlipoprotein lipid transfer by PGE1 was observed both at low prostaglandin concentrations under conditions of spontaneous exchange as well as in the presence of the lipoprotein-depleted plasma and the partly purified lipid transfer plasma protein. At the same time PGE2 showed no significant influence on the interlipoprotein lipid transfer. It is supposed that the effect of PGE1 is due to the PGE1-induced reorganization of the high density lipoprotein surface and that the PG-lipoprotein interaction is a factor which regulates cholesterol homeostasis.     

Functional anatomy of the musculature of the trachea.

The smooth musculature of the human trachea was studied and compared with earlier observations in the rabbit. The results may be summarized as follows: 1. The annular m. constrictor tracheae, previously observed in the rabbit, has also been identified in the human trachea. 2. Longitudinal muscle fibers outside the constrictor musculature were observed in man. These fibers are rudimentary and appear to be of no functional importance. 3. From a functional point of view, it appears justified to regard the outer tracheal musculature largely as a constrictor musculature. 4. The main function of the outer musculature of the trachea and the elastic cartilaginous arches is to maintain the stability of the tracheal wall. 5. The variation of the lumen of the trachea is mainly controlled by the m. trachealis in the pars membranacea.     

Kinetics and mechanism of acetohydroxy acid synthase isozyme III from Escherichia coli

Acetohydroxy acid synthase (AHAS, EC 4.1.3.18) isozyme III from Escherichia coli has been studied in steady-state kinetic experiments in which the rates of formation of acetolactate (AL) and acetohydroxybutyrate (AHB) have been determined simultaneously. The ratio between the rates of production of the two alternative products and the concentrations of the substrates pyruvate and 2-ketobutyrate (2KB) leading to them, R, VAHB/VAL = R[( 2KB]/[pyruvate]), was found to be 40 +/- 3 under a wide variety of conditions. Because pyruvate is a common substrate in the reactions leading to both products and competes with 2-ketobutyrate to determine whether AL or AHB is formed, steady-state kinetic studies are unusually informative for this enzyme. At a given pyruvate concentration, the sum of the rates of formation of AL and AHB was nearly independent of the 2-ketobutyrate concentration. On the basis of these results, a mechanism is proposed for the enzyme that involves irreversible and rate-determining reaction of pyruvate, at a site which accepts 2-ketobutyrate poorly, if at all, to form an intermediate common to all the reactions. In the second phase of the reaction, various 2-keto acids can compete for this intermediate to form the respective acetohydroxy acids. 2-Keto acids other than the natural substrates pyruvate and 2-ketobutyrate may also compete, to a greater or lesser extent, in the second phase of the reaction to yield alternative products, e.g., 2-ketovalerate is preferred by about 2.5-fold over pyruvate. However, the presence of an additional keto acid does not affect the relative specificity of the enzyme for pyruvate and 2-ketobutyrate; this further supports the proposed mechanism. The substrate specificity in the second phase is an intrinsic property of the enzyme, unaffected by pH or feedback inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relations between anxiolytic effects of diazepam and changes in the EEG spectral power

The influence of diazepam (1; 5; 10 mg/kg, i. p.), chlorpromazine (1 mg/kg) and amphetamine (1; 5 mg/kg) on the Fourier's spectral EEG power of sensomotor cortex and dorsal hippocampus and conflict behavior freely moving albino and cotton (Sigmondon hispidus) rats was studied. Effects of diazepam (5 mg/kg) in cotton rats were similar, but influence on the theta-activity was more expressed. Correlation between slowing of theta-activity and extent of anxiolytic effect in conflict situation was showed. On the basis of the results obtained the authors discuss possible mutual relations between the influence of diazepam on EEG and anxiolytic effect of benzodiazepines.