Alternative Pathways of Glucose Utilization in Brain; Changes in the Pattern of Glucose Utilization in Brain Resulting from Treatment of Rats with 6-Aminonicotinamide

The effect of 6-aminonicotinamide (6AN) treatment on the activities of alternative pathways of glucose metabolism in 20-day-old rat brain was evaluated by measurements of yields of 14CO2 from glucose labeled with 14C on carbons 1, 2, 3 + 4, or 6 and uniformly labeled glucose, and from the incorporation of 14C from specifically labeled glucose into lipids by brain slices from cerebral hemispheres and cerebellum. At the highest dose of 6AN used (35 mg/kg body weight) there was a significant decrease in the 14CO2 yields via the pentose phosphate pathway, the glycolytic route, tricarboxylic acid (TCA) cycle, and via the glutamate-gamma-aminobutyric acid pathway. Giving a graded series of doses (20-35 mg 6AN/kg body weight) revealed a hierarchy of responses in which the pentose phosphate pathway, lactate, glyceride-glycerol, and fatty acid formation were most sensitive, followed, in sequence, by the pyruvate dehydrogenase reaction, the glutamate-gamma-aminobutyrate route and, finally, the TCA cycle. The nature of the blocks in the various pathways was examined by the use of metabolite profiles.     

PROLIFERATION KINETICS OF THE MOUSE BLADDER AFTER IRRADIATION

The proliferative response of the mouse bladder was investigated, using continuous labelling with tritiated thymidine, at various times after a single dose of radiation. Bladder epithelial and vascular endothelial cells were studied. The cell turnover rate in unirradiated epithelium and endothelium was found to be extremely slow (in excess of 1 year). Irradiation with a single dose of 25 Gy resulted in compensatory proliferation of the epithelium but the response was not initiated for many months. At 3 months after irradiation there was little difference from the control proliferation rate, but from 6 to 22 months after irradiation (the end of the study) there was a period of sustained rapid proliferation with the cell turnover time reduced to approximately 1 week. The increase in proliferative activity observed at 22 months was found to be dose—dependent. Endothelial cells in the blood vessels of the submucosa also showed an increased turnover rate after irradiation and the timing of this reponse was found to be similar to that of the epithelium. The onset of compensatory proliferation in both cell types was found to coincide with marked histological and functional changes in the bladder. In this slowly proliferating tissue, the onset of rapid compensatory proliferation after irradiation is delayed and occurs at the time that functional impairment is observed. This supports the postulate that proliferation is unlikely to contribute much to the sparing effect of prolonged fractionated radiotherapy in slowly dividing tissues.     

Effect of experimental diabetes on glycolytic intermediates and regulation of phosphofructokinase in rat lens

The pattern of glycolytic intermediates in the lens of alloxan-diabetic rats was indicative of regulation at phosphofructokinase. The changes in metabolites influencing phosphofructokinase activity in the diabetic, relative to the normal, rat lens were: glucose 6-phosphate, 182%; fructose 6-phosphate, 107%; fructose diphosphate, 57%. There was also a marked decrease in phosphoenolpyruvate, pyruvate, lactate and ATP but no significant change in other triose phosphates or cyclic AMP. The resuts are considered in relation to the early changes in [Ca²⁺] known to occur in lens in diabetes and to the coordinating effect of fructose diphosphate on flux through the glycolytic route.     

The form and function of cnidarian spirocysts

Summary The electron-dense capsule tip (apical cap) of sea anemone and coral spirocysts is of a different structure than the capsule wall. The capsule wall is composed of a double layer of fiber-like materials which cross each other at roughly right angles. The innermost layer is characterized by numerous serrations, the tips of which project into the lumen of the capsule. Within each serration, a band of finely cross-striated material encircles the capsule at right angles to its longitudinal axis. The membrane lining the lumen of the capsule appears to be continuous with the wall of the undischarged thread. The outer capsule wall layer consists of closely spaced microfilaments (cnidofilaments) which are oriented in the longitudinal axis of the capsule. The cnidofilaments appear to merge with the apical cap material. Contrary to some previous reports in the literature, it has been found that spirocysts normally discharge by eversion, as do nematocysts. The relationship of the capsule wall sub-structure to the spirocyst discharge process is discussed.Thanks are due Dr. Cadet Hand for the use of the facilities of the Bodega Marine Laboratory of the University of California and B. Miller, F. Doroshow, C. Bigger, G. Chapman and E. Chang for expert technical assistance. The use of the facilities of the Electron Microscope Laboratory and Electronics Research Laboratory of the University of California at Berkeley and the Eelectron Microscope Laboratory of the Florida State University is gratefully acknowledged. Part of this work was made possible by NSF Grant GB-40547 to the senior author     

Properties of the low-temperature Photosystem I primary reaction in the P-700-chlorophyll a-protein

The Photosystem I primary reaction, as measured by electron paramagnetic resonance changes of P-700 and a bound iron-sulfur center, has been studied at 15°K in P-700-chlorophyll a-protein complexes isolated from a blue-green alga. One complex, prepared with sodium dodecyl sulfate shows P-700 photooxidation only at 300°K, whereas a second complex, prepared with Triton X-100, is photochemically active at 15°K as well as at 300°K. Analysis of these two preparations shows that the absence of low-temperature photoactivity in the sodium dodecyl sulfate complex reflects a lack of bound iron-sulfur centers in this preparation and supports the assignment of an iron-sulfur center as the primary electron acceptor of Photosystem I.     

The presence of aromatic L-amino acid decarboxylase in certain intestinal nerve cells

Summary The presence of aromatic 1-amino acid decarboxylase (AADC) in nerve cell bodies of the intrinsic plexuses of the guinea-pig small intestine was demonstrated by incubating segments of intestine with 1-dopa in the presence of an inhibitor of monoamine oxidase, pargyline. After such incubation, some nerve cell bodies gave a fluorescence histochemical reaction indicative of the presence of a decarboxylated product of 1-dopa, probably dopamine. No fluorescence reaction occurred in the unincubated control or if the inhibitor of AADC, RO 4-4602, was included in the incubation mixture. The AADC-containing cell bodies apparently do not take up and store dopamine, because no fluorescence could be detected after incubation with dopamine and a monoamine oxidase inhibitor. The AADC-containing cells were found in about half of the ganglia of the submucous plexus of the guinea-pig small intestine, but were considerably less frequent in the myenteric plexus. They were also found in the other areas examined in this study, that is, in both enteric plexuses of the guinea-pig distal colon and of the small intestines of rabbits and rats.     

The modifying effect of manganese on the enzymic profiles and pathways of carbohydrate metabolism in rat liver and adipose tissue during development

The effect of Mn²⁺ on the pattern of emergence of enzymes in rat liver and adipose tissue was studied in weaned rats given a milk diet (high fat) or sucrose-casein diet (high carbohydrate) for three weeks. Addition of Mn²⁺ to the high fat diet was associated with induction of key glycolytic, lipogenic and pentose pathway enzymes in both liver and adipose tissue; parallel increases were found in the incorporation of [1-¹⁴C] glucose into lipid and CO₂. Mn²⁺ induced a change in the profile of enzyme activity similar in pattern to that found in rats given a high sucrose diet or that produced by insulin treatment. Mn²⁺ appears partially to overcome the regulatory feed-back mechanisms of the high fat diet and to provide a signal for the coordinated increase of glucose catabolic and lipogenic processes.     

AXONAL TRANSPORT OF LABELLED PROTEINS IN SENSORY FIBRES OF RABBIT VAGUS NERVE IN VITRO

—Rabbit vagus nerves and nodose ganglia were incubated in vitro for up to 24 h in two-compartment chambers. After the introduction of [³H]leucine or [³H]fucose to the ganglion compartments a rapid anterograde axonal transport of labelled proteins or glycoproteins occurred at rates of 330 ± 44 mm/day and 336 ± 30 mm/day respectively. Accumulation of [³H]leucine-labelled proteins proximal to a ligature on the nerve was unaffected by a delay of up to 6 h between removal of the nerve and labelling in vitro. Accumulation was prevented by inhibition of protein synthesis in the ganglion but not in the axon and was inhibited in a graded manner by colchicine.