Is there an energy conservation “system” in brain that protects against the consequences of energy depletion?

A poorly understood marked decrease (circa 50% of control) in local cerebral glucose utilization is caused by sublethal doses of NaCN. The decrease is global, occurring in essentially all brain regions and is entirely reversible within hours, leaving no obvious pathology. This event is not unique to NaCN in so far as a strikingly similar pattern of decreased glucose utilization occus with some other toxins. Nor can it be attributed to a direct action of NaCN since local application by microdialysis to the striatum produces a global depression. These results imply that some widely distributed system or substance is involved. We speculate the existence of a system possibly related to the reticular activating system that senses a fall in energy production and acts globally to make cells quiescent and thus would give some protection from excitotoxic driven damage.Special issue dedicated to Dr. Sidney Ochs.     

The Response to Exercise with Constant Energy Intake in Identical Twins

Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 ± 9.8 MJ (Mean ± SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p <0.001) and it was entirely accounted for by the loss of fat mass (p <0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p <0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomography (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm² (SEM = 5) to 52 cm² (SEM = 6) (p <0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p <0.05). Intrapair resemblance was observed for the changes in body weight (p <0.05), fat mass (P <0.01), percent fat (p <0.01), body energy content (p <0.01), sum of 10 skinfolds (p <0.01), abdominal visceral fat (p <0.01), fasting plasma triglycerides (p <0.05) and cholesterol (p <0.05), maximal oxygen uptake (p <0.05), and respiratory exchange ratio during submaximal work (p <0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during sub-maximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.     

Energy allocation for reproduction in a marsupial arboreal folivore,the common ringtail possum (Pseudocheirus peregrinus)

This study examines the annual energetics of a small folivorous marsupial, Pseudocheirus peregrinus. Particular attention was given to the energy and time allocated to reproduction by the females. Daily energy expenditure was measured directly using the doubly labelled water technique. Energy transferred to the young via the milk was estimated from information on milk composition and production. There was no significant seasonal variation in the energy expenditure or water influx of males or females. The mean daily energy expenditure of a 1-kg non-lactating adult ringtail possum was 615 kJ day^–1 or 2.2 times standard metabolic rate. Females showed significant changes in daily energy expenditure according to their reproductive status. Without the burden of lactation the total annual energy expenditure of an adult female was estimated as 212.4 MJ kg^–1 year^–1. The total annual energy expenditure of a female rearing two young was 247.5 MJ kg^–1 year^–1, with the late stage of lactation constituting the most energetically expensive period accounting for 30% of the total yearly energy expenditure during 24% of the time. Total metabolisable energy allocation during reproduction (22 MJ kg) was similar to estimates available for other herbivores, although, the peak metabolisable energy allocation during lactation (759 kJ day^–1) was lower than values available for other herbivores. The total energy requirement for reproduction (metabolisable energy plus potential energy exported to young via milk) suggests that the ringtail possum also has a relatively low overall energy investment in reproduction. It is suggested that the lactational strategy of the ringtail possum has been selected in order to spread the energy demands of reproduction over time due to constraints on the rate of energy intake imposed by a leaf diet and/or to prolong the mother-young bond. The strategies a female ringtail possum may employ to achieve energy balance when faced with the energy demands of reproduction are discussed.     

Comparison of carbohydrate utilization and energy charge in the yellow flag iris (Iris pseudacorus) and garden iris (Iris germanica) under anoxia

Carbohydrate and energy metabolism of the flooding- and anoxia-tolerant Iris pseudacorus and the intolerant Iris germanica rhizomes were investigated under experimental anoxic conditions. Rhizomes of I. pseudacorus and I. Germanica were incubated in the absence of oxygen from 0 to 60 and 16 days, respectively. Amounts of glucose, total reducing sugars and non-reducing sugars (starch, fructan and oligosaccharides) in the rhizomes were measured. Ethanol concentration and adenylate energy charge were determined enzymatically. Glucose content of I. pseudacorus rhizomes decreased gradually during the first 30 days under anoxia and then increased at the same time as adenylate energy charge values started to decline. In I. germanica rhizomes the changes were more dramatic and the time scale was much shorter than in I. pseudacorus but the changes were similar. Non-reducing sugar content of I. pseudacorus rhizomes decreased rapidly during the first 15 days under oxygen deprivation and then increased again, to near starting levels at 35 days. In I. germanica the amount of non-reducing sugars decreased gradually during the anoxic incubation. Under aerobic control conditions, adenylate energy charge (AEC) of I. pseudacorus and I. germanica rhizome tissue was 0.87±0.01 and 0.81±0.01, respectively. In I. pseudacorus AEC remained high until 30 days under anoxia. In contrast, the energy charge of I. germanica rhizome tissue remained above 0.6 for 4 days only. Large amounts of ethanol were found in anoxic rhizome tissues of I. pseudacorus (up to 0.21 M ) and I. germanica (0.06 M ) after 45 days and 8 days, respectively. The results are discussed in relation to flooding tolerance of these species.     

The generation of metabolic energy by solute transport

Secondary metabolic-energy-generating systems generate a proton motive force (pmf) or a sodium ion motive force (smf) by a process that involves the action of secondary transporters. The (electro)chemical gradient of the solute(s) is converted into the electrochemical gradient of protons or sodium ions. The most straightforward systems are the excretion systems by which a metabolic end product is excreted out of the cell in symport with protons or sodium ions (energy recycling). Similarly, solutes that were accumulated and stored in the cell under conditions of abundant energy supply may be excreted again in symport with protons when conditions become worse (energy storage). In fermentative bacteria, a proton motive force is generated by fermentation of weak acids, such as malate and citrate. The two components of the pmf, the membrane potential and the pH gradient, are generated in separate steps. The weak acid is taken up by a secondary transporter either in exchange with a fermentation product (precursor/product exchange) or by a uniporter mechanism. In both cases, net negative charge is translocated into the cell, thereby generating a membrane potential. Decarboxylation reactions in the metabolic breakdown of the weak acid consume cytoplasmic protons, thereby generating a pH gradient across the membrane. In this review, several examples of these different types of secondary metabolic energy generation will be discussed.     

Conversion of a racemate into a single enantiomer in one step by chiral liquid chromatography: Studies with rac-2,2′-diiodobiphenyl

The enantiomers of rac-2,2′-diiodobiphenyl were separated by liquid chromatography on microcrystalline triacetylcellulose. The conformational lability, a large separation factor α, and a suitable capacity factor k′(+) of this biphenyl allowed us to convert the racemate into 90% of enantiomerically pure (-)-2,2′-diiodobiphenyl and 10% of pure (+)-2,2′-diiodobiphenyl, respectively, by a series of in situ racemization-elution cycles. The much better retained (+)-enantiomer was racemized on the chromatographic column at 50°C after the less retained (-)-enantiomer has already been eluted at 8°C. © 1995 Wiley-Liss, Inc.     

Model of synchronized population bursts in electrically coupled interneurons containing active dendritic conductances

We constructed a computer model of 128 interneurons, each with multiple dendritic branches and an axonal segment. The model neurons were interconnected by gap junctions between dendritic compartments, as are known to occur in rat and guinea-pig hilar interneurons. The model contained no excitatory synapses. In the presence of low-frequency spontaneous action potentials, the model generated synchronized population bursts, when gap junction resistance was 50 M and there were at least two gap junctions per neuron on average. Population bursts occurred only when the dendrites of model neurons were electrically excitable. Consistent with experiment, somatic hyperpolarization during the population burst uncovered partial spikes. In the model, partial spikes originated in electrically active dendrites driven by coupled dendrites. This model may account for population bursts in hilar interneurons that occur in 4-aminopyridine (4AP) together with blockers of GABA_A and excitatory amino acid (EAA) receptors.     

Steady-state kinetics of the overall oxidative phosphorylation reaction in heart mitochondria. Determination of the coupling relationships between the respiratory reactions and miscellaneous observations concerning rate-limiting steps

The linear sequence of steps involved in the oxidation of extramitochondrial succinate by O₂ in bovine heart mitochondria was examined by a steady-state kinetic method to determine whether or not freely diffusible intermediates occur between the various inhibitor-sensitive steps. The kinetic method is based on the facts (1) that if two inhibitor-sensitive steps within a sequence are linked by a freely diffusible intermediate, inhibition of one will make the other less rate limiting in the overall reaction and thus will increase the amount of inhibitor of the other step required for half-maximal inhibition of the overall reaction, and (2) that if the two steps are not linked in this manner, inhibition of one will make the other more rate limiting and thus will decrease the amount of inhibitor of the other required for half-maximal inhibition. These two types of coupling relationships between steps were designated as sequential and fixed, respectively. The results indicate the existence of freely diffusible intermediates (sequential coupling relationships) between the succinate transport and succinate dehydrogenase reactions, between the succinate dehydrogenase and cytochromebc ₁ reactions, and between the cytochromesbc ₁ andaa ₃ reactions. Uncoupling respiration from phosphorylation results in the coupling relationship between thebc ₁ andaa ₃ reactions becoming partially fixed. This change is accompanied by marked decreases in the degrees to which thebc ₁ andaa ₃ reactions limit the overall reaction and appears to account for the large uncoupler-induced releases of inhibition at the levels of thebc ₁ andaa ₃ reactions observed previously by others. It is suggested that cytochromec is the freely diffusible intermediate between thebc ₁ andaa ₃ reactions and that the uncoupler-induced changes occur as a result of formation of functional and highly efficient supercomplexes between cytochromec and the cytochromesbc ₁ andaa ₃ complexes.     

Incorporation of [14C]cinnamate into hydrolase-resistant components of the primary cell wall of spinach

[¹⁴C]Cinnamate was taken up very rapidly by cultured spinach cells and completely incorporated into low-MW conjugates within 20 min. The ¹⁴C-labelled products were similar whether the [¹⁴C]cinnamate was supplied continuously over a period of hours via a peristaltic pump or instantaneously. Radioactivity was slowly recruited from the low-MW pool into aromatic components of the cell-wall fraction. Saponification of the radioactive wall fraction yielded, in addition to radioactive ferulate and p-coumarate, large amounts of ethyl acetate-soluble radioactive material with the properties of oxidatively coupled phenols. The coupled material was associated with the most highly ‘Driselase’-resistant fractions of the cell wall. In contrast, ‘Driselase’ released most of the wall's ferulate and p-coumarate on disaccharide fragments. It is suggested that the oxidatively coupled phenols are formed from simpler phenols by peroxidase and that they cross-link the polysaccharides to which they are attached, making these polysaccharides relatively ‘Driselase’-resistant.