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Biomedical subjects

A J Hulbert

Publications and source records attributed to A J Hulbert.

At least 19 recordsLinked to original sources

Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile.

Standard metabolic rate is 7-fold greater in the rat (a typical mammal) than in the bearded dragon, Amphibolurus vitticeps (a reptile with the same body mass and temperature). Rat hepatocytes respire 4-fold faster than do hepatocytes from the lizard. The inner membrane of isolated rat liver mitochondrial has a proton permeability that is 4-5-fold greater than the proton permeability of the lizard liver mitochondrial membrane per mg of mitochondrial protein. The greater permeability of rat mitochondria is not caused by differences in the surface area of the mitochondrial inner membrane, but differences in the fatty acid composition of the mitochondrial phospholipids may be involved in the permeability differences. Greater proton permeability of the mitochondrial inner membrane may contribute to the greater standard metabolic rate of mammals.

Adenosine Triphosphate

Development of mammalian endothermic metabolism: quantitative changes in tissue mitochondria.

The development of energy metabolism of mammalian tissues was assessed in the tammar wallaby Macropus eugenii by the measurement of mitochondrial parameters in the liver, heart, kidney, and brain. Tissues taken from wallabies (n = 27) ranging from 10-day-old pouch young (weighing approximately 4 g) to adults (averaging 6.2 kg) were weighed and fixed, and mitochondrial volume and mitochondrial membrane surface area (MMSA) were determined by quantitative electron microscopy techniques. Developmental changes in these parameters were analyzed chronologically and allometrically. Relative growth rates of all four tissues decreased during development. Liver and heart showed constant allometric growth throughout development, whereas kidney and brain showed biphasic allometric growth. Tissue metabolic intensity assessed by MMSA (m2/cm3 tissue) was constant in liver, showed a threefold increase in brain during pouch life, showed a fourfold increase in the heart between 100 and 200 days of age, and showed a twofold increase in the kidney at the end of pouch life. In all tissues, adult levels of tissue metabolic capacity were present at pouch exit. In all four tissues, total MMSAs were at "reptilian" levels at birth and gradually increased to "mammalian" levels. Each tissue exhibited a different developmental timetable. When the total MMSAs for all four tissues were summed there was a similar pattern of allometric development between summed MMSA and whole animal metabolic rate.

Aging

Membrane fatty acid changes during the cell cycle of CV-1 cells.

Monolayers of CV-1 cells were synchronized at the G1/S boundary of the cell cycle by a 24-h 2 mM thymidine blockade. Uptake of tritiated thymidine indicated that the peak DNA synthesis occurred 6-8 h after release from the block and that cell cycle time was 18-20 h. The fatty acid composition of phospholipids extracted from cells at 0, 7, and 18 h postblockade was measured by gas chromatography. The results indicate cyclic changes in membrane fatty acids with a significant increase in long-chain polyunsaturated fatty acids during the DNA synthesis phase (S phase) of the cell cycle.

Animals

Thyroid hormones during development of a marsupial, the tammar wallaby, Macropus eugenii.

The levels of thyroid hormones in the plasma and the activities of 5'-deiodinase activity in liver and kidney were determined in the tammar wallaby, Macropus eugenii, from early pouch life to adulthood. The total concentration of plasma thyroxine (T4) was below 15 nmol/l before day 75 of pouch life, rose to about 75 nmol/l at day 160, and then decreased to about 12 nmol/l in the adult. The total concentration of plasma tri-iodothyronine (T3) was below 0.4 nmol/l before day 120, increased to 3 nmol/l by about day 220 and then decreased to 1.0 nmol/l in adults. Concentrations of free T4 and free T3 followed a similar pattern but peaked at 45 and 160 pmol/l respectively. Concentrations of reverse T3 (rT3) were extremely variable, ranging from 0 to 1 nmol/l at day 100, and from 0 to greater than 2 nmol/l at day 180. After about day 230, rT3 levels fell rapidly and were below 0.3 nmol/l in adults. Liver and kidney 5'-deiodinase activities, which were undetectable before day 80, reached adult levels by day 220. Half-maximal activity of both these enzymes occurred at about day 205, mid-way between the peaks of T4 and T3. These findings suggest that the systems supporting synthesis and release of hormones from the thyroid gland are probably mature by about day 160 of pouch life in the tammar, while peripheral deiodinase activity, which is a major factor in the production of T3 in the plasma, matures by about day 220. These events thus precede the development of physiological independence of the young tammar from its mother.

Animals

Evolution of mammalian endothermic metabolism: mitochondrial activity and cell composition.

Body composition was measured and compared in Amphibolurus vitticeps and Rattus norvegicus (a reptile and a mammal with the same weight and body temperature). Homogenates were prepared from liver, kidney, brain, heart, lung, and skeletal (gastrocnemius) muscle, and mitochondria were isolated. Cytochrome oxidase activities of both tissue homogenates and isolated mitochondria were measured (at 37 degrees C) as was protein content. Phospholipids were extracted from liver and kidney, and the fatty acid composition was determined. The brain, liver, kidney, heart, and skeletal muscle were significantly larger in the mammal, whereas the skin, reproductive organs, lung, and digestive tract showed no significant difference in size. All mammalian tissues examined contained approximately 50% more protein and phospholipid than the respective reptilian tissue. Although the mammalian phospholipids contained significantly less total unsaturated fatty acids, these unsaturated fatty acids were significantly more polyunsaturated than in the reptilian tissues. Tissue cytochrome oxidase activity was significantly greater in mammals when expressed on a wet weight basis but not when expressed on a tissue protein basis. Mitochondrial cytochrome oxidase activity (on a protein basis) was the same in both species in liver, kidney, and brain, but in heart, lung, and skeletal muscle mammalian mitochondria were twice as active as reptilian mitochondria. The implications of these differences in tissue composition were discussed relative to the evolution of mammalian endothermy.

Animals

Thyroid function in a lizard, a tortoise and a crocodile, compared with mammals.

1. Thyroid activity was examined in the lizard, Trachydosaurus rugosus, the tortoise Chelodina longicollis and the crocodile, Crocodylus johnstoni, acclimated to 20-22 degrees C and 30-32 degrees C. Thyroidal uptake and release of 125I, plasma concentrations of T3 and T4 were measured as was resting oxygen consumption (at 30 degrees C) before and after both thyroidectomy and thyroxine injections. 2. All three species showed 125I uptake at both temperatures and showed no thyroidal release of 125I at 20-22 degrees C but exhibited thyroidal release of 125I (and presumably hormone secretion) at 30-32 degrees C. 3. Plasma concentrations of thyroxine ranged from 0.55 nM to 3.24 nM and triiodothyronine from 0.14 nM to 0.51 nM. 4. Neither thyroidectomy nor thyroxine injections had any effect on metabolic rate in 20-22 degrees C acclimated lizards. Thyroidectomy resulted in a significant decrease in metabolic rate in 30-32 degrees C acclimated lizards and tortoises and thyroxine injections resulted in significant increases in metabolism in 30-32 degrees C acclimated lizards, tortoises and crocodiles. 5. A comparison of thyroid parameters in reptiles and mammals concluded that although the reptilian thyroid is active at high temperatures it is still considerably less active than it is in mammals.

Alligators and Crocodiles

Effects of endurance training and captivity on activity metabolism of lizards.

Two groups of Amphibolurus nuchalis, an Australian agamid lizard, were maintained in captivity for 8 wk. The "trained" group was given submaximal exercise at 1 km/h on a motorized treadmill, 30 min/day, 5 days/wk; the treadmill was inclined 10% for the last 5 wk. The "sedentary" group was not exercised. Endurance capacity did not change significantly in either group, but sprint speed decreased in trained lizards. The sedentary group exhibited significant decreases in maximal O2 consumption, standard metabolic rate, and heart mass, but an increase in liver mass. Trained lizards exhibited significant decreases in heart and thigh muscle masses, but significant increases in liver mass, hematocrit, liver pyruvate kinase, and heart citrate synthase activities. It is concluded that the adaptive response to endurance training, typical of mammals, does not generally occur in lizards. Moreover, levels of chronic activity that would elicit adaptive responses in mammals may be excessive for lizards and may induce pathological effects in joints and skeletal muscle. The ecological and evolutionary significance of these conclusions is discussed.

Analysis of Variance

Evolution of mammalian endothermic metabolism: "leaky" membranes as a source of heat.

O2 consumption was measured at 37 degrees C in tissue slices of liver, kidney, and brain from Amphibolurus vitticeps and Rattus norvegicus (a reptile and mammal with same weight and body temperature) both in the presence and absence of ouabain. O2 consumption of the mammalian tissues was two to four times that of the reptilian tissues and the mammalian tissues used three to six times the energy for Na+-K+ transport than the reptilian tissues. Passive permeability to 42K+ was measured at 37 degrees C in liver and kidney slices, and passive permeability to 22Na+ was measured at 37 degrees C in isolated and cultured liver cells from each species. The mammalian cell membrane was severalfold "leakier" to both these ions than was the reptilian cell membrane, and thus the membrane pumps must use more energy to maintain the transmembrane ion gradients. It is postulated that this is a general difference between the cells of ectotherms and endotherms and thus partly explains the much higher levels of metabolism found in endothermic mammals.

Animals

An allometric comparison of the mitochondria of mammalian and reptilian tissues: the implications for the evolution of endothermy.

The effects of body size and phylogeny on metabolic capacities were examined by comparing the mitochondrial capacities of 6 mammalian and 4 reptilian species representing 100-fold body weight ranges. The mammals examined included 3 eutherian, 2 marsupial and a monotreme species and the reptiles 2 saurian, 1 crocodilian and 1 testudine species. The tissues examined were liver, kidney, brain, heart, lung and skeletal muscle. Allometric equations were derived for tissue weights, mitochondrial volume densities, internal mitochondrial membrane surface area densities, tissue mitochondrial membrane surface areas both per gram and per total tissue and summated tissue mitochondrial membrane surface areas. For the mammals and reptiles studied a 100% increase in body size resulted in average increases of 68% in internal organ size and 107% in skeletal muscle mass. Similarly, total organ mitochondrial membrane surface areas increase in mammals and reptiles by an average 54% and for skeletal muscle by an average 96%. These values are similar to increases in standard (54 and 71%) and maximum (73 and 77%) organismal metabolism values found by other authors for mammals and reptiles respectively. Although the allometric exponents (or rates of change with increasing body size) of the mitochondrial parameters in mammals and reptiles are statistically the same, in general the total amount of mitochondrial membrane surface area in the mammalian tissues are four times greater than found in the reptilian tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Alligators and Crocodiles

Minimal metabolism, summit metabolism and plasma thyroxine in rodents from different environments.

Rodents were live-trapped in three environments (desert, intermediate and coastal) in Southern California, USA, chosen because of the taxonomic overlap of species. Upon capture, blood samples were taken and plasma thyroxine concentrations were measured. Four species (Dipodomys merriami, Perognathus fallax, Peromyscus eremicus and Peromyscus californicus) were returned to the laboratory for measurement of minimal and summit rates of metabolism. Heteromyid rodents had significantly lower plasma thyroxine concentrations (14-44 nmol l-1) than cricetid rodents (18-93 nmol l-1). Although there was significant habitat difference in plasma thyroxine levels, this influence was not constant between heteromyid and cricetid rodents. In most species, the desert individuals had the lowest plasma thyroxine concentration. Minimal metabolic rates were lower than expected in all four species, as well as in the tropical heteromyid Liomys salvini and summit metabolic rates were similarly reduced in all species. Upon capture there was considerable variation in plasma thyroxine concentration of different species (23-93 nmol l-1). However, following 10 weeks in captivity, the range and variability of plasma thyroxine levels in these species was considerably reduced (32-64 nmol l-1).

Animals

Mammals: an allometric study of metabolism at tissue and mitochondrial level.

Body composition, mitochondrial volume density, and mitochondrial membrane surface area were measured in six species of mammals representing a 100-fold weight range (18-2,067 g). The mammals examined included three eutherian species, two marsupial, and one monotreme species. The tissues examined were liver, kidney, brain, lung, heart, and skeletal muscle (gastrocnemius). Allometric equations were derived for tissue weight, and the allometric exponents ranged from 0.69 (brain) to 1.01 (skeletal muscle). Allometric relationships for mitochondrial membrane surface area were also determined both per milliliter tissue and per total tissue. Small mammals had a higher mitochondrial membrane surface area per milliliter tissue than large mammals in all tissues examined. These differences were significant in liver, kidney, brain, and heart. Total mitochondrial membrane surface area per tissue had allometric exponents ranging from 0.55 (kidney) to 0.78 (skeletal muscle). When total mitochondrial membrane surface area was summated for the major internal organs examined (liver, kidney, heart, and brain), the allometric equation was mitochondrial membrane surface area (m2) = 3.04 body wt0.59 (g). This was similar to the exponent of standard metabolic rate against body weight in the species examined (i.e., 0.62). The inclusion of skeletal muscle and lung into the summated mitochondrial membrane surface area increased the exponent to 0.76. This is compared with the relationship between maximal O2 consumption and body size in mammals.

Animals

A comparative study of the metabolic capacity of hearts from reptiles and mammals.

The metabolic capacities of reptilian and mammalian hearts have been investigated using two methods: measurement of mitochondrial enzyme activity (cytochrome oxidase) and measurement of both mitochondrial volume density and membrane surface area. The heart tissues from the reptiles and mammals showed 2-fold "weight specific" and 3-fold total organ metabolic capacity differences. Heart mitochondria from reptiles and mammals showed 2-fold differences in the activity of their enzymes per mg of mitochondrial protein yet showed very similar mitochondrial surface areas per cm3 of mitochondria. Heart mitochondria differ from liver mitochondria which have the same enzyme activities per mg of protein and the same mitochondrial surface area per cm3 of mitochondria in both the reptiles and mammals. A wide variety of reptiles and mammals both showed relationships between total heart metabolic capacity and body weight. Mammals have larger hearts than similar sized reptiles and their hearts have a greater proportion of cellular volume occupied by mitochondria.

Animals

Comparison of the "mammal machine" and the "reptile machine": energy production.

Standard metabolism and body composition were measured in Amphibolurus nuchalis and Mus musculus (a reptile and mammal with the same weight and body temperature). The metabolic capacity for energy production was assessed in liver, heart, brain, and kidney in the lizard and mouse by two methods: measurement of mitochondrial enzyme activity (cytochrome oxidase) and measurement of both mitochondrial volume density and membrane surface area. Both methods gave a three- to sixfold greater capacity for energy production in the mammal compared to the lizard which is less than the eightfold difference in their standard metabolisms. The difference in energy production capacity was not due to any single parameter but was a summation of several smaller differences. The mammal had relatively larger internal organs than the reptile, their organs had a greater proportion of mitochondria, and their mitochondria had a greater relative membrane surface area. These differences, it is suggested, may be due in part to different thyroid function in reptiles and mammals.

Animals

Seasonal changes in membrane lipid transitions and thyroid function in the hedgehog.

Upper (Tf) and lower (Ts) temperature limits of order-disorder transitions in blood cell lipids of hedgehogs, Erinaceus europaeus, were determined over an annual cycle. There was a significant decrease in the temperature of both Tf and Ts from values of 19 and 6 degrees C, respectively, for summer animals to values of 14 and -2.0 degrees C for winter animals. Plasma thyroxine levels decreased from a summer mean of 16.0 nmol/liter to a mean of 2.3 nmol/liter in winter. Basal oxygen consumption also decreased from the summer mean 0.45 ml/g body wt/h to a mean 0.39 ml/g body wt/h in winter. In winter a group of hedgehogs kept indoors at room temperature was compared with a group kept outdoors exposed to natural winter conditions, and there was no significant difference between them in the above parameters. We conclude that the winter membrane lipid and metabolic changes are not a response to low temperature per se but part of a circannual homeostatic adjustment at least partly regulated by thyroid hormone.

Animals

Thyroid function in a hibernator, Spermophilus tridecemlineatus.

Thyroid hormone secretion (assessed as thyroid 125I release rate) was monitored in Spermophilus tridecemlineatus from summer to winter (July-December) in 1973. The average release rate in July was 2.3% per day, but in August this rate decreased significantly and remained at an average 0.52% per day until December. This low rate (being similar to that of hypophysectomized rats), and the absence of any change in oxygen consumption following thyroidectomy, suggested hormone secretion was "turned off" during this period. During the period August-December, four S. tridecemlineatus showed normal thermoregulatory responses to anterior hypothalamic cooling but no thyroidal response whether restrained, unrestrained, or anesthetized. Thyroid 125I uptake (and presumably hormone manufacture) continued during the period August-December and 24-h uptake averaged 27.0% in December. Possible reasons for "turning off" thyroid hormone secretion are discussed, and it is concluded this is to allow the membrane fatty acids to revert to a less-saturated condition in preparation for low body temperatures during hibernation.

Animals