Effect of training/detraining on submaximal exercise responses in humans

Human subjects participated in a training/detraining paradigm which consisted of 7 wk of intense endurance training followed by 3 wk of inactivity. In previously sedentary subjects, training produced a 23.9 +/- 7.2% increase in maximal aerobic power (V02max) (group S). Detraining did not affect group S V02max. In previously trained subjects (group T), the training/detraining paradigm did not affect V02max. In group S, training produced an increase in vastus lateralis muscle citrate synthase (CS) activities (nmol.mg protein-1. min-1) from 67.1 +/- 14.5 to 106.9 +/- 22.0. Detraining produced a decrease in CS activity to 80 +/- 14.6. In group T, pretraining CS activity (139.5 +/- 14.9) did not change in response to training. Detraining, however, produced a decrease in CS activity (121.5 +/- 7.8 to 66.8 +/- 5.9). Group S respiratory exchange ratios obtained during submaximal exercise at 60% V02max (R60) decreased in response to training (1.00 +/- 0.02 to 0.87 +/- 0.02) and increased (0.96 +/- 0.02) after detraining. Group T R60 (0.91 +/- 0.01) was not affected by training but increased (0.89 +/- 0.02 to 0.95 +/- 0.02) after detraining. R60 was correlated to changes in CS activity but was unrelated to changes in V02max. These data support the hypothesis that the mitochondrial content of working skeletal muscle is an important determinant of substrate utilization during submaximal exercise.     

Maximal oxygen consumption in relation to subordinate traits in lines of house mice selectively bred for high voluntary wheel running.

We studied relations between maximal O2 consumption (VO2 max) during forced exercise and subordinate traits associated with blood O2 transport and cellular respiration in four lines of mice selectively bred for high voluntary wheel running (S lines) and their four nonselected control (C) lines. Previously, we reported VO2 max of 59 females at three Po2 (hypoxia = 14% O2, normoxia = 21%, hyperoxia = 30%). Here, we test the hypothesis that variation in VO2 max can be explained, in part, by hemoglobin concentration and Po2 necessary to obtain 50% O2 saturation of Hb (an estimate of Hb affinity for O2) of the blood as well as citrate synthase activity and myoglobin concentration of ventricles and gastrocnemius muscle. Statistical analyses controlled for body mass, compared S and C lines, and also considered effects of the mini-muscle phenotype (present only in S lines and resulting from a Mendelian recessive allele), which reduces hindlimb muscle mass while increasing muscle mass-specific aerobic capacity. Although S lines had higher VO2 max than C, subordinate traits showed no statistical differences when the presence of the mini-muscle phenotype was controlled. However, subordinate traits did account for some of the individual variation in VO2 max. Ventricle size was a positive predictor of VO2 max at all three Po2. Blood Hb concentration was a positive predictor of VO2 max in S lines but a negative predictor in C lines, indicating that the physiological underpinnings of VO2 max have been altered by selective breeding. Mice with the mini-muscle phenotype had enlarged ventricles, with higher mass-specific citrate synthase activity and myoglobin concentration, which may account for their higher VO2 max in hypoxia.     

Respiratory sinus arrhythmia alteration following training in endurance athletes.

Significant increases in maximum oxygen consumption (VO2max) were noted in nine young track athletes following an 8-week high-intensity running period (P less than 0.05). VO2max was measured, prior to and following the training program, using an on-line, open-circuit spirometry system. Parasympathetic activity was assessed using heart period variation (R-R interval in milliseconds) during carefully controlled breathing activity (R sinus arrhythmia). Following the training program, a 7.3% increase in aerobic capacity was associated with a 23.1% augmentation of efferent parasympathetic activity (P less than 0.01). These data suggest that enhanced aerobic capacity increases efferent parasympathetic tone.     

Divergent selection for aerobic capacity in rats as a model for complex disease

Based upon ideas about evolution, we put forth the argumentthat the capacity to transfer energy via aerobic metabolismis such a central feature of mammalian biology, that it mustalso be the primary determinant of complex disease. From this,we hypothesized that artificial selection on low and high capacityfor aerobic exercise would create lines that can be used todefine the divide between health and disease. In 1996 we beganlarge-scale divergent selection for aerobic treadmill runningcapacity in a widely heterogeneous stock of rats (N:NIH). Byten generations we developed lines of low capacity runners (LCR)and high capacity runners (HCR) that on average differed by317%. As a correlated trait, body mass increased at each generationin the LCR while the body mass decreased in the HCR. The linesalso separated for key factors of systemic oxygen transportcapacity such as maximal oxygen consumption (VO₂max), tissueperfusion, capillary density, and oxidative enzyme activity(citrate synthase and B-HAD). We also tested our hypothesisthat differences in aerobic energy transfer would produce ratsthat contrast for risk factors associated with complex disease.Indeed, the lines separated for cardiovascular risk factorsincluding differences in blood pressure, cardiac contractility,visceral adiposity, plasma free fatty acids, and triglycerides.The decrease in aerobic capacity was also associated with lowamounts of several proteins required for mitochondrial function.     

The effect of elevated levels of thyroxine on the aerobic capacity of locomotor muscles of the tufted duck,Aythya fuligula

Following extended periods of relative inactivity, or prior to migration, birds are able to increase the aerobic capacity of their locomotory muscles. Thyroid hormones may influence this process. A preliminary study was undertaken to assess the ability of elevated levels of thyroxine to increase the aerobic capacity of the locomotory and cardiac muscles of adult tufted ducks. Administration of thyroxine in the food for 8 weeks had little effect on body mass or on the masses of the pectoralis, semitendinosus and iliofibularis muscles, although there were increases in resting oxygen consumption and in the mass of the cardiac ventricles. The maximum activity of the aerobic enzyme, citrate synthase, was significantly greater in the left ventricle, liver, and iliofibularis muscles (P<0.005) of treated birds. However, while there was clearly no difference in activity in the semimembranosus leg muscle, that of the pectoralis was not quite significant (P=0.078). It is concluded that addition of supra-physiological levels of exogenous thyroxine may induce a differential increase in the maximum activity of citrate synthase in the locomotor muscles of the tufted duck, which is correlated with the fibre type composition of these muscles. These results are consistent with those found in studies on rats, with slow oxidative fibres being the most sensitive, and fast glycolytic fibres the least sensitive, to thyroxine treatment.Abbreviations BM body mass - CS citrate synthase - CYTOX cytochrome c oxidase - FG last glycolytic - FOG fast oxydative glycolytic - VO₂ oxygen consumption - SO slow oxidative - T₄ thyroxine - T₃ triiodothyronine     

Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria

The aim of the present study was to examine whether parameters of isolated mitochondria could account for the in vivo maximum oxygen uptake (VO2max) of human skeletal muscle. VO2max and work performance of the quadriceps muscle of six volunteers were measured in the knee extensor model (range 10-18 mmol O2 x min(-1) x kg(-1) at work rates of 22-32 W/kg). Mitochondria were isolated from the same muscle at rest. Strong correlations were obtained between VO2max and a number of mitochondrial parameters (mitochondrial protein, cytochrome aa3, citrate synthase, and respiratory activities). The activities of citrate synthase, succinate dehydrogenase, and pyruvate dehydrogenase, measured in isolated mitochondria, corresponded to, respectively, 15, 3, and 1.1 times the rates calculated from VO2max. The respiratory chain activity also appeared sufficient. Fully coupled in vitro respiration, which is limited by the rate of ATP synthesis, could account for, at most, 60% of the VO2max. This might be due to systematic errors or to loose coupling of the mitochondrial respiration under intense exercise.     

Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease

Muscle mitochondrial content is tightly regulated, and requires the expression of both nuclear and mitochondrial genes. In addition, muscle mitochondrial content is a major determinant of aerobic exercise capacity in healthy subjects. The current study was designed to test the hypothesis that in healthy humans, muscle mitochondrial DNA (mtDNA) content is correlated with citrate synthase activity (a representative nuclear-encoded mitochondrial enzyme) and aerobic exercise capacity as defined by whole-body peak oxygen consumption (VO2). Furthermore, it was postulated that these relationships might be altered with disease. Twelve healthy and five paraplegic subjects underwent exercise testing and vastus lateralis muscle biopsy sampling. An additional ten healthy subjects and eight patients with unilateral peripheral arterial disease (PAD) underwent exercise testing and gastrocnemius muscle biopsy sampling. Citrate synthase activity and mtDNA content were positively correlated in the vastus lateralis muscles from the healthy subjects. This relationship was similar in muscle from paraplegic subjects. mtDNA content was positively correlated with peak VO2 in the healthy subjects and in the paraplegic subjects in whom peak VO2 had been elicited by functional electrical stimulation of the muscle. In contrast, the PAD subjects demonstrated higher mtDNA contents than would have been predicted based on their claudication-limited peak VO2. Thus, in healthy humans there are strong relationships between muscle mtDNA content and both muscle citrate synthase activity and peak VO2. These relationships are consistent with coordinant nuclear DNA and mtDNA expression, and with mitochondrial content being a determinant of aerobic exercise capacity. The relationships seen in healthy humans are quantitatively similar in paraplegic patients, but not in patients with PAD, a disease which is associated with a metabolic myopathy. The relationships between mtDNA content, mitochondrial enzyme activities and exercise capacity provide insight into the physiologic and pathophysiologic regulation of muscle mitochondrial expression.     

Strength training and determinants of VO2max in older men

The effects of strength training on maximal aerobic power (VO2max) and some of its determinants were studied in 12 healthy older men (60-72 yr). They underwent 12 wk of strength conditioning of extensors and flexors of each knee with eight repetitions per set, three sets per session, and three sessions per week at 80% of the one repetition maximum (1 RM). Left knee extensors showed a 107% increase in 1 RM, a 10% increase in isokinetic strength at 60 degrees/s, and a 23% increase in total work performed during 25 contractions on an isokinetic dynamometer. Strength measurements of the untrained left elbow extensors showed no change. Leg cycle ergometer VO2max per unit fat-free mass increased by an average 1.9 ml (P = 0.034) whereas arm cycle VO2max was unchanged. Pulmonary function, hemoglobin concentration, erythrocyte volume, plasma volume, and total blood volume did not change. Biopsies of the vastus lateralis showed a 28% increase in mean fiber area, no change in fiber type distribution, a 15% increase in capillaries per fiber, and a 38% increase in citrate synthase activity. The data suggest that the small increase in leg cycle VO2max in older men may be due to adaptations in oxidative capacity and increased mass of the strength-trained muscles.     

A discordance in rosiglitazone mediated insulin sensitization and skeletal muscle mitochondrial content/activity in Type 2 diabetes mellitus

Skeletal muscle mitochondrial dysfunction is hypothesized to contribute to the pathophysiology of insulin resistance and Type 2 diabetes. Whether thiazolidinedione therapy enhances skeletal muscle mitochondrial function as a component of its insulin-sensitizing effect is unknown. To test this, we evaluated skeletal muscle mitochondria and exercise capacity in Type 2 diabetic subjects with otherwise normal cardiopulmonary function in response to rosiglitazone therapy. Twenty-three subjects were treated for 12 wk and underwent pre- and posttherapy metabolic stress testing and skeletal muscle biopsies. Rosiglitazone significantly ameliorated fasting glucose, insulin, and free fatty acid levels but did not augment the subjects' maximal oxygen consumption (Vo(2max)) or their skeletal muscle mitochondrial copy number. The baseline Vo(2max) correlated strongly with muscle mitochondrial copy number (r = 0.56, P = 0.018, n = 17) and inversely with the duration of diabetes (r = -0.67, P = 0.004, n = 23). Despite the global lack of effect of rosiglitazone-mediated insulin sensitization on skeletal muscle mitochondria, subjects with the most preserved functional capacity demonstrated some plasticity in their mitochondria biology as evidenced by an upregulation of electron transfer chain proteins and in citrate synthase activity. This study demonstrates that the augmentation of skeletal muscle mitochondrial electron transfer chain content and/or bioenergetics is not a prerequisite for rosiglitazone-mediated improved insulin sensitivity. Moreover, in diabetic subjects, Vo(2max) reflects the duration of diabetes and skeletal muscle mitochondrial content. It remains to be determined whether longer-term insulin sensitization therapy with rosiglitazone will augment skeletal muscle mitochondrial bioenergetics in those diabetic subjects with relatively preserved basal aerobic capacity.     

The effect of endurance-training on the maximum activities of hexokinase, 6-phosphofructokinase,citrate synthase,and oxoglutarate dehydrogenase in red and white muscles of the rat

Adult female rats were subjected to an eleven-week endurance-training programme, and, for the first time, the maximum activities of enzymes that can indicate the quantitative capacities of both anaerobic glycolysis and the Krebs cycle in muscle (viz. 6-phosphofructokinase and oxoglutarate dehydrogenase respectively) were measured in heart plus white and fast-oxidative skeletal muscle. No changes were observed in heart muscle. In fast-oxidative skeletal muscle, activities of hexokinase, citrate synthase, and oxoglutarate dehydrogenase were increased by 51, 26, and 33% respectively but there was no effect on 6-phosphofructokinase. These results demonstrate that in red muscle there is no effect of this training programme on the anaerobic capacity but that of the aerobic system is increased by one third. In white skeletal muscle, only the activity of citrate synthase was increased, which indicates that this activity may not provide even qualitative information about changes in capacity of the Krebs cycle.     

Maximal oxygen consumption test during arm exercise--reliability and validity.

The reliability and validity of a continuous progressive arm test, in which maximal 02 consumption (V02 max arm) is determined, were analyzed. Forty-one men (28.2 +/- 8.8 yr) performed the test twice. Eighteen additional men (22.6 +/- 5.6 yr) performed the arm test, as well as the treadmill run, in which maximal O2 consumption VO2max leg) was determined. The validity of the VO2 max arm test was computed, using VO2 max leg as a criterion for the individual's aerobic capacity. The reliability coefficients of VO2 max arm, VEmax arm, and HRmax arm were 0.94, 0.98, and 0.76, respectively, indicating a high reliability of the testmthe validity coefficient of VO2max arm was only 0.74. The regression equation of VO2max leg on VO2max arm was y = 24.4 + 0.9 +/- 4.4 (Syx). These findings indicate that, following the suggested protocol, the individual repeatedly uses the same muscles and does reach an all-out stage. However, different individuals apparently are aided by their trunk and leg muscles to different degrees, which lowers the validity of this test as a predictor of aerobic capacity.     

Developmental,genetic, and environmental components of aerobic capacity at high altitude

The aerobic capacity of 268 subjects (158 males and 110 females) was evaluated in La Paz, Bolivia situated at 3,750 m. The sample included 1) 39 high altitude rural natives (all male); 2) 67 high altitude urban natives (32 male, 35 female); 3) 69 Bolivians of foreign ancestry acclimatized to high altitude since birth (37 male, 32 female); 4) 50 Bolivians of foreign ancestry acclimatized to high altitude during growth (25 male, 25 female); and 5) 43 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (25 male, 18 female). Data analyses indicate that 1) high altitude urban natives, acclimatized to high altitude since birth or during growth, attained higher aerobic capacity than subjects acclimatized to high altitude during adulthood; 2) age at arrival to high altitude is inversely related to maximum oxygen consumption (V?O² max) expressed in terms L/min or ml/min/kg of lean body mass, but not in terms of ml/min/kg of body weight; 3) among subjects acclimatized to high altitude during growth, approximately 25% of the variability in aerobic capacity can be explained by developmental factors; 4) as inferred from evaluations of skin color reflectance and sibling similarities, approximately 20 to 25% of the variability in aerobic capacity at high altitude can be explained by genetic factors; 5) except among the non-Bolivians acclimatized to high altitude during adulthood, the aerobic capacity of individuals with high occupational activity level is equal to the aerobic capacity of high altitude rural natives; and 6) the relationship between occupational activity level and aerobic capacity is much greater among subjects acclimatized to high altitude before the age of 10 years than afterwards. Together these data suggest that the attainment of normal aerobic capacity at high altitude is related to both developmental acclimatization and genetic factors but its expression is highly mediated by environmental factors, such as occupational activity level and body composition. © 1995 Wiley-Liss, Inc.     

Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP:citrate lyase by phosphorylated sugars

Recombinantly expressed human ATP:citrate lyase was purified from E. coli, and its kinetic behavior was characterized before and after phosphorylation. Cyclic AMP-dependent protein kinase catalyzed the incorporation of only 1 mol of phosphate per mole of enzyme homotetramer, and glycogen synthase kinase-3 incorporated an additional 2 mol of phosphate into the phosphorylated protein. Isoelectric focusing revealed that all of the phosphates were incorporated into only one of the four enzyme subunits. Phosphorylation resulted in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal, displaying negative cooperativity, to hyperbolic. The phosphorylated recombinant enzyme is more similar to the enzyme isolated from mammalian tissues than unphosphorylated enzyme with respect to the K(m) for citrate, CoA, and ATP, and the specific activity. Fructose 6-phosphate was found to be a potent activator (60-fold) of the unphosphorylated recombinant enzyme, with half-maximal activation at 0.16 mM, which results in a decrease in the apparent K(m) for citrate and ATP, as well as an increase in the V(max) of the reaction. Thus, human ATP:citrate lyase activity is regulated in vitro allosterically by phosphorylated sugars as well as covalently by phosphorylation.     

Additive effects of training and high-fat diet on energy metabolism during exercise

This study was conducted to obtain additional information about the adaptations after 12 wk of high-fat diet (HFD) per se or HFD combined with endurance training in the rat using a two [diet: carbohydrate (CHO) or HFD] by two (training: sedentary or trained) by two (condition at death: rested or exercised) factorial design. Adaptation to prolonged HFD increases maximal O2 uptake (VO2max; 13%, P less than 0.05) and submaximal running endurance (+64%, P less than 0.05). This enhancement in exercise capacity could be attributed to 1) an increase in skeletal muscle aerobic enzyme activities (3-hydroxyacyl-CoA dehydrogenase and citrate synthase in soleus and red quadriceps) or 2) a decrease in liver glycogen breakdown in response to 1 h exercise at 80% VO2max. When training is superimposed to HFD, the most prominent finding provided by this study is that the diet-induced effects are cumulative with the well-known training effect on VO2max, exercise endurance, oxidative capacity of red muscle, and metabolic responses to exercise, with a further reduction in liver glycogen breakdown.     

A program of moderate physical training for Wistar rats based on maximal oxygen consumption

Moderate physical training is often associated with improved cardiorespiratory fitness in athletes and the general population. In animals, studies are designed to investigate basic physiology that could be invasive and uncomfortable for humans. The standardization of an exercise training protocol for rats based on maximal consumption of oxygen (VO(2)max) is needed. This study validated a program of moderate physical training for Wistar rats based on VO(2)max determined once a week. A 10-stage treadmill running test was developed to measure VO(2)max through an indirect, open circuit calorimeter. Thirty male Wistar rats (210-226 g) were randomly assigned to either a nontrained group or a trained group. The animals were evaluated weekly to follow their VO(2)max during 8 weeks of moderate training and to adjust the intensity of the protocol of training. The soleus muscle was removed for determination of citrate synthase activity. Trained animals maintained their values of VO(2)max during a moderate running training and showed a significant less body weight gain. An increase of 42% in citrate synthase activity of the soleus muscle from trained rats was found after the training program. Our study presents a protocol of moderate physical training for Wistar rats based on VO(2)max. Peripheral adaptations such as the values of citrate synthase activity also responded to the moderate training program imposed as observed for VO(2)max. Other studies can use our protocol of moderate training to study the physiologic adaptations underlying this specific intensity of training. It will provide support for study with humans.     

The influence of muscle metabolic characteristics on physical performance

This study describes the influence of muscle fiber type composition, enzyme activities and capillary supply on muscle strength, local muscle endurance or aerobic power and capacity. Muscle biopsies were obtained from m. vastus lateralis in thirteen physically active men. Histochemical staining procedures were applied to assess the percentage of fast twitch (FT) fibers, muscle fiber area, and capillary density. Also, the activity of citrate synthase (CS), creatine kinase (CK), hexokinase (HK), lactate dehydrogenase (LDH), and phosphofructokinase (PFK) were analysed using fluorometrical assays. Peak torque at 'low' and 'high' angular velocities was measured during leg extension. Similarly, muscle fatigue (e.g. peak torque decline) and recovery from a short-term exercise task were measured during maximal, voluntary consecutive leg extensions. Aerobic power (VO2max) and aerobic capacity (e.g. onset of blood lactate concentration; OBLA), as defined by a blood lactate concentration of 4 mol X 1(-1) were measured during cycling. Peak torque at a high angular velocity was positively correlated with % FT area (p less than 0.001). Fatigue and recovery were correlated with LDH X CS-1 (p less than 0.001). WOBLA was best correlated with PFK and PFK X CS-1 (p less than 0.001). Hence, muscle strength was partly determined by fiber type composition whereas local muscle endurance, recovery and aerobic capacity reflect mainly capillary supply and the activity of key enzymes involved in aerobic and anaerobic metabolism.     

Uniqueness of interval and continuous training at the same maintained exercise intensity.

The present study sought to evaluate the inconsistencies previously observed regarding the predominance of continuous or interval training for improving fitness. The experimental design initially equated and subsequently maintained the same relative exercise intensity by both groups throughout the program. Twelve subjects were equally divided into continuous (CT, exercise at 50% maximal work) or interval (IT, 30 s work, 30 s rest at 100% maximal work) training groups that cycled 30 min day-1, 3 days.week-1, for 8 weeks. Following training, aerobic power (VO2max), exercising work rates, and peak power output were all higher (9-16%) after IT than after CT (5-7%). Vastus lateralis muscle citrate synthase activity increased 25% after CT but not after IT. A consistent increase in adenylate kinase activity (25%) was observed only after IT. During continuous cycling testing the CT group had reduced blood lactate (lab) levels and respiratory quotient at both the same absolute and relative (70% VO2max) work rates after training, while the IT group displayed similar changes only at the same absolute work rates. By contrast, both groups responded similarly during intermittent cycling testing with lower lab concentrations seen only at absolute work rates. These results show that, of the two types of training programs currently employed, IT produces higher increases in VO2max and in maximal exercise capacity. Nevertheless, CT is more effective at increasing muscle oxidative capacity and delaying the accumulation of lab during continuous exercise.     

Invited Review: Dynamic exercise performance in Masters athletes: insight into the effects of primary human aging on physiological functional capacity.

Physiological functional capacity (PFC) is defined here as the ability to perform the physical tasks of daily life and the ease with which these tasks can be performed. For the past decade, we have sought to determine the effect of primary (healthy) adult human aging on PFC and the potential modulatory influences of gender and habitual aerobic exercise status on this process by studying young adult and Masters athletes. An initial approach to determining the effects of aging on PFC involved investigating changes in peak exercise performance with age in highly trained and competitive athletes. PFC, as assessed by running and swimming performance, decreased only modestly until age 60-70 yr but declined exponentially thereafter. A progressive reduction in maximal O2 consumption (V(O2 max)) appears to be the primary physiological mechanism associated with declines in endurance running performance with advancing age, along with a reduction in the exercise velocity at lactate threshold. Because V(O2 max) is important in mediating age-related reductions in exercise performance and PFC, we then investigated the modulatory influence of habitual aerobic exercise status on the rate of decline in V(O2 max) with age. Surprisingly, as a group, endurance-trained adults appear to undergo greater absolute rates of decline in V(O2 max) with advancing age compared with healthy sedentary adults. This appears to be mediated by a baseline effect (higher V(O2 max) as young adults) and/or a marked age-related decline in exercise training volume and intensity (stimulus) in endurance-trained adults. Thus the ability to maintain habitual physical activity levels with advancing age appears to be a critical determinant of changes in PFC in part via modulation of maximal aerobic capacity.     

The effect of valine substitution for glycine in the dimer interface of citrate synthase from Thermoplasma acidophilum on stability and activity

To determine the role of hydrophobic interactions in the dimer interface of citrate synthase (CS) from Thermoplasma (Tp) acidophilum in thermostabilization, we have used site-directed mutagenesis to replace Gly 196 by Val on the helix L of the subunit interface. Recombinant wild-type and Gly 196 mutant TpCS enzymes were largely identical in terms of substrate specificities (K(m) for oxaloacetate and acetyl CoA). However, the mutation not only reduced catalytic activity (about 10-fold) (i.e., V(max), k(cat) and specific activity) of the TpCS, but also decreased its thermal and chemical stability. Archaeal citrate synthase is active as a dimer, since residues from both monomers participate in the active site. Our results suggest that Gly196 --> Val mutation interferes with dimerization, so that improper dimerization or dissociation of the dimer would have a profound affect on the activity as well as the conformational stability of TpCS.     

Intermittent locomotion increases endurance in a gecko

Nocturnal geckos can actively forage at low temperatures. A low minimum cost of locomotion allows greater sustainable speeds by partially offsetting the decrease in maximal oxygen consumption (VO2max) associated with low nocturnal temperatures. The nocturnality hypothesis (Autumn et al. 1997) proposes that the reduced cost of continuous locomotion is a shared, derived characteristic that increases the capacity to sustain locomotion at low temperatures. Yet many lizards move intermittently at speeds exceeding those that elicit VO2max. We exercised the frog-eyed gecko, Teratoscincus przewalskii, continuously and intermittently on a treadmill. At an exercise speed of 0.90 km h-1 (270% maximum aerobic speed), lizards alternating a 15-s exercise period with a 30-s pause period exhibited a 1.7-fold increase in distance capacity (total distance traveled before fatigue) compared with lizards exercised continuously at the same average speed (0.30 km h-1). The average aerobic cost of intermittent exercise was not significantly different from VO2max. Locomoting intermittently could augment the increase in endurance resulting from the low minimum cost of continuous locomotion in nocturnal geckos. Intermittent behavior could increase the endurance of lizard movement in general.