Studies on the Mutual Influences of Substrates on Mammalian Alpha-Keto Acid Metabolism

The branched-chain amino acids leucine, isoleucine and valine are transaminated to their respective a-keto acid analogues; a-keto- isocaproate (KIC) a-keto-p-methyIvalerate (KMV) and a-ketoiso- valerate (KIV) in normal mammalian tissues. Recently an interest in the genetic anomaly branched-chain ketoaciduria or maple syrup urine disease , a metabolic disease involving the oxidative decarboxylation of the three branched-chain CC-keto acids, has stimulated efforts to characterize the nature of the enzymic conversions leading from the a-keto acids to their acyl coenzyme A products. These studies have been extended toward a consideration of the metabolic interrelationships among these a-keto acids (KIC, KMV, KIV). Furthermore, the effects of the branched-chain a-keto acids upon the metabolism of pyruvate and of a-ketoglutarate have been investigated. In addition, there has been an attempt to determine whether, in the normal and the abnormal (branched-chain ketoaciduric) animal, such interrelationships might constitute a significant physiological regulatory mechanism. a-Keto acid dehydrogenase activities were estimated by the Ik quantitative measurement of CO^ evolved from carboxyl-labeled a- keto acid substrates. The a-keto acid dehydrogenase enzyme activities were measured in several fractions of bovine liver homogenates prepared by differential centrifugation techniques. Subcellular distribution studies established that the branched- :hain a-keto acid dehydrogenase activities were localized principally „n the mitochondri ., and more specifically on the outside of the inner membrane of the mitochondria. In addition to the particulate activity, minor amounts of dehydrogenase activity with KMV and KIC /ere noted in the soluble (not sedimented at 80,000 x £ for one lour) fraction. The particulate branched-chain a-keto acid dehydrogenase activities were shown to depend upon added nicotinamide adenine linucleotide (NAD+) and coenzyme A for maximal activity. Also jbserved were apparent requirements fox calcium, magnesium and Inorganic phosphate. These findings lend support to the assumption :hat the branched-chain a-keto acids are catabolized by a mechanism analogous to that known to exist for the well-characterized ayruvate and a-ketoglutarate dehydrogenase complexes. The apparent Michaelis constant for each of these keto acids KIC, KMV, KIV, pyruvate, a-ketoglutarate) was determined. In general, the values for the branched-chain a-keto acids are of the . -h \u3erder of 4 x 10 M, while those for pyruvate and a-ketoglutarate -ij. -I4. ire slightly lower, 0.8 x 10 M and 2 x 10 M respectively. The degree and type of influence exerted among the various a- :eto acids was examined directly by following the enzymatic lip .iberation of CO^ from carboxyl-labeled substrate in the presence if an alternate unlabeled a-keto acid. A mutually inhibitory iattern among KIC, KIV and KMV was noted. In addition, each of the •ranched-chain keto acids exerted a marked inhibition of pyruvate dehydrogenase and a-ketoglutarate dehydrogenase activities. Inhibitions were of the competitive type in all instances except for a-ketoglutarate dehydrogenase activity, where a mixed type of inhibition was seen. The apparent inhibitor constants were in a range such that a significant mutual influence among the branched- chain a-keto acids could exist in vi ^o. Also, the inhibitory effects of KIC upon pyruvate dehydro \u27.anase could be considered to be significant at normal cellular concentrations of these metabolite The net effect of the inhibitory action of the branched-chain a-keto acids on each other and upon pyruvate dehydrogenase in the normal animal is likely a homestatic balance, which allows for catabolism of excess branched-chain amino acids, while concurrently influencing the flow of pyruvate to acetyl coenzyme A. The abnormal situation, as obtained in branched-chain keto aciduria, results in extremely elevated levels of all three branched chain a-keto acids. As these acids accumulate proximal to the metabolic block at the level of oxidative decarboxylation, they may nearly completely restrict the activity of pyruvate dehydrogenase, and exert substantial inhibitory effects at a-ketoglutarate dehydrogenase. These effects could severely limit the production of energy via the Krebs tricarboxylic acid cycle. In addition, production of acyl coenzyme A intermediates necessary for fatty acid synthesis would be affected. Thus, as the result of a genetic.lesion, which is manifest in the inability of the animal to catabolize the branched-chain a-keto acids, these intermediates accumulate, and in turn may exert a deleterius influence upon cellular energy requirements, as well as on production of essential metabolic intermediates. These effects in the abnormal situation could account for many of the symptoms observed in branched-chain ketoaciduria

Optimization of Low Reynolds Number Airfoils for Martian Rotor Applications Using an Evolutionary Algorithm

The Mars Helicopter (MH) will be flying on the NASA Mars 2020 rover mission scheduled to launch in July of 2020. Research is being performed at the Jet Propulsion Laboratory (JPL) and NASA Ames Research Center to extend the current capabilities and develop the Mars Science Helicopter (MSH) as the next possible step for Martian rotorcraft. The low atmospheric density and the relatively small-scale rotors result in very low chord-based Reynolds number flows over the rotor airfoils. The low Reynolds number regime results in rapid performance degradation for conventional airfoils due to laminar separation without reattachment. Unconventional airfoil shapes with sharp leading edges are explored and optimized for aerodynamic performance at representative Reynolds-Mach combinations for a concept rotor. Sharp leading edges initiate immediate flow separation, and the occurrence of large-scale vortex shedding is found to contribute to the relative performance increase of the optimized airfoils, compared to conventional airfoil shapes. The oscillations are shown to occur independent from laminar-turbulent transition and therefore result in sustainable performance at lower Reynolds numbers. Comparisons are presented to conventional airfoil shapes and peak lift-to-drag ratio increases between 17% and 41% are observed for similar section lift

The New Economics of Livestock Production Management

The importance of heterogeneity of animal attributes in livestock production is assessed. Preliminary results indicate that variance and skew measures of attributes may be becoming more important over time.livestock economics, herd management, livestock marketing, Livestock Production/Industries, Marketing,

Survey of Diseases in Wild Turkeys in Arkansas

Nineteen dead wild turkeys were necropsied and 573 live wild turkeys were physically examined for pathological agents in Arkansas between 1992 and 1997 to determine the proximate role disease may play in declining wild populations in Arkansas. Necropsy of the dead wild turkeys identified avian pox and histomoniasis as the most common diseases (16% and 11% of necropsies, respectively). Avian pox was recorded from three major physiographic regions in the state (Ozark Highlands, Ouachita Mountains, Gulf Coastal Plain). One hen died of non-accidental crop impaction, the fifth occurrence observed in the southeastern United States. Another hen died after developing severe, focal necrotic dermatitis caused by a Penicillium sp. fungus, the first occurrence observed in wild turkeys. All live wild turkeys appeared free of gross signs of disease. We found diseases in wild turkeys in Arkansas are not uncommon and are more diverse than previously reported. Continued monitoring of disease in wild turkeys is therefore encouraged

No Difference found in Hamstring Strength across Division I Football Positions

Hamstring injuries are one of the most common injuries sustained in professional football with 800+ hamstring injuries per year. These hamstring injuries often occur between late swing (eccentric contraction) and early ground contact. PURPOSE: To investigate the correlation of eccentric hamstring strength to muscle volume across positional groups. METHODS: Athletes were divided into three homogeneous groups based on position (big (e.g., linemen), skill (e.g., receivers), combo (e.g., linebackers)). Seventy-three NCAA Division I football players participated (24 big, 37 skill, and 12 combo). Hamstring strength was collected for each leg while performing 3 Nordic curls on a Nordbord device. The peak force of each leg was summed for our data analysis. Collective hamstring volume for each athlete was found through MRI. RESULTS: A Pearson’s product correlation demonstrated an overall moderate correlation (r = 0.52, p \u3c 0.0001) between hamstring muscle volume and strength, with skill players demonstrating a strong correlation (r = 0.66, p \u3c 0.0001), combo players demonstrating a moderate correlation (r = 0.49, p \u3c 0.0001), and big players demonstrating a weak correlation (r = 0.39, p \u3c 0.0001). An ANOVA showed no statistically significant difference of hamstring strength between positional groups (p = 0.1074) relative to hamstring volume (p \u3c 0.0001). CONCLUSION: The observed overall moderate correlation between hamstring strength and muscle volume across positional groups indicates that factors outside of muscle volume contribute to muscle strength. Our data also suggests that, regardless of position, hamstring muscle strength was similar when accounting for volume. Muscle volume was the best predictor of strength for the skill group. However, other factors should be considered, such as motor control factors. In the combo and big groups, these additional factors play a larger role

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted