Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 13 rabbits the rectus femoris muscle was freely transplanted from the left to the right side using microneurovascular anastomoses. About 7 months after surgery the muscle transplants were assessed functionally by force measurements. On the average, the transplanted muscles regained 55 percent of the maximal tetanic tension of unoperated, normal rectus femoris muscles, expressed as force per gram of muscle weight even 68 percent. After functional assessment, the muscles were weighed and then used for histologic, histochemical, planimetric, and biochemical evaluation. H&E-stained cross sections showed a high content of healthy muscle fibers; only some small atrophic and single fat cells were scattered over the cross sections. Good reinnervation over the sutured muscle nerve was confirmed by the type-grouping of muscle fibers in the NADH and myofibrillar ATPase staining. There was an excellent correlation between the functional results and the histologic picture as well as the content of choline acetyltransferase (CAT). A certain parallelism was found between the function of the transplants and the content of hexokinase, but none for the other estimated muscle enzymes, such as malate dehydrogenase (MDH), creatine kinase (CK), and lactic dehydrogenase (LDH). All enzyme levels were lower than in normal muscles. The results of this experimental series underline the utility of muscle transplantation with microneurovascular anastomoses to restore lost muscle function, even in the extremities, when strong forces are needed.
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PMID:Experimental free-muscle transplantation with microneurovascular anastomoses. 683 65

Michaelis constants for MgATP with yeast hexokinase vary from 28 microM with D-mannose to above 4 mM for the slow ATPase reaction, with the different values reflecting the degree of synergism in binding of MgATP and the sugar substrate. The best substrates show the greatest synergism, but the correlation is not exact. Similar synergistic binding between MgADP or its methylene analogue and phosphorylated sugars is seen. Product inhibiton of MgADP vs. MgATP and vice versa appears noncompetitive at low levels of variable substrate but becomes competitive at high levels. These patterns show that MgATP can combine with E-glucose-6-P (Ki = 4 mM) and MgADP with E-glucose (Ki = 1.6 mM). Isotope partitioning studies with glucose or glucose-6-P have determined the rates of release of these substrates from binary and ternary complexes and, together with reverse isotope exchange studies and the product inhibition studies mentioned above, have shown that the kinetic mechanism is a somewhat random one in which dissociation of sugars from productive ternary complexes is very slow, but release from nonproductive ternary complexes occurs at rates similar to those from binary enzyme-sugar complexes. D-Arabinose-5-P has a Km of 4.6 mM and a Vmax 5% that for glucose-6-P, confirming that the high Km for D-arabinose in the forward direction is caused by the low proportion in the furanose form. The dissociation constant of MgADP in the absence of sugars was determined from the Ki of 5.8 mM for MgADP as a competitive inhibitor vs. MgATP of the slow ATPase reaction.
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PMID:Substrate synergism and the kinetic mechanism of yeast hexokinase. 704 74

Rat liver mitochondria irradiated with external electric pulses (760 V/cm, 30 ms, rectangular) catalyzed net ATP synthesis of 0.055 nmol/mg protein/pulse. The amount of ATP synthesized increased on increasing the number, voltage and duration of the electric pulses. There was no apparent threshold voltage or duration for ATP synthesis in the ranges tested (0-760 V/cm and 0.05-30 ms). The energy applied to the mitochondrial membrane within a much shorter time than the turnover time of H+-ATPase must be stored in the membrane until it is utilized for ATP synthesis. Synthesis of ATP was inhibited by the specific H+-ATPase inhibitor aurovertin and by high concentrations of uncouplers. The energy transfer inhibitors oligomycin and dicyclohexylcarbodiimide had no effect on synthesis of ATP in mitochondria by electric pulses, but inhibited oxidative phosphorylation under the same conditions. In contrast to the pulse-driven ATP synthesis in subchloroplast particles, that in intact mitochondria required hexokinase-glucose, higher ADP concentration, lower osmolarity and protection against the pH effect of the electrodes.
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PMID:Net adenosine triphosphate synthesis driven by an external electric field in rat liver mitochondria. 709 14

The relationship between the respiration rate and the intra- and extramitochondrial adenine nucleotides was investigated in isolated rat liver mitochondria. For the determination of adenine nucleotide patterns in both compartments a new procedure was developed, based on the evaluation of these metabolites from incubation of various amounts of mitochondria under identical stationary states of oxidative phosphorylation. These identical states were adjusted by addition of appropriate amounts of hexokinase to a glucose-containing incubation mixture. Adenine nucleotides were measured in aliquots of the total extract of the incubation mixture without any separation. The concentrations of the adenine nucleotides in both compartments were obtained from a plot of the total concentration of these species versus mitochondrial protein. Disturbances of this method by unspecific efflux of adenine nucleotides could be excluded. The results obtained for the total adenine nucleotide content (12 nmol . mg-1 protein) and the intramitochondrial [ATP]/[ADP] ratio (about 4 in the resting state) are in good agreement with data obtained by other methods. Strong evidence is provided for a decrease in the intramitochondrial [ATP]/[ADP] ratio with increasing rate of oxygen consumption. Therefore it is not necessary to assume a microcompartmentation of the intramitochondrial adenine nucleotide pool in respect to the ATPase reaction and the adenine nucleotide translocation.
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PMID:Investigation of the dependence of the intramitochondrial [ATP]/[ADP] ratio on the respiration rate. 723 31

The mechanochemical ATPase kinesin is thought to move membrane-bounded organelles along microtubules in fast axonal transport. However, fast transport includes several classes of organelles moving at rates that differ by an order of magnitude. Further, the fact that cytoplasmic forms of kinesin exist suggests that kinesins might move cytoplasmic structures such as the cytoskeleton. To define cellular roles for kinesin, the axonal transport of kinesin was characterized. Retinal proteins were pulse-labeled, and movement of radiolabeled kinesin through optic nerve and tract into the terminals was monitored by immunoprecipitation. Heavy and light chains of kinesin appeared in nerve and tract at times consistent with fast transport. Little or no kinesin moved with slow axonal transport indicating that effectively all axonal kinesin is associated with membranous organelles. Both kinesin heavy chain molecular weight variants of 130,000 and 124,000 M(r) (KHC-A and KHC-B) moved in fast anterograde transport, but KHC-A moved at 5-6 times the rate of KHC-B. KHC-A cotransported with the synaptic vesicle marker synaptophysin, while a portion of KHC-B cotransported with the mitochondrial marker hexokinase. These results suggest that KHC-A is enriched on small tubulovesicular structures like synaptic vesicles and that at least one form of KHC-B is predominantly on mitochondria. Biochemical specialization may target kinesins to appropriate organelles and facilitate differential regulation of transport.
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PMID:Fast axonal transport of kinesin in the rat visual system: functionality of kinesin heavy chain isoforms. 753 59

After tissue homogenization, 43% of the total hexokinase activity found in maize radicles was recovered in the mitochondrial fraction and 35% was soluble, in the cytosol. The maize submitochondrial particles obtained after mitochondrial sonication retained a high hexokinase activity. The mitochondrial respiration (state 4 rate) was activated by glucose. This activation was blocked by carboxyatractyloside (0.5 mM) and by oligomycin (2 micrograms/ml). The affinities for ATP and glucose of both soluble and membrane-bound maize hexokinases are similar to those of yeast hexokinase. The Km for ATP of these different forms of hexokinase varied between 0.15 and 0.37 mM, and the Km for glucose between 0.05 and 0.13 mM. A major difference between the two maize hexokinase forms is that only the mitochondrial enzyme was strongly inhibited by ADP (Ki 0.04 mM). The soluble forms of hexokinase found both in the cytosol of maize radicles and in yeast are not inhibited by ADP. In a previous report [de Meis, Grieco and Galina (1992) FEBS Lett. 308, 197-201] it was shown that the mitochondrial F1-F0-ATPase can use glucose 6-phosphate and yeast hexokinase as an ATP regenerating system. We now show that the membrane-bound hexokinase and glucose 6-phosphate can also serve as an ATP regenerating system for the mitochondria of maize radicles provided that the ADP concentration is kept below 0.05 mM. Higher ADP concentrations inhibit the reverse reaction of the mitochondrial hexokinase.
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PMID:Different properties of the mitochondrial and cytosolic hexokinases in maize roots. 761 43

The effect of DL alpha-lipoic acid on the nephrotoxic potential of gentamicin was examined. Intraperitoneal injection of gentamicin (100 mg/kg/day) to rats resulted in decreased activity of the glycolytic enzymes-hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase. The two gluconeogenic enzymes--glucose-6-phosphatase and fructose-1,6-diphosphatase, the transmembrane enzymes namely the Na+, K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and the brushborder enzyme alkaline phosphatase, also showed decreased activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush border membrane damage. Decreased activity of the TCA cycle enzymes isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), suggests a loss in mitochondrial integrity. These biochemical disturbances were effectively counteracted by lipoic acid administration. Lipoic acid administration by gastric intubation at two different concentrations (10 mg and 25 mg/kg/day) brought about an increase in the activity of the glycolytic enzymes, ATPases and the TCA cycle enzymes. The gluconeogenic enzymes however showed a further decrease in their activities at both the concentrations of lipoic acid administered. These observations shed light on the nephroprotective action of lipoic acid against experimental aminoglycoside toxicity and the protection afforded at 25 mg/kg/day of lipoic acid was noted to be higher than that at 10 mg level.
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PMID:Role of DL alpha-lipoic acid in gentamicin induced nephrotoxicity. 765 73

Using 3D searching techniques based on algorithms derived from graph theory, we have established two previously unreported structural similarities involving the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT). First, we report that there is a strong similarity between the 3D folds of the RNase H domain of RT and the 'ATPase folds' of hexokinase, the 70 kDa heat-shock cognate protein and actin. Like RNase H, these enzymes are involved in nucleotide binding and metal ion-catalysed cleavage of a phosphodiester bond. Similarities of the folding motif and the position of the metal-binding site in these enzymes suggest possible functional analogies and evolutionary relationships with RNase H. Second, we find there is a strong resemblance between the folds of the RNase H domain and of the p66 and p51 'connection' domains of RT. It is possible that this striking similarity within the RT structure indicates a possible ancestral gene doubling event. The similarity may also indicate that the connection domains possess functional roles in addition to those previously suggested, and they may therefore represent a further target for the design of therapeutic agents.
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PMID:Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques. 768 87

Samples were taken at slaughter from heart and both locomotor and nonlocomotor muscles from animals of similar body weight but adapted to different levels of activity: three horses and three steers. All samples were analyzed biochemically to measure the activity of key metabolic enzymes. The skeletal muscles were analyzed histochemically for fibre type composition, fibre area and capillary supply. The general pattern of differences in fibre type composition and metabolic profile between muscle groups was similar in both horses and steers. The hearts of both species had high citrate synthase (CS), 3-OH-acylCoA-dehydrogenase (HAD) and hexokinase (HK) and low lactate dehydrogenase (LDH) activities. In both species, deep portions of muscles and muscles localized deeper in the body had a more oxidative metabolic profile than superficial portions and muscles. Taking all muscles into account, it was found that CS and HAD were higher and LDH lower in horse than in steer muscles. Horse muscles contained more type IIA fibres and had a higher capillary supply than steer muscles. There was no difference between the two species regarding mean fibre area. The adaptation of the horse to a higher level of activity in comparison with steers was reflected in a higher oxidative capacity, better vascularization and a larger proportion of type IIA fibres. It was also obvious from these results that the ATPase fibre-typing system does not reflect the metabolic profile of a muscle.
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PMID:Fibre type distribution, capillarization and enzymatic profile of locomotor and nonlocomotor muscles of horses and steers. 770 35

Glucokinase is distinguished from yeast hexokinase and low Km mammalian hexokinases by its low affinity for glucose and its cooperative behavior, even though glucose binding residues and catalytic residues are highly conserved in all of these forms of hexokinase. The roles of Ser-151 and Asn-166 as determinants of hexose affinity and cooperative behavior of human glucokinase have been evaluated by site-directed mutagenesis, expression and purification of the wild-type and mutant enzymes, and steady-state kinetic analysis. Mutation of Asn-166 to arginine increased apparent affinity for both glucose and ATP by a factor of 3. Mutation of Ser-151 to cysteine, alanine, or glycine lowered the Km for glucose by factors of 2-, 26-, and 40-fold, respectively, decreased Vmax, abolished cooperativity for glucose, and also decreased Km for mannose and fructose. The Ser-151 mutants had hexose Km values similar to those of yeast hexokinase, hexokinase I, and the recombinantly expressed COOH-terminal half of hexokinase I. However, the Ki values for the competitive inhibitors, N-acetylglucosamine and glucose-6-P, were unchanged, suggesting that Ser-151 is not important for inhibitor binding. Mutation of Ser-151 also increased the Km for ATP about 5-fold and abolished the enzyme's low ATPase activity, which indicates it is essential for ATP hydrolysis. The substrate-induced change in intrinsic fluorescence of S151A occurred at a much lower glucose concentration than that for wild-type enzyme. The results implicate a dual role for Ser-151 as a determinant of hexose affinity and catalysis, exclusive of the glucose-induced conformational change, and suggest that the low hexose affinity of glucokinase is dependent on interaction of Ser-151 with other regions of the protein.
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PMID:Human beta-cell glucokinase. Dual role of Ser-151 in catalysis and hexose affinity. 773 Mar 77


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