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)

Molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined by means of molecular biology. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia. To date, 47 gene mutations have been identified. We identified one base deletion, one splicing mutation, and six distinct missense mutations in 12 unrelated families with a homozygous PK deficiency. Mutations located near the substrate or fructose-1,6- diphosphate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the most common metabolic disorder, and it is associated with chronic hemolytic anemia and/or drug- or infection-induced acute hemolytic attack. An estimated 400 million people are affected worldwide. The mutations responsible for about 78 variants have been determined. Some have polymorphic frequencies in different populations. Most variants are produced by one or two nucleotide substitutions. Molecular studies have disclosed that most of the class 1 G6PD variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in deficiencies of glucosephosphate isomerase, (TPI), phosphoglycerate kinase, and adenylate kinase. Compound heterozygosity with missense mutation and base deletion has been determined in deficiencies of hexokinase and diphosphoglyceromutase. Compound heterozygosity with missense and nonsense mutations has been identified in TPI deficiency. One base junction mutations resulting in abnormally spliced PFK-M mRNA have been identified in homozygous PFK deficiency. An exception is hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from the overproduction of a structurally normal enzyme.
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PMID:Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: tabulation of mutant enzymes. 857 52

A total of 958 blood samples from Muria, Maria, Bhattra and Halba from the Bastar District in Madhya Pradesh (India) was collected and analyzed for glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase, hexokinase, and adenylate kinase red cell enzyme deficiency using flourescent technique. The implications of findings of the presence of rare enzyme deficiencies are discussed.
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PMID:Red cell enzyme deficiencies in the tribal population groups of the Bastar District, Madhya Pradesh, India. 857 39

The effectiveness of gossypol as an antifertilizing agent is due to the severe injuries or death that this drug produces on spermatozoa and spermatides. Several in vitro and in vivo studies have shown that spermatozoal lactic and malic dehydrogenases are inhibited by gossypol; and that these are more susceptible than the somatic enzymes. Notwithstanding, the in vivo effects on other somatic enzymes have been poorly analyzed. The present study shows that gossypol did not produce toxic effects on eight erythrocytic enzymes of male hamsters that were fed daily with 20 mg of gossypol/kg, for 1, 3, 5 or 10 days. The enzymatic activities analyzed were: adenylate kinase, hexokinase, glucose-6-phosphatase, glucose phosphoisomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglyceratokinase and pyruvate kinase.
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PMID:Orally administered gossypol has no effect on eight hamster erythrocytic enzymes. 874 2

Guanidinopropionic acid (GPA), an analogue of creatine (Cr), is known to inhibit Cr uptake by cells. The metabolic effects of chronic Cr depletion on brain, heart and soleus muscle of rats were studied. In GPA hearts and soleus muscle, total specific creatine kinase (CK) activity was decreased by approx. 40% compared to controls, whereas in brain this same activity was elevated by a factor of two. Immunoblot analysis of soleus mitochondria from GPA rats showed an approximate 4-fold increase in Mi-CK protein and a concomitant 3-fold increase in adenine nucleotide translocator (ANT) protein, when compared to control. In GPA-fed rats, the specific activities of adenylate kinase (ADK) and succinate dehydrogenase were significantly higher in brain and soleus (2-fold), but heart remained the same. However, hexokinase (HK) decreased by approx. 50% both in heart and soleus, indicating that muscle and brain follow different strategies to compensate the energy deficit caused by creatine depletion. Skinned muscle fibres from Cr-depleted soleus attained approx. only 70% maximum state 3 respiration with 0.1 M ADP in the presence of 10 mM Cr compared to 100% in control fibres. This defect in Cr stimulated respiration was also seen in isolated heart mitochondria, but was normal in those from brain. The observed deficit of Cr-stimulated respiration, the significant accumulation of Mib-CK and ANT, concomitant with the formation of Mib-CK rich intra-mitochondrial inclusions shown by electron microscopy, indicate that Mib-CK function and coupling to oxidative phosphorylation (OXPHOS), is impaired in these abnormal mitochondria. In addition, our results show tissue-specific metabolic compensations to Cr depletion.
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PMID:Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain. 881 48

Dextran M20 was added to isolated rat liver mitochondria to mimic cytosolic macromolecules. Under these conditions, the morphological changes in the mitochondrial periphery that occur upon isolation of the organelle are restored, i.e. the volume of the intermembrane space decreases and the contact site frequency increases. The ADP routing from mitochondrial kinases at various locations was investigated by using the activities of oxidative phosphorylation and externally added pyruvate kinase as sensors for ADP transport into the matrix and extramitochondrial compartment, respectively. The studies reveal that a significant fraction of the ADP generated by either adenylate kinase in the intermembrane space or by outer membrane bound hexokinase isozyme I, is not accessible to extramitochondrial pyruvate kinase. Quantitative information on the ADP compartmentation in rat liver mitochondria was obtained by comparing the ADP supply from mitochondrial kinases to oxidative phosphorylation with that of non-bound, extramitochondrially located kinases. This approach allowed us to estimate the ADP diffusion gradients which were present across the outer membrane and between the compartment formed by bound hexokinase and the extramitochondrial compartment. In the presence of 10% dextran M20 these ADP gradients amounted to approximately 12 microM. The possible role of mitochondrial kinases in ADP transport into mitochondria in vivo is discussed.
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PMID:Experimental evidence for dynamic compartmentation of ADP at the mitochondrial periphery: coupling of mitochondrial adenylate kinase and mitochondrial hexokinase with oxidative phosphorylation under conditions mimicking the intracellular colloid osmotic pressure. 930 64

The effect of sprint training and detraining on supramaximal performances was studied in relation to muscle enzyme adaptations in eight students trained four times a week for 9 weeks on a cycle ergometer. The subjects were tested for peak oxygen uptake (VO2peak), maximal aerobic power (MAP) and maximal short-term power output (Wmax) before and after training and after 7 weeks of detraining. During these periods, biopsies were taken from vastus lateralis muscle for the determination of creatine kinase (CK), adenylate kinase (AK), glycogen phosphorylase (PHOS), hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and its isozymes, 3-hydroxy-acyl-CoA dehydrogenase (HAD) and citrate synthase (CS) activities. Training induced large improvements in Wmax (28%) with slight increases (3%) in VO2peak (P < 0.10). This was associated with a greater glycolytic potential as shown by higher activities for PHOS (9%), PFK (17%) and LDH (31%) after training, without changes in CK and oxidative markers (CS and HAD). Detraining induced significant decreases in VO2peak (4%), MAP (5%) and oxidative markers (10-16%), while Wmax and the anaerobic potential were maintained at a high level. This suggests a high level in supramaximal power output as a result of a muscle glycogenolytic and glycolytic adaptation. A long interruption in training has negligible effects on short-sprint ability and muscle anaerobic potential. On the other hand, a persistent training stimulus is required to maintain high aerobic capacity and muscle oxidative potential. This may contribute to a rapid return to competitive fitness for sprinters and power athletes.
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PMID:Enzyme adaptations of human skeletal muscle during bicycle short-sprint training and detraining. 942 50

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessed in situ in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/- 10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.
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PMID:Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure. 992 74

Coupling of ATP-generating with ATP-consuming processes is an essential component in the cardiac bioenergetics responsible for optimal myocardial function. Although a number of enzymatic systems have been implicated in securing proper intracellular energy communication, their integrative response in a failing myocardium has not been determined so far. Therefore, we measured catalytic activities of enzymes responsible for the communication between ATP-generating and ATP-consuming processes in ventricular samples obtained from normal dogs and dogs with tachycardia-induced heart failure. In the failing myocardium, phosphotransfer activities of creatine kinase, adenylate kinase, 3-phosphoglycerate kinase and pyruvate kinase, which collectively deliver ATP and remove ADP from myofibrillar ATPases, were depressed by 30, 21, 44 and 20%, respectively, when compared to normal controls. The activity of hexokinase, an enzyme which directs phosphoryls into the glycolytic phosphotransfer pathway, was unchanged. Also, the activity of glyceraldehyde-3-phosphate dehydrogenase, which may shuttle inorganic phosphate between ATPases and ATP-synthases, was not affected by heart failure. However, the CO2-hydration activity of carbonic anhydrase, which together with creatine kinase, is presumed responsible for removal of protons from ATPases, was diminished by 21%. As these enzymatic systems are collectively required for adequate delivery of high-energy phosphoryl to, and removal of end-products from, cellular ATPases, the cumulative deficit in their flux capacities may provide a bioenergetic basis for impaired contraction-relaxation in the failing heart.
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PMID:Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium. 1063 Jun 20

The delimitation of cryptic species within the main vector of the American visceral leishmaniasis, Lutzomyia longipalpis, remains a topic of controversy. An analysis of genetic variability based on 8 enzymatic loci revealed fixed differences in 2 diagnostic loci, adenylate kinase (Ak) and hexokinase (Hk), between sympatric and allopatric populations at 4 localities in Venezuela. The absence of heterozygotes for these 2 loci within 1 locality indicates, for the first time, the presence of 2 sympatric reproductively isolated populations or cryptic species within L. longipalpis. Significant differences were also detected between these cryptic species in the allele frequencies of glucose-6-phosphate isomerase (Gpi) and malate dehydrogenase, decarboxylating (Me). One species showed mean heterozygosities that ranged between 6.6% and 6.7%, with 1.6-1.9 alleles detected per locus, while the other had mean heterozygosities that ranged from 4.3% to 6.3%, with 1.3-1.6 alleles per locus. Comparisons of isozyme profiles with published data suggests that 1 species is similar to the L. longipalpis described in Colombian and Brazilian populations, whereas the other has not been previously reported.
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PMID:Occurrence of sibling species of Lutzomyia longipalpis (Diptera: Psychodidae) in Venezuela: first evidence from reproductively isolated sympatric populations. 1067 86

In vitro enzyme-based ATP regeneration systems are important for improving yields of ATP-dependent enzymatic reactions for preparative organic synthesis and biocatalysis. Several enzymatic ATP regeneration systems have been described but have some disadvantages. We report here on the use of polyphosphate:AMP phosphotransferase (PPT) from Acinetobacter johnsonii strain 210A in an ATP regeneration system based on the use of polyphosphate (polyP) and AMP as substrates. We have examined the substrate specificity of PPT and demonstrated ATP regeneration from AMP and polyP using firefly luciferase and hexokinase as model ATP-requiring enzymes. PPT catalyzes the reaction polyP(n) + AMP --> ADP + polyP(n-1). The ADP can be converted to ATP by adenylate kinase (AdK). Substrate specificity with nucleoside and 2'-deoxynucleoside monophosphates was examined using partially purified PPT by measuring the formation of nucleoside diphosphates with high-pressure liquid chromatography. AMP and 2'-dAMP were efficiently phosphorylated to ADP and 2'-dADP, respectively. GMP, UMP, CMP, and IMP were not converted to the corresponding diphosphates at significant rates. Sufficient AdK and PPT activity in A. johnsonii 210A cell extract allowed demonstration of polyP-dependent ATP regeneration using a firefly luciferase-based ATP assay. Bioluminescence from the luciferase reaction, which normally decays very rapidly, was sustained in the presence of A. johnsonii 210A cell extract, MgCl(2), polyP(n=35), and AMP. Similar reaction mixtures containing strain 210A cell extract or partially purified PPT, polyP, AMP, glucose, and hexokinase formed glucose 6-phosphate. The results indicate that PPT from A. johnsonii is specific for AMP and 2'-dAMP and catalyzes a key reaction in the cell-free regeneration of ATP from AMP and polyP. The PPT/AdK system provides an alternative to existing enzymatic ATP regeneration systems in which phosphoenolpyruvate and acetylphosphate serve as phosphoryl donors and has the advantage that AMP and polyP are stabile, inexpensive substrates.
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PMID:In vitro ATP regeneration from polyphosphate and AMP by polyphosphate:AMP phosphotransferase and adenylate kinase from Acinetobacter johnsonii 210A. 1078 79


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