Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selected enzymes were measured in mixed-fiber bundles and individual fibers from rat plantaris (PL) and soleus (Sol) muscles that had undergone either 2 wk of tetrodotoxin (TTX) inactivation of the sciatic nerve, a sham operation, or were contralateral to the TTX limb. TTX disuse caused severe wasting of PL (46%) and Sol (26%) muscles and of single fibers (50% and 40%, respectively). TTX PL and Sol also had reduced (50%) glycogen content. In TTX, PL, and Sol macro samples and single fibers, the activities (mol.h-1.kg dry wt-1) of hexokinase, glycogen phosphorylase, and lactate dehydrogenase were higher, lower, and unchanged, respectively, compared with controls. Single-fiber data showed that these changes occurred in all fibers. In TTX PL macro samples, activities of glycerol-3-phosphate dehydrogenase (GPDH), pyruvate kinase (PK), malate dehydrogenase (MDH), citrate synthase (CS), beta-hydroxyacyl-CoA dehydrogenase (BOAC), and thiolase were, or tended to be, lower. Single-fiber data showed a disappearance of high-oxidative moderate glycolytic fibers (i.e., usually fast-twitch oxidative in control) and the appearance of more fibers with a metabolic enzyme profile approaching that of control slow-oxidative fibers. In TTX Sol macro samples, GPDH and PK tended to be higher, and thiolase, BOAC, CS, and MDH lower. Single-fiber data corroborated these findings and suggested the appearance of fast fibers with downregulated oxidative enzyme profiles. Our results suggest that neuromuscular activity is a major, but not the sole, determinant of the size and metabolic heterogeneity that exists in muscle cells.
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PMID:Effects of tetrodotoxin-induced neural inactivation on single muscle fiber metabolic enzymes. 804 92

Mitochondrial hexokinase (HK) and creatine kinase (CK) known to form complexes with a voltage dependent anion channel (VDAC) have been reported to increase cell death resistance under hypoxia/anoxia. In this work we propose a new, non-Mitchell mechanism of generation of the inner and outer membrane potentials at anaerobic conditions. The driving force is provided by the Gibbs free energy of the HK and CK reactions associated with the VDAC-HK and the ANT (adenine nucleotide translocator)-CK-VDAC complexes, respectively, both functioning as voltage generators. In the absence of oxygen, the cytosolic creatine phosphate can be directly used by the ANT-CK-VDAC contact sites to produce ATP from ADP in the mitochondrial matrix. After that, ATP released through the fraction of unbound ANTs in exchange for ADP is used in the mitochondrial intermembrane space by the outer membrane VDAC-HK electrogenic complexes to convert cytosolic glucose into glucose-6-phosphate. A simple computational model based on the application of Ohm's law to an equivalent electrical circuit showed a possibility of generation of the inner membrane potential up to -160mV, under certain conditions, and of relatively high outer membrane potential without wasting of ATP that normally leads to cell death. The calculated membrane potentials depended on the restriction of ATP/ADP diffusion in narrow cristae and through the cristae junctions. We suggest that high inner membrane potential and calcium extrusion from the mitochondrial intermembrane space by generated positive outer membrane potential prevent mitochondrial permeability transition, thus allowing the maintenance of mitochondrial integrity and cell survival in the absence of oxygen.
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PMID:VDAC electronics: 2. A new, anaerobic mechanism of generation of the membrane potentials in mitochondria. 2456 93