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)

Glycerol kinase of Trypanosoma brucei has been shown to be capable of catalysing sn-glycerol-3-phosphate dependent ADP phosphorylation for ATP generation. The rate of this reaction (Vr) is sufficient to account for the observed rate of glycerol production from anaerobic glucose metabolism by intact cells and to account for net ATP synthesis. Glycerol kinase has been purified by preparing a post-nuclear, particulate fraction and solubilizing the enzyme with 0.5% (w/v) Triton X-100. This treatment results in a 3.5-fold increase in total activity, demonstrating the latent nature of particulate glycerol kinase, and an overall 10-fold increase in specific activity in the soluble fraction. The ratio of the velocities of the forward (Vf) reverse (Vr) reactions of this enzyme is altered from 21 to 170 upon solubilization. The Michaelis constants for the solubilized enzyme are KmADP = 0.12 +/- 0.04 mM, KmG-3-P = 5.12 +/- 1.47 mM, Kmglycerol = 0.12 +/- 0.05 and KmATP = 0.19 +/- 0.04 mM. Endogenous hexokinase acts as an ATP trap favouring ATP synthesis sn-glycerol-3-phosphate and ADP. This can be demonstrated in reconstituted systems using trypanosome glycerol kinase and varying hexokinase activities. Mass action inhibition of ATP synthesis by glycerol is more marked with lower hexokinase activities. High glycerol kinase activity (> 0.5 mumol/min/mg protein) has been found in the T. brucei complex of trypanosomes that produce glycerol anaerobically whereas only low activities (less than or equal to 0.03 mumol/min/mg protein) are present in Trypanosoma cruzi, Trypanosoma lewisi and Crithidia fasciculata, organisms that do not produce glycerol. Trypanosoma congolense has a glycerol kinase activity of 0.17 mumol/min/mg protein and shows poorer ATP synthesis from anaerobic glucose metabolism than organisms of the T. brucei complex.
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PMID:Studies on glycerol kinase and its role in ATP synthesis in Trypanosoma brucei. 625 71

Twelve individuals have been described with glycerol kinase deficiency. Five of these individuals are adults who were noted incidentally to have pseudohypertriglyceridemia. Six of these individuals are children who manifest a clinical complex which includes adrenal hypoplasia/insufficiency and developmental delay. Another child has intermittent coma, a normal IQ, and no evidence of adrenal insufficiency. Genetic and biochemical hypotheses are proposed to explain this clinical variability. Glycerol kinase binds specifically and reversibly to the porin, the pore-forming protein of the outer mitochondrial membrane, which also binds hexokinase. Mutations affecting any component of this kinase-binding system will alter the properties of this system. Glycerol kinase deficiency, as an inborn error of this compartmented metabolic system, offers an investigational opportunity for studying this microenvironment.
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PMID:Human glycerol kinase deficiency: an inborn error of compartmental metabolism. 631 39

Glycerol kinase was found to associate with the hexokinase binding protein. The binding of glycerol kinase has a high specificity as illustrated by the fact that the magnitude of binding was reduced by glycerophosphate and antibodies against the hexokinase binding protein. A possible function of glycerol kinase binding to the mitochondria with respect to metabolic regulation is proposed for the following reasons: (i) Glycerol kinase seems to bind to the same binding protein as hexokinase. (ii) Both kinases were observed to be reversibly bound to the mitochondria in different metabolic situations, i.e., 10% of total cellular activity from both kinases is bound in starved rats whereas no activity of glycerol kinase and 30% of hexokinase become bound in fed rats. (iii) The kinetic properties of the associated glycerol kinase change in an analogous manner to those known for structure-bound hexokinase. (iv) With the binding of glycerol kinase to the mitochondria, it is possible to propose a metabolic pathway for glycerol oxidation to dihydroxyacetone phosphate by a combined action involving the enzyme, glycerol phosphate oxidase, and oxidative phosphorylation.
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PMID:The binding of glycerol kinase to the outer membrane of rat liver mitochondria: its importance in metabolic regulation. 631 40