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PubMed1993

Direct observation of hexokinase translocation in stimulated macrophages.

1. Fluorescence imaging of antibodies was used to show that phorbol 12-myristate 13-acetate (PMA) induces a 4-fold increase in the amount of hexokinase relative to the control in the cortical shell of rat peritoneal macrophage cytosol adjacent to the plasma membrane, and a corresponding depletion in the amount of hexokinase in the central core of the cytosol. However, there was no significant PMA-dependent change in the distribution of glucose-6-phosphate dehydrogenase. 2. Cytochalasin D, an inhibitor of actin microfilament polymerization, prevented the PMA-induced hexokinase translocation and also reduced the PMA-dependent increases in 2-deoxy-D-glucose transport and glucose-dependent PMA-stimulated superoxide production. 3. PMA caused a contraction of the width of the cortical F-actin zone. Cytochalasin D caused some dispersal of F-actin within the cell, increasing the density of F-actin within the central cytosolic core and causing aggregation of the F-actin within the cortex. These data are consistent with the view that PMA induces attachment of hexokinase to microfilaments within the cortical zone adjacent to the cell membrane of macrophages, and cytochalasin D prevents this attachment. This is the first direct demonstration of the translocation of hexokinase to the plasma membrane in activated cells, and supports the view that enhanced hexokinase activity in the cortical region of the cytosol is an important early component of the macrophage activation process.

Actins↗
PubMed1977

High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase.

A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. However, when glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is found to be high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Moreover, tumor hexokinase activity is not inhibited by low concentrations (<0.6 mM) of the reaction product glucose 6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is found associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. In contrast, glucose has no effect on the respiration of mitochondria from control and regenerating liver. These results suggest that the high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell.

Aerobiosis↗
PubMed1979

Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations.

The aluminum present as a contaminant in ATP preparations can cause strong inhibition of yeast hexokinase P-II activity at pH 7.0 or below but has little or no inhibitory effect at a pH of 7.5 or greater. The inhibition is reversed by citrate, 3-phosphoglycerate, malate, phosphate, and catecholamines, all of which have previously been described as activators of hexokinase at low pH. We suggest that these agents activate the enzyme only by virtue of their ability to coordinate with aluminum present in the assay system. The presence of aluminum is also responsible for the "negative cooperativity" observed at low pH with respect to Mg . ATP concentration--i.e., the inhibition by aluminum is uncompetitive at low Mg . ATP concentrations but becomes competitive at high Mg . ATP concentrations. The inhibition is thought to be due to formation of a complex of Al . ATP with the enzyme, with a dissociation constant (Ki) of 0.1 microM. Yeast hexokinase P-I is somewhat less sensitive to A1 than is hexokinase P-II, and yeast glucokinase is not detectably affected. The hexokinase in rat brain (type I) shows a pH-dependent inhibition by Al similar to that observed with the yeast hexokinases, whereas the rat muscle (type II) enzyme is less sensitive, suggesting a possible relationship to aluminum encephalopathy in man.

Adenosine Triphosphate↗
PubMed1985

High glucose concentrations partially release hexokinase from inhibition by glucose 6-phosphate.

The phosphorylation of glucose by human erythrocyte hexokinase follows classical Michaelis-Menten kinetics; hexokinase manifests maximum activity at 5 mM glucose, and no further increase in activity can be measured at higher glucose concentrations. However, the erythrocytes of diabetics and normal erythrocytes incubated with high concentrations of glucose contain increased concentrations of glucose 6-phosphate. To elucidate the mechanism of accumulation of glucose 6-phosphate when erythrocytes are exposed to high glucose concentrations, hexokinase activity was examined in the presence of naturally occurring inhibitors, such as glucose 1,6-bisphosphate, 2,3-diphosphoglycerate, ADP, and glucose 6-phosphate at physiological concentrations. Without inhibitors or in the presence of glucose 1,6-bisphosphate,2,3-diphosphoglycerate, and ADP, maximum hexokinase activity was observed at 5 mM glucose concentration. On the contrary, in the presence of glucose 6-phosphate, hexokinase activity increased at glucose concentrations greater than 5 mM; inhibition by glucose 6-phosphate was partially competitive with glucose. The relief by glucose of glucose 6-phosphate inhibition of hexokinase is a possible explanation of the increased glucose 6-phosphate level in diabetic erythrocytes.

Diabetes Mellitus↗
PubMed1992

Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes.

It has been proposed that endogenous hexokinases of the pancreatic beta cell control the rate of glucose-stimulated insulin secretion and that genetic defects that reduce beta-cell hexokinase activity may lead to diabetes. To test these hypotheses, we have produced transgenic mice that have a 2-fold increase in hexokinase activity specific to the pancreatic beta cell. This increase was sufficient to significantly augment glucose-stimulated insulin secretion of isolated pancreatic islets, increase serum insulin levels in vivo, and lower the blood glucose levels of transgenic mice by 20-50% below control levels. Elevation of hexokinase activity also significantly reduced blood glucose levels of diabetic mice. These results confirm the role of beta-cell hexokinase activity in the regulation of insulin secretion and glucose homeostasis. They also provide strong support for the proposal that reductions in beta-cell hexokinase activity can produce diabetes.

Animals↗
PubMed2000

The high resolution crystal structure of yeast hexokinase PII with the correct primary sequence provides new insights into its mechanism of action.

Hexokinase is the first enzyme in the glycolytic pathway, catalyzing the transfer of a phosphoryl group from ATP to glucose to form glucose 6-phosphate and ADP. Two yeast hexokinase isozymes are known, namely PI and PII. The crystal structure of yeast hexokinase PII from Saccharomyces cerevisiae without substrate or competitive inhibitor is determined and refined in a tetragonal crystal form at 2.2-A resolution. The folding of the peptide chain is very similar to that of Schistosoma mansoni and previous yeast hexokinase models despite only 30% sequence identity between them. Distinct differences in conformation are found that account for the absence of glucose in the binding site. Comparison of the current model with S. mansoni and yeast hexokinase PI structures both complexed with glucose shows in atomic detail the rigid body domain closure and specific loop movements as glucose binds. A hydrophobic channel formed by strictly conserved hydrophobic residues in the small domain of the hexokinase is identified. The channel's mouth is close to the active site and passes through the small domain to its surface. The possible role of the observed channel in proton transfer is discussed.

Animals↗
PubMed2002

Variability in glucose transporter-1 levels and hexokinase activity in human melanoma.

Melanoma exhibits heterogeneous growth patterns and widely varying sensitivities to multiple treatment modalities. This variability may reflect intrinsic genetic differences in factors giving rise to altered metabolism. Glucose is the primary energy source of tumours, including melanoma, and glucose transporter isoform 1 (Glut-1) and hexokinase are key rate-limiting factors in glucose metabolism. The levels of Glut-1 and total hexokinase activity were measured in 31 melanoma biopsies to determine the extent of tumour-to-tumour variability in these parameters. Relative Glut-1 levels were determined by Western immunoblot analysis using human anti-Glut-1 rabbit polyclonal antibody, and hexokinase activity was measured in the same samples by an enzymatic assay monitoring the reduction in the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) (in nmol NADP+ reduced/min per mg protein). All melanomas were from patients who had received no therapy prior to surgery. Immediately after excision, tumour biopsies were disaggregated to single cells by collagenase and DNase and frozen in liquid nitrogen. Thirty human melanomas exhibited a 22-fold variation in levels of Glut-1 and 29 exhibited a nine-fold variation in total cellular hexokinase activity. Glut-1 levels and hexokinase activity were not correlated with one another. The broad range in Glut-1 levels and hexokinase activity observed between melanomas suggests that these glycolytic rate-limiting parameters that influence the rate of glucose metabolism may contribute to the variability in melanoma response to treatment modalities.

Adult↗
PubMed1987

Proteolysis of hexokinase PII is not the triggering signal of carbon catabolite derepression in Saccharomyces cerevisiae.

The role of hexokinase PII in mediating carbon catabolite derepression in yeast has been examined. Hexokinase isoenzyme PII (EC 2.7.1.1) was partially degraded when protease inhibitors were omitted from the buffer used for preparation of cell-free extracts. The hexokinase PII inactivation induced by D-xylose was correlated with derepression of maltase (EC 3.2.1.20) in the wild-type strain Saccharomyces cerevisiae G-517 and in D.308.3, a strain that contains the cloned hexokinase PII gene on a multicopy plasmid. This inactivation was not correlated with the loss of hexokinase PII protein as assayed by immunoblotting. We conclude that during the derepression process there is no release of proteolytic peptides from hexokinase PII.

Carbon↗
PubMed1999

Novel alleles of yeast hexokinase PII with distinct effects on catalytic activity and catabolite repression of SUC2.

In the yeast Saccharomyces cerevisiae, glucose or fructose represses the expression of a large number of genes. The phosphorylation of glucose or fructose is catalysed by hexokinase PI (Hxk1), hexokinase PII (Hxk2) and a specific glucokinase (Glk1). The authors have shown previously that either Hxk1 or Hxk2 is sufficient for a rapid, sugar-induced disappearance of catabolite-repressible mRNAs (short-term catabolite repression). Hxk2 is specifically required and sufficient for long-term glucose repression and either Hxk1 or Hxk2 is sufficient for long-term repression by fructose. Mutants lacking the TPS1 gene, which encodes trehalose 6-phosphate synthase, can not grow on glucose or fructose. In this study, suppressor mutations of the growth defect of a tps1delta hxk1delta double mutant on fructose were isolated and identified as novel HXK2 alleles. All six alleles studied have single amino acid substitutions. The mutations affected glucose and fructose phosphorylation to a different extent, indicating that Hxk2 binds glucose and fructose via distinct mechanisms. The mutations conferred different effects on long- and short-term repression. Two of the mutants showed very similar defects in catabolite repression, despite large differences in residual sugar-phosphorylation activity. The data show that the long- and short-term phases of catabolite repression can be dissected using different hexokinase mutations. The lack of correlation between in vitro catalytic hexokinase activity, in vivo sugar phosphate accumulation and the establishment of catabolite repression suggests that the production of sugar phosphate is not the sole role of hexokinase in repression. Using the set of six hxk2 mutants it was shown that there is a good correlation between the glucose-induced cAMP signal and in vivo hexokinase activity. There was no correlation between the cAMP signal and the short- or long-term repression of SUC2, arguing against an involvement of cAMP in either stage of catabolite repression.

Alleles↗
PubMed1999

Overexpression of Arabidopsis hexokinase in tomato plants inhibits growth, reduces photosynthesis, and induces rapid senescence.

Sugars are key regulatory molecules that affect diverse processes in higher plants. Hexokinase is the first enzyme in hexose metabolism and may be a sugar sensor that mediates sugar regulation. We present evidence that hexokinase is involved in sensing endogenous levels of sugars in photosynthetic tissues and that it participates in the regulation of senescence, photosynthesis, and growth in seedlings as well as in mature plants. Transgenic tomato plants overexpressing the Arabidopsis hexokinase-encoding gene AtHXK1 were produced. Independent transgenic plants carrying single copies of AtHXK1 were characterized by growth inhibition, the degree of which was found to correlate directly to the expression and activity of AtHXK1. Reciprocal grafting experiments suggested that the inhibitory effect occurred when AtHXK1 was expressed in photosynthetic tissues. Accordingly, plants with increased AtHXK1 activity had reduced chlorophyll content in their leaves, reduced photosynthesis rates, and reduced photochemical quantum efficiency of photosystem II reaction centers compared with plants without increased AtHXK1 activity. In addition, the transgenic plants underwent rapid senescence, suggesting that hexokinase is also involved in senescence regulation. Fruit weight, starch content in young fruits, and total soluble solids in mature fruits were also reduced in the transgenic plants. The results indicate that endogenous hexokinase activity is not rate limiting for growth; rather, they support the role of hexokinase as a regulatory enzyme in photosynthetic tissues, in which it regulates photosynthesis, growth, and senescence.

Arabidopsis↗
PubMed1980

Isoelectric focusing of hexokinase and glucose-6-phosphate dehydrogenase isoenzymes in erythrocytes of newborn infants and adults.

Isoenzymes of glucose-6-phosphate dehydrogenase and hexokinase from red cells of newborn infants were analysed by isoelectric focusing in polyacrylamide gel after partial purification. The pattern of isoenzyme distribution was compared with that of erythrocytes from adults. Glucose-6-phosphate dehydrogenase isoenzyme distribution was identical between erythrocytes from newborn infants and adults. Erythrocytic hexokinase isoenzymes patterns were different between newborn infants and adults. Erythrocytes from adults contain a hexokinase isoenzyme which has the same isoelectric point as rat liver hexokinase isoenzyme I (pH 6 . 01). This isoenzyme is lacking in red cells from newborn infants. Isoenzymes with the isoelectric properties of rat liver isoenzyme II (pH 5 . 48) were not detectable in red cells from adults, nor from newborn infants. The occurrence of an isoenzyme III in red cells remained unclear, because only a faint staining was observed in the corresponding region of erythrocytic gels. Preliminary results revealed a fetal type of hexokinase isoenzyme distribution in infants with an age of 10 months. This indicates that regulation of the synthesis of Hb F and of fetal hexokinase isoenzymes is not correlated.

Adult↗
PubMed1996

Characterisation of the Aspergillus nidulans frA1 mutant: hexose phosphorylation and apparent lack of involvement of hexokinase in glucose repression.

Hexose phosphorylation was studied in Aspergillus nidulans wild-type and in a fructose non-utilising mutant (frA). The data indicate the presence of at least one hexokinase and one glucokinase in wild-type A. nidulans, while the frA1 mutant lacks hexokinase activity. The A. nidulans gene encoding hexokinase was isolated by complementation of the frA1 mutation. The absence of hexokinase activity in the frA1 mutant did not interfere with glucose repression of the enzymes involved in alcohol and L-arabinose catabolism. This suggest that, unlike the situation in yeast where mutation of hexokinase PII abolishes glucose repression, the A. nidulans hexokinase might not be involved in glucose repression.

Amino Acid Sequence↗
PubMed1998

Insulin does not change the intracellular distribution of hexokinase in rat heart.

Preliminary evidence has suggested that hexokinase in rat heart changes its kinetic properties in response to insulin through translocation to the outer mitochondrial membrane. We reexamined this hypothesis in light of tracer kinetic evidence to the contrary. Our methods were as follows. Working rat hearts were perfused with Krebs-Henseleit buffer containing glucose (5 mmol/l) and sodium oleate (0.4 mmol/l). Dynamic glucose uptake was measured with [2-3H]glucose and with 2-deoxy-2-[18F]fluoroglucose (2-[18F]DG). Hexokinase activity was determined in the cytosolic and mitochondrial fractions. Our results are as follows. Uptake of glucose and uptake of 2-[18F]DG were parallel. Insulin (1 mU/ml) increased glucose uptake threefold but had no effect on 2-[18F]DG uptake. The tracer-to-tracee ratio decreased significantly. The Michaelis-Menten constant of hexokinase for 2-deoxyglucose was up to 10 times higher than for glucose. There was no difference in maximal reaction velocity. Two-thirds of hexokinase was bound to mitochondria. Insulin neither caused translocation nor changed Michaelis-Menten constant or maximal reaction velocity. In conclusion, the insulin-induced changes in the tracer-to-tracee ratio are due to a shift of the rate-limiting step for glucose uptake from transport to phosphorylation by hexokinase. Insulin does not affect the intracellular distribution or the kinetics of hexokinase.

Animals↗
PubMed1978

Particulate and free hexokinase in fetal rat liver.

The association of hexokinase with particulate fractions of liver has been studied during the development of the rat. In the fetal rat liver about 50% of the total hexokinase is bound to the mitochondria. This proportion decreases gradually after birth. No association of hexokinase with mitochondria could be demonstrated in the adult rat liver. It is suggested that the binding of hexokinase to the mitochondria is a consequence of a property which is lost during development of the mitochondrial membranes. At least part of the hexokinase is rather tightly bound to the mitochondria. Glucose-6-phosphate or ATP do not solubilize the enzyme. The proportion of hexokinase bound to the mitochondria is independent of the metabolic state of the hepatocyte as exemplified by studies with inhibitors of oxidative phosphorylation, using the digitonin technique for the separation of particulate and cytosol fractions of isolated fetal rat hepatocytes.

Adenosine Triphosphate↗
PubMed1999

[Cooperation of membrane proteins and cytosolic proteins in metabolic regulation--involvement of binding of hexokinase to mitochondria in regulation of glucose metabolism and association and complex formation between membrane proteins and cytosolic proteins in regulation of active oxygen production].

Changes in amount and activity of enzyme protein are critical factors in regulating intracellular metabolisms. However, since the metabolisms are proceeding in environment with complex architecture consisted of various membranes, spatial factors should be taken into consideration for the regulation. In this review, involvement of interaction between cytosolic and membrane proteins in metabolic regulation are discussed. It had been reported that hexokinase activity was found in mitochondrial fraction in spite of almost exclusive distribution of other glycolytic enzymes to soluble fraction, the tendency being marked in the brain and many types of tumor cells whereas mitochondrial hexokinase activity was quite low in the liver. Interested in such enzyme and tissue specificities, we investigated the significance and mechanism of the unique intracellular distribution of hexokinase. We found that mitochondria-bound hexokinase was more active than the cytosolic type in producing glucose 6-phosphate (G6P), probably due to the advantage in utilizing ATP produced in mitochondria. In addition, we also found that the binding stabilized hexokinase against G6P inhibition. As to the binding, it was reported that G6P released hexokinase from mitochondria while Mg2+ promoted the binding. In this respect, we found that polyamines promoted the binding at much lower concentration than that of Mg2+, and mitochondria-bound form had small hydrophobic domain at terminal region for the binding to porin on the outer membrane. Then, we found a protease which specifically cleaved the domain with little effect on catalytic activity and molecular size of the bindable form. Such a modifying protease was purified and identified as lysosomal cathepsin L. The protease activity was high in the liver and low in the brain, suggesting that the difference in the activity was responsible for the afore-mentioned tissue specificity. On the other hand, we examined regulatory mechanism for active oxygen production in neutrophils, since the production of superoxide anion (O2-) by NADPH oxidase was very low at the resting state while markedly increased on phagocytosis and chemical stimulation. Since the stimulants for the activation were so various in chemical nature, we postulated mechanism to converge the stimulation to the activation. Incidentally, we found increase in phosphorylation of 46-47 K protein, irrespective of the type of stimulation. Use of inhibitors and examination on the phosphorylation condition indicated protein kinase C (PKC) as the phosphorylating enzyme. In addition, we observed the 46-47 K protein existed in cytosol at resting state, while it was translocated to cell membranes in concurrence with the phosphorylation. Similar findings were obtained in many laboratories and those proteins were named cytosolic activating factors (and then p47-phox, etc.). These proteins associate with membrane proteins to constitutes the active from of NADPH oxidase. Next, we examined mechanism to shut off the O2- production, and found that the inactivation through disassembly of the constituents was attained by dephosphorylation of phosphorylated p47-phox by cytosolic protein phosphatase. Then we have also found that protein kinases other than PKC were involved in regulation of NADPH oxidase activity. Though phosphorylation of p47-phox etc. is deeply involved in the activation of NADPH oxidase, membrane perturbation, so-called priming, is required for the activation. We also reported some possible indications for the priming, and possible involvement of cytoskeletons in O2- production. Apart from protein phosphorylation, it has been reported that amphiphilic acidic compounds are potent activator for NADPH oxidase. We also have examined their effects to find that these compounds also caused the assembly of the NADPH oxidase constituents. Reversely, amphiphilic basic compounds suppressed suggesting significance of introduction of negative charge in NADPH oxidase activat

Animals↗
PubMed1975

Studies on the mechanism of orthophosphate regulation of bovine brain hexokinase.

An attempt was made to gain insight into the mechanism of orthophosphate attenuation of glucose-6-P inhibition of bovine brain hexokinase I (ADP:D-hexose 6-phosphotransferase, EC 2.7.1.1) from experiments of ligand binding and initial rate kinetics. Studies of glucose-6-P and phosphate binding to hexokinase reveal one binding site per hexokinase molecule. A model is presented which is consistent with the binding and kinetic data currently available on the alleviation of glucose-6-P inhibition of brain hexokinase by phosphate. The model implies that hexokinase may exist in equilibrium either as a free or phosphate-associated enzyme. The kinetic parameters of the two enzyme forms are similar except in their ability to bind glucose-6-P. It is suggested that the dissociation constant for glucose-6-P is relatively very high for hexokinase to which phosphate is bound. Phosphate appears to bind at an allosteric site on the enzyme, whereas glucose-6-P is associated either at the active site or at an allosteric site which overlaps the catalytic site.

Adenosine Triphosphate↗
PubMed1987

Effect of methohexital on the relationship between hexokinase distribution and energy metabolism in neuroblastoma cells.

Cultured neuroblastoma cells (clone neuro-2a) were used to demonstrate the influence of an anesthetic on energy metabolism by acting on the intracellular distribution of hexokinase activity. First of all, there was to be shown that a relationship between the intracellular hexokinase distribution and energy metabolism actually exists in neuroblastoma cells. Since glucose-6-phosphate could be assumed to be the main regulator of this enzyme distribution, experimental conditions were chosen where the glucose-6-phosphate level was changed significantly. A decrease in the glucose-6-phosphate level in the cells was achieved by deprivation of glucose and oxygen for 30 min. Under these conditions the glucose-6-phosphate level and the soluble hexokinase activity decreased significantly. The effect was reversible when glucose and oxygen were again added to the incubation medium of the cells. On the other hand, the antimetabolite 6-aminonicotinamide produced an accumulation of glucose-6-phosphate which caused an increase in the soluble hexokinase activity. These results brought evidence for a correlation of intracellular hexokinase distribution and energy metabolism. When alpha-(+/-)-5-allyl-1-methyl-5-(1-methyl-2-pentinyl) barbituric acid (methohexital) was added to the incubation medium of the neuroblastoma cells, a dose-dependent increase in soluble hexokinase activity was measurable, whereas the glucose-6-phosphate level was decreased at least within a therapeutically relevant dosage range of the anesthetic. This effect was reversible when methohexital was washed out from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1979

Purification of a hexokinase-binding protein from the outer mitochondrial membrane.

Brain hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) binds selectively to the outer membrane of rat liver mitochondria but not to inner mitochondrial or microsomal membranes nor to the plasma membrane of human erythrocytes. A protein having subunit molecular weight of 31,000, determined by sodium dodecyl sulfate-gel electrophoresis, has been highly purified from the outer mitochondrial membrane by repetitive solubilization with octyl-beta-D-glucopyranoside followed by reconstitution into membranous vesicles when the detergent is removed by dialysis. When incorporated into lipid vesicles, the protein confers the ability to bind brain hexokinase in a Glc-6-P-sensitive manner as is seen with the intact outer mitochondrial membrane. Hexokinase binding ability and the 31,000 subunit molecular weight protein co-sediment during sucrose density gradient centrifugation. Both hexokinase binding ability and the 31,000 subunit molecular weight protein are resistant to protease treatment of the intact outer mitochondrial membrane while other membrane proteins are extensively degraded. It is concluded that this protein, designated the hexokinase-binding protein (HBP), is an integral membrane protein responsible for the selective binding of hexokinase by the outer mitochondrial membrane.

Animals↗