PubMed Health⌕ Search

Biomedical subjects

J E Wilson

Publications and source records attributed to J E Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Interaction of mitochondrially bound rat brain hexokinase with intramitochondrial compartments of ATP generated by oxidative phosphorylation and creatine kinase.

Previous work led to the conclusion that, during oxidative phosphorylation, mitochondrially bound hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) from rat brain was dependent on intramitochondrially compartmented ATP as substrate. The present study demonstrated that, when oxidative phosphorylation was functioning concurrently, mitochondrial creatine kinase could also generate intramitochondrial ATP serving as substrate for hexokinase. In the absence of concurrent oxidative phosphorylation, the kinetics of glucose phosphorylation with ATP generated by creatine kinase were not consistent with the supply of ATP from a saturable intramitochondrial compartment as formed during oxidative phosphorylation. Evidence for intramitochondrially compartmented ATP, generated by creatine kinase, was obtained; this was distinct from compartmented ATP generated by oxidative phosphorylation in terms of kinetics of generation of the compartment and its capacity, sensitivity to release by carboxyatractyloside, and sensitivity to disruption by digitonin. That oxidative phosphorylation did induce a dependence on intramitochondrial ATP as a substrate was further indicated by the observation that, although the initial rate of glucose phosphorylation by mitochondrial hexokinase depended on the extramitochondrial concentration of ATP present at the time oxidative phosphorylation was initiated, a final steady state rate of glucose phosphorylation was attained that was independent of extramitochondrial ATP levels. These and previous results emphasize the probable importance of nucleotide compartmentation in regulation of cerebral glycolytic and oxidative metabolism.

Adenosine Diphosphate↗
PubMed1992

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals↗
PubMed1992

Coordinated regulation of cerebral glycolytic and oxidative metabolism, mediated by mitochondrially bound hexokinase dependent on intramitochondrially generated ATP.

Hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) of rat brain mitochondria is associated with membrane regions thought to correspond to contact sites (regions of close interaction of the inner and outer mitochondrial membranes). Two intramitochondrial compartments of ATP also appear to be located at contact sites, and are dependent on oxidative phosphorylation for their generation. Neither of these compartments was associated with the intermembranal space containing adenylate kinase, nor was there detectable intramitochondrial compartmentation of ATP generated by the adenylate kinase reaction. Formation of these compartments was not dependent on the presence of bound hexokinase since equivalent amounts of compartmented ATP were found in mitochondria from which a major portion of the hexokinase had been removed by treatment with Glc-6-P. During active oxidative phosphorylation, mitochondrially bound hexokinase is totally dependent upon intramitochondrially compartmented ATP as a substrate. Both the levels of ATP in the intramitochondrial compartments and the rate of glucose phosphorylation by mitochondrially bound hexokinase were shown to be correlated with the rate of oxidative phosphorylation. This dependence of hexokinase on intramitochondrial ATP levels that reflect the status of mitochondrial oxidative metabolism provides a mechanism by which hexokinase can serve as a mediator, coordinating the rate at which glucose is introduced into the glycolytic pathway with terminal oxidative stages of metabolism and avoiding the accumulation of lactate which has been associated with toxic effects on the brain.

Adenosine Triphosphate↗
PubMed1992

Localization of the type III isozyme of hexokinase at the nuclear periphery.

The distribution of the type III isozyme of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) in rat kidney, liver, spleen, lung, and brain was determined immunohistochemically, using a monoclonal antibody generated against the enzyme purified from rat Novikoff hepatoma. In all tissues, specific cell types exhibited intense staining at the nuclear periphery, as confirmed by analysis using confocal microscopy. Isolated nuclei from kidney or liver were devoid of detectable type III hexokinase, although the enzyme was found in the "soluble" fraction from kidney or liver homogenates; these results suggest that the type III isozyme is associated in a labile manner with the external surface of the nucleus, with this association being disrupted by conventional homogenization and nuclear isolation procedures. The nuclear localization of the type III isozyme contrasts with previously demonstrated association of the type I and II isozymes with mitochondria. The physiological significance of a nuclear localization for the type III isozyme remains unclear. However, it was noted that many of the cells exhibiting prominent nuclear staining for type III hexokinase are endothelial or epithelial cells, suggesting a possible relationship between nuclear type III hexokinase and transport functions which are prominent in such cells.

Animals↗
PubMed1992

Epitopic regions recognized by monoclonal antibodies against rat brain hexokinase: association with catalytic and regulatory function.

Using direct and competitive epitope mapping methods, 23 monoclonal antibodies (Mabs) against rat brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) were divided into nine groups, each recognizing epitopes within defined surface regions of the N- or C-terminal domains; the latter have been associated with regulatory or catalytic functions, respectively. Reactivity of Mabs with the isolated domains was also studied. Based on the effect of various ligands on immunoreactivity, specific regions involved in ligand-induced conformational changes were identified. Adjacent epitopic regions, designated Regions F and G and located in the N- and C-terminal domains, respectively, were selectively affected by inhibitory hexose 6-phosphates (or analogs), marking these regions as being involved in transmission of the conformational signal from the regulatory N-terminal domain to the catalytic C-terminal domain. Consistent with this, the Ki for inhibition of the enzyme by the glucose 6-phosphate analog, 1,5-anhydroglucitol-6-phosphate, was markedly increased by Mabs binding in these regions, but unaffected by Mabs binding elsewhere in the molecule. Reactivity with Mabs recognizing conformationally sensitive epitopes in Region H of the C-terminal domain was greatly decreased by binding of substrate hexoses that induce closure of a cleft in the catalytic domain; selective recognition of the "open cleft" conformation, thereby preventing closure of the cleft required for progression of the catalytic cycle, can account for the marked decrease in Vmax that results from binding of these Mabs. Reactivity with Mabs binding to Region H was also decreased in the presence of inhibitory hexose 6-phosphates, implying that cleft closure was also induced by the latter; this is consistent with the suggestion that limitation of access to the C-terminal ATP binding site, resulting from cleft closure, is a factor in inhibition of the enzyme.

Amino Acid Sequence↗
PubMed1992

Functional consequences of mutation of highly conserved serine residues, found at equivalent positions in the N- and C-terminal domains of mammalian hexokinases.

Despite the extensive sequence similarity between the N- and C-terminal halves of the 100-kDa molecular weight mammalian hexokinases (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), reflecting their evolutionary origin by duplication and fusion of a gene coding for a smaller ancestral hexokinase, there is evidence for a functional division, with the C-terminal domain retaining a catalytic role while the N-terminal domain serves a regulatory function [binding of the product inhibitor, glucose 6-phosphate) (Glc-G-P)]. Conversion of Ser603 to Ala in the C-terminal domain of rat Type I hexokinase, expressed in COS-1 cells, resulted in drastic reduction of catalytic activity; Ser603 is analogous to Ser158, a residue of critical catalytic importance in the homologous yeast hexokinase. In contrast, conversion of Ser155 to Ala in the N-terminal domain (analogous to Ser603 in the C-terminal domain) of rat Type I hexokinase had no effect on catalytic activity or on inhibition of the enzyme by the Glc-6-P analog, 1,5-anhydroglucitol-6-P. Immunoreactivity with monoclonal antibodies recognizing conformationally sensitive epitopes was not affected, indicating that neither mutation resulted in gross structural perturbation. These results are consistent with the assignment of catalytic function, involving Ser603, to the C-terminal domain, and demonstrate that the analogous Ser155 is not critical for either catalytic or regulatory function. The Type I isozyme, expressed in COS-1 cells, retained the ability to bind to mitochondria in a Glc-6-P-sensitive manner, as previously found with the enzyme isolated from mammalian tissues.

Animals↗
PubMed1992

Using paramedics to identify at-risk elderly.

OBJECTIVES: To evaluate paramedics' ability to identify elderly at risk and refer them for assessment and service. DESIGN: A prospective nonrandomized open trial. SETTING: Akron, Ohio, a midsize city with a well-developed advanced life support emergency medical services system. TYPE OF PARTICIPANTS: One hundred thirty firefighter paramedics evaluated 6,000 elderly patients. Assessments were performed by trained geriatric assessors. INTERVENTION: Regardless of the reason for the call, paramedics screened all emergency medical services users age 60 and older for medical, mental health, social, and environmental problems. Identified cases were referred to the Area Agency on Aging for assessment and follow-up. MAIN RESULTS: Paramedics identified 197 people with possible problems, 124 of whom received an assessment. The remainder could not be assessed due to death, moving, referral, or transfer to a long-term care facility. Assessors confirmed the presence of a problem in 121 of 124 assessed cases, a positive predictive value of 98%. The program was useful for 94 people, 48% of those identified and assessed. CONCLUSION: Paramedics can serve as case finders for at-risk elderly, and effective linkage to service agencies can occur.

Aged↗
PubMed1992

A decade of acceptable autopsy rates. Does concordance of clinician and pathologist views explain relative success?

In an attempt to better understand the basis and significance of an annual autopsy rate consistently over 45% for the past decade, we recently investigated the attitudes and practices of 36 pathologists and 176 clinicians in our institution with respect to the function of the autopsy service and the utility of the autopsy. The autopsy report was "not used in a consistent manner" by 57% of clinical respondents. Several clinicians thought that autopsy reports were too long (20%) and too slow (38%), but not with the frequency that pathologists did, 73% and 58%, respectively. Significantly more pathologists than clinicians believed autopsy rates have fallen over the past 20 years because (1) people think that everything about the deceased is already known, (2) medical students are poorly educated about the autopsy, (3) pathologists have diminished interest, (4) physicians fear litigation, (5) physicians fear "being wrong," (6) pathologists lack financial incentives, and (7) Joint Commission on Accreditation of Healthcare Organizations requirement is not in place. Perceptions regarding the frequency of major discrepancies between clinical and autopsy findings were comparable, 17% and 13%, for pathologists and clinicians, respectively. Our "high" institutional autopsy rate does not reflect concordance of perceptions expressed by clinicians and pathologists and, thus, other factors may be important in the maintenance of an acceptable rate.

Attitude of Health Personnel↗
PubMed1992

Progress in blood lipid reporting practices by clinical laboratories in North America. Changes from 1985 to 1990.

In an attempt to assess the impact of the National Cholesterol Education Program recommendations and to provide follow-up to a 1985 survey of blood lipid reporting practices in 152 academic clinical laboratories in North America, the same laboratories were resurveyed regarding current blood lipid-reporting practices. All 97 laboratories that responded to our survey routinely measured serum total cholesterol, while 94% measured high-density lipoprotein cholesterol, 99% measured triglycerides, 26% apolipoproteins A1 and B, and a single laboratory measured apolipoprotein E. There was a marked downward shift in reference ranges for serum total cholesterol used by laboratories in 1990 compared with 1985. Of the laboratories responding to both surveys, 90% lowered their reported reference values. Changes in the sources of reference ranges were also noted. The percent of laboratories using reference ranges based on age and sex fell from 52% to 21% and from 31% to 10%, respectively. The number of laboratories designating patient risk for coronary heart disease rose from 31% to 72%. Currently, 61% of laboratories designating risk use the National Cholesterol Education Program guidelines for serum total cholesterol. The use of other risk designations, including high-density lipoprotein--cholesterol, total cholesterol to high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, and apolipoproteins changed only modestly during the 5-year interval. The current reporting patterns reflect simplified and more uniform practices apparently in response to the National Cholesterol Education Program.

Adult↗
PubMed1991

Effect of ligand binding on the tryptic digestion pattern of rat brain hexokinase: relationship of ligand-induced conformational changes to catalytic and regulatory functions.

The Type I isozyme of rat hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is comprised of N- and C-terminal domains, associated with regulatory and catalytic functions, respectively. Extensive sequence similarity between the domains is consistent with evolution of the enzyme by gene duplication and fusion. Cleavage at tryptic sites located in the C-terminal domain is markedly sensitive to ligands present during digestion, while analogous sites in the N-terminal domain are either resistant to trypsin or unaffected by the presence of ligands. These results imply a lack of structural equivalence between the N- and C-terminal domains, with the overall structure of the N-terminal domain being "tighter" and with a major component of ligand-induced conformational changes being focused in the C-terminal domain. Based on a previously proposed structure for brain hexokinase, protection by substrate hexoses is attributed to substrate-induced closing of a cleft in the C-terminal domain. Similar protection at C-terminal cleavage sites results from binding of inhibitory hexose-6-phosphates to the N-terminal domain. In addition, hexose-6-phosphates evoke cleavage at a site, T5, located in a region that has been associated with binding of ATP to the C-terminal domain. Thus, alterations in this region, coupled with reduced accessibility resulting from cleft closure, may account for the mutually exclusive binding of inhibitory hexose-6-phosphates and substrate ATP. In the absence of Mg2+, all nucleoside triphosphates examined (ATP, UTP, CTP, and GTP) protected against digestion by trypsin. In contrast, ATP-Mg2+ stabilized the C-terminal domain but destabilized the N-terminal domain, while the chelated forms of the other nucleoside triphosphates were similar to the unchelated forms in their effect on proteolysis; the unique response to ATP-Mg2+ reflects the specificity for ATP as a substrate.

Adenosine Triphosphate↗
PubMed1991

Substrate inhibition of the human immunodeficiency virus type 1 reverse transcriptase.

Substrate inhibition was observed with the heterodimeric (p66/p51) and the homodimeric (p66/p66, p51/p51) forms of human immunodeficiency virus type 1 reverse transcriptase (RNA-dependent DNA polymerase, EC 2.7.7.49). An apparent Ki value of 195 +/- 37 microM was determined for dTTP using the bacterial cloned and expressed heterodimer. Similar values were obtained with the homodimeric and the virus-encoded enzymes. When poly-(rC).p(dG)10 was used as template-primer, dGTP exhibited substrate inhibition with an apparent Ki value of 189 +/- 32 microM. Substrate inhibition was not observed with dTTP when DNA.DNA template-primers were used. Hill coefficients for substrate binding determined in the presence of saturating concentrations of template-primer were equal to 1.0, suggesting that substrate inhibition of the heterodimer is not the result of an allosteric mechanism involving the p51 subunit. Furthermore, UV crosslinking experiments with [gamma-32P]dTTP showed crosslinking only to the p66 subunit. Substrate inhibition was not as pronounced with other retroviral reverse transcriptases as it was with human immunodeficiency type 1 reverse transcriptase.

Adenosine Triphosphate↗
PubMed1991

Complete amino acid sequence of the type II isozyme of rat hexokinase, deduced from the cloned cDNA: comparison with a hexokinase from novikoff ascites tumor.

The 917-residue amino acid sequence of the Type II isozyme of rat hexokinase has been deduced from the nucleotide sequence of cloned cDNA. The sequences of 197 nucleotides in the 5' untranslated region and 687 bases of the 3' untranslated region have also been determined. A region of overlap between two discrete cDNA clones was confirmed by isolation and sequencing of a genomic DNA clone that spanned the region. Within this region, the 634-nucleotide coding sequence was divided into three exons, each of 150-250 nucleotides; these results suggest that the gene encoding Type II hexokinase is likely to be quite complex. There is extensive similarity between the sequences of the N- and C-terminal halves of the Type II isozyme, as previously seen with the Type I and III isozymes; this is consistent with the view that these enzymes evolved by a process of gene duplication and fusion. A cDNA encoding the entire C-terminal half of a hexokinase from Novikoff ascites tumor cells was also isolated and found to be identical to a cDNA encoding the corresponding region of the Type II isozyme of skeletal muscle. Northern analysis indicated that a single mRNA, approx 5200 nucleotides in length, encoded both the skeletal muscle and the tumor enzymes. These results do not support previous speculation that the hexokinase isozymes of normal tissue are distinct from those of tumors, and suggest the possibility that post-translational modifications of a single protein species might account for apparent differences between the isozymes of normal and tumor tissues.

Amino Acid Sequence↗
PubMed1991

Chelation of divalent cations by ATP, studied by titration calorimetry.

Thermodynamic parameters and stoichiometry for the formation of complexes of ATP with Mg2+, Ca2+, and Sr2+ were determined by titration calorimetry. In each case, 1:1 stoichiometry was observed and complex formation was entropy driven. Binding constants for formation of complexes decreased in the order of Mg2+ greater than Ca2+ greater than Sr2+, as expected from charge density considerations. Monovalent cations hindered complex formation with Mg2+, apparently by competing with the divalent cation for complexation with ATP. Analysis of this competitive effect provided estimates of the binding constants for complexes of ATP with monovalent cations, which decreased in the order expected from charge density considerations (Li+ greater than Na+ greater than K+).

Adenosine Triphosphate↗
PubMed1991

Hexokinase of rat brain mitochondria: relative importance of adenylate kinase and oxidative phosphorylation as sources of substrate ATP, and interaction with intramitochondrial compartments of ATP and ADP.

Interactions between intramitochondrial ATP-generating, ADP-requiring processes and ATP-requiring, ADP-generating phosphorylation of glucose by mitochondrially bound hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) have been investigated using well-coupled mitochondria isolated from rat brain. ADP generated by mitochondrially bound hexokinase was more effective at stimulating respiration than was ADP generated by hexokinase dissociated from the mitochondria, and pyruvate kinase was less effective as a scavenger of ADP generated by the mitochondrially bound hexokinase than was the case with ADP generated by the dissociated enzyme. These results indicate that ADP generated by the mitochondrially bound enzyme is at least partially sequestered and directed toward the mitochondrial oxidative phosphorylation apparatus. Under the conditions of these experiments, the maximum rate of ATP production by oxidative phosphorylation was approximately 10-fold greater than the maximum rate of ATP generation by the adenylate kinase reaction. Moreover, during periods of active oxidative phosphorylation, adenylate kinase made no detectable contribution to ATP production. Thus, adenylate kinase does not represent a major source of ATP for hexokinase bound to actively phosphorylating brain mitochondria. With adenylate kinase as the sole source of ATP, a steady state was attained in which ATP formation was balanced by utilization in the hexokinase reaction. In contrast, when oxidative phosphorylation was the source of ATP, a steady state rate of Glc phosphorylation was attained, but it was equivalent to only about 40-50% of the rate of ATP production and thus there was a continued net increase in ATP concentration in the system. Rates of Glc phosphorylation with ATP generated by oxidative phosphorylation exceeded those seen with equivalent levels of exogenously added ATP. Moreover, at total ATP concentrations greater than approximately 0.2 mM, hexokinase bound to actively phosphorylating mitochondria was unresponsive to continued slow increases in ATP levels; acute increase in ATP (by addition of exogenous nucleotide) did, however, result in increased hexokinase activity. The relative insensitivity of mitochondrially bound hexokinase to extramitochondrial ATP suggested dependence on an intramitochondrial pool (or pools) of ATP during active oxidative phosphorylation. Two intramitochondrial compartments of ATP were identified based on their selective release by inhibitors of electron transport or oxidative phosphorylation. These compartments were distinguished by their sensitivity to inhibitors and the kinetics with which they were filled with ATP generated by oxidative phosphorylation. Exogenous glycerol kinase competed effectively with mitochondrially bound hexokinase for extramitochondrial ATP, with relatively low levels of glycerol kinase completely inhibiting phosphorylation of Glc.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1991

Complete amino acid sequence of the type III isozyme of rat hexokinase, deduced from the cloned cDNA.

Clones containing cDNA coding for the Type III isozyme of rat hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) were isolated from a library prepared in lambda gt10 with rat liver mRNA. Three clones were characterized. Their composite sequence includes the entire coding region for Type III hexokinase, 3' untranslated sequence extending into the polyadenylated region, and 80 bp of 5' untranslated sequence. Extensive similarity in sequence of N- and C-terminal halves of the enzyme, previously seen with the Type I isozyme, is consistent with the view that these 100-kDa mammalian hexokinases are the evolutionary result of duplication and fusion of a gene coding for an ancestral hexokinase having a molecular weight of approximately 50 kDa. Extensive similarities are seen between sequences of the Type I and III isozymes, and those reported for mammalian glucokinase (also called Type IV hexokinase) and for the hexokinase and glucokinase of yeast. Residues thought to be involved in catalytic function are highly conserved in all of these enzymes. Based on a quantitative comparison of sequence similarities, it is concluded that the 50-kDa mammalian glucokinase is more closely related to the 100-kDa mammalian enzymes than it is to the 50-kDa enzymes from yeast. One interpretation of this might be that the mammalian glucokinase arose by resplitting of the gene coding for the 100-kDa mammalian hexokinases.

Amino Acid Sequence↗
PubMed1991

Disposition of mitochondrially bound hexokinase at the membrane surface, deduced from reactivity with monoclonal antibodies recognizing epitopes of defined location.

A panel of monoclonal antibodies against rat brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) has been employed to investigate the orientation of the mitochondrially bound enzyme on the mitochondrial surface. Based on their ability to immunoprecipitate truncated forms of the protein, obtained by in vitro translation of truncated versions of the mRNA, the epitopes for seven monoclonal antibodies were mapped to regions consisting of 20-50 amino acid residues within the sequence of the N-terminal half of the enzyme. There is extensive sequence similarity between the N- and C-terminal halves of this enzyme, which is thought to have evolved by a process of gene duplication and fusion. However, these antibodies react selectively with epitopes in the N-terminal half, and thus epitopic regions for several of these antibodies could be further defined by eliminating from consideration regions showing substantial sequence similarity with the C-terminal half. The epitope for one of the monoclonal antibodies, designated 4D4, was shown to involve the extreme N-terminus of the enzyme; selective proteolytic modification of this region resulted in loss of immunoreactivity. Relative location of epitopes for three other antibodies, designated 2B, 1C5, and 4C5, within a 20-residue segment was deduced from effects of modifying sulfhydryl residues within this segment on immunoreactivity. Thus, by a combination of sequence analysis and experimental methods, the epitopes for these seven antibodies could be localized to defined regions within the overall sequence. The ability of these antibodies to prevent binding of hexokinase to mitochondria, and their ability to recognize the mitochondrially bound enzyme, provided a basis for assessing the relative proximity of the corresponding epitopes to the mitochondrial surface when the enzyme was bound. The disposition of the bound enzyme on the mitochondrial surface was deduced by relating these results to the proposed structure for brain hexokinase.

Amino Acid Sequence↗
PubMed1991

Hexokinase levels in discrete regions of rat brain: evaluation by quantitative immunofluorescence using interactive laser cytometry and comparison with basal rates of glucose utilization.

Relative levels of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) have been determined in 16 discrete regions of adult rat brain by a quantitative immunofluorescence method. The distribution of immunofluorescence in brain sections was determined by interactive laser cytometry and related to hexokinase content by comparison with standard sections containing known amounts of the enzyme. In many of these regions, referred to here as group I regions, hexokinase content was correlated with previously reported basal rates of glucose utilization. However, several regions (group II regions) in which hexokinase content exceeded that expected from basal rates of glucose utilization were also detected. Compared with the corresponding regions from albino rat brain, higher hexokinase levels were found in the dorsal and ventral lateral geniculate (group I regions) of pigmented Norway rats, a result reflecting previously reported increased glucose utilization by these regions in pigmented rats. There was no difference in hexokinase levels in the superior colliculus, a group II structure, from albino and pigmented rats, a finding implying that a reported increase in rate of glucose utilization in the superior colliculus of pigmented rats is effected without an increase in hexokinase content. It is suggested that group II regions may be adapted to sustain increases in rates of glucose utilization that are, relative to basal rates, considerably greater than those experienced by group I regions.

Animals↗