Activities of glucokinase and hexokinase in mammalian and avian livers

Stanley, John C.; Dohm, G. Lynis; McManus, Bronwyn; Newsholme, Eric A.

doi:10.1042/bj2240667

Cited by 33 publications

(13 citation statements)

References 25 publications

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“…Despite the remarkable increase in net hepatic glucose uptake, however, the hepatic G-6-P concentration was not significantly increased at the end of the experimental period. One possibility is that flux through glucokinase (GK) was maximal in the control state, but because GK is not inhibited by G-6-P and is half-saturated at 10-15 mM (16,45), and because glucose uptake increased during hyperglycemia, this cannot be the case. Therefore, the discordance between hepatic glucose and G-6-P levels suggests that flux out of G-6-P increased proportionally to the rate of entry into the pool.…”

Section: Discussionmentioning

confidence: 90%

Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog

Edgerton

Cardin

Neal

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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The aim of these studies was to investigate the effect of hyperglycemia with or without hyperinsulinemia on hepatic gluconeogenic flux, with the hypothesis that inhibition would be greatest with combined hyperglycemia/hyperinsulinemia. A glycogen phosphorylase inhibitor (BAY R3401) was used to inhibit glycogen breakdown in the conscious overnight-fasted dog, and the effects of a twofold rise in plasma glucose level (HI group) accompanied by 1) euinsulinemia (HG group) or 2) a fourfold rise in plasma insulin were assessed over a 5-h experimental period. Hormone levels were controlled using somatostatin with portal insulin and glucagon infusion. In the HG group, net hepatic glucose uptake and net hepatic lactate output substantially increased. There was little or no effect on the net hepatic uptake of gluconeogenic precursors other than lactate (amino acids and glycerol) or on the net hepatic uptake of free fatty acids compared with the control group. Consequently, whereas hyperglycemia had little effect on gluconeogenic flux to glucose 6-phosphate (G-6- P), net hepatic gluconeogenic flux was reduced because of increased hepatic glycolytic flux during hyperglycemia. Net hepatic glycogen synthesis was increased by hyperglycemia. The effect of hyperglycemia on gluconeogenic flux to G-6- P and net hepatic gluconeogenic flux was similar. We conclude that, in the absence of appreciable glycogen breakdown, the increase in glycolytic flux that accompanies hyperglycemia results in decreased net carbon flux to G-6- P but no effect on gluconeogenic flux to G-6- P.

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Section: Discussionmentioning

confidence: 90%

Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog

Edgerton

Cardin

Neal

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…This contention is controversial; a number of groups have demonstrated that the activity of hepatic glucokinase is more than sufficient to support the rates of glycogen synthesis observed in vivo [13,32,33]. We consider that the low net glycogen synthesis from glucose in these systems is due, in large part, to an incomplete inhibition of glycogen degradation under these conditions.…”

Section: Resultsmentioning

confidence: 97%

Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose

Parniak

Kalant

1988

Biochemical Journal

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Glycogen synthesis in isolated hepatocytes can occur from glucose both by a direct mechanism and by an indirect process in which glucose is first metabolized to C3 intermediates before use for glycogenesis via gluconeogenesis. We studied the incorporation into glycogen of glucose and the gluconeogenic substrate, fructose, in primary cultures of hepatocytes from fasted rats. In the presence of insulin, both glucose and fructose promoted net deposition of glycogen; however, fructose carbon was incorporated into glycogen to a greater extent than that from glucose. When glucose and fructose were administered simultaneously, the glycogenic utilization of glucose was stimulated 2-3-fold, and that of fructose was increased by about 500. At constant hexose concentrations, the total incorporation of carbon, and the total accumulation of glycogen mass, from glucose and fructose when present together exceeded that from either substrate alone. Fructose did not change the relative proportion of glucose carbon incorporated into glycogen via the indirect (gluconeogenic) mechanism. The synergism of glucose and fructose in glycogen synthesis in isolated rat hepatocytes in primary culture appears to result from a decrease in the rate of degradation of newly deposited glycogen, owing to (i) decreased amount of phosphorylase a mediated by glucose and (ii) noncovalent inhibition of residual phosphorylase activity by some intermediate arising from the metabolism of fructose, presumably fructose 1-phosphate.

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“…The G6P effect was assessed by a radiometric assay using [ 14 C 1 ]mannose as a substrate as previously described [58] with slight modifications. The reaction medium used contained 75 mM Tris/HCl (pH 7.5), 7.5 mM MgCl 2 , 0.8 mM EDTA, 1.5 mM KCl, 2.5 mM ATP, 4 mM 2-mercaptoethanol, 0.1 % Triton X-100, 5 mM NaF, 5 mM NaN 3 and 2 mM [ 14 C 1 ]mannose ( 18.5 Bq/nmol; Amersham Pharmacia Biotech).…”

Section: Enzyme Activity Assaysmentioning

confidence: 99%

Characterization of non-cytosolic hexokinase activity in white skeletal muscle from goldfish (Carassius auratus L.) and the effect of cold acclimation

Santos

Diniz

Galina³

et al. 2010

Bioscience Reports

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HK (hexokinase) is an enzyme involved in the first step in the glucose metabolism pathway, converting glucose into G6P (glucose 6-phosphate). Owing to the importance of skeletal muscle for fish swimming and acclimation processes, we used goldfish (Carassius auratus L.) white muscle in order to investigate subcellular distribution and kinetics of HK. In this study, we report that HK activity is predominantly localized in the mitochondrial fraction [NC-HK (non-cytosolic HK)] in goldfish white muscle. Studies of the kinetic parameters revealed that the Km (Michaelis-Menten constant) for glucose was 0.41±0.03 mM and that for mannose was 3-fold lower, whereas the affinity for fructose was too low to be measured. The Km for ATP was 0.88±0.05 mM, whereas no activity was observed when either GTP or ITP was used as a phosphate donor. A moderate inhibition (20-40%) was found for ADP and AMP. Similar to mammalian HK, G6P and glucose analogues were able to promote an inhibition of between 85 and 100% of activity. Here, we found that acclimation of goldfish at 5°C promoted a 2.5-fold increase in NC-HK compared with its counterpart acclimated at 25°C. However, cytosolic HK activity was not altered after thermal acclimation. In summary, our results suggest that the goldfish has a constitutive NC-HK that shows some similarities to mammalian HK-II and, curiously, may play a role in the broad metabolic changes required during the cold acclimation process.

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Activities of glucokinase and hexokinase in mammalian and avian livers

Cited by 33 publications

References 25 publications

Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog

Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog

Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose

Characterization of non-cytosolic hexokinase activity in white skeletal muscle from goldfish (Carassius auratus L.) and the effect of cold acclimation

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