Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia

Nguyen, Nga H.T.; González, Susana Villa; Hassel, Bjørnar

doi:10.1111/j.1471-4159.2006.04433.x

Cited by 24 publications

(14 citation statements)

References 34 publications

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“…The process of glyceroneogenesis leading to glycerol-3-phosphate in mammalian liver is an active area of research, because it is essential to the triglyceride/fatty acid cycle and is a target for treatment of type 2 diabetes (10,24,30). In addition, activity of a putative glycerol-3-phosphatase has been suggested in oxygen-limited rat heart and brain, although neither the protein nor the transcript have been identified (3,19). The current work with rainbow smelt presents an ideal model system to study the control mechanisms of glyceroneogenesis and the final step in glycerol production.…”

Section: Perspectives and Significancementioning

confidence: 98%

Low temperature directly activates the initial glycerol antifreeze response in isolated rainbow smelt (Osmerus mordax) liver cells

Clow¹,

Ewart²,

Driedzic³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Rainbow smelt (Osmerus mordax) accumulate high levels of glycerol in winter that serve as an antifreeze. Liver glycogen is a source of glycerol during the early stages of glycerol accumulation, whereas dietary glucose and amino acids are essential to maintain rates of glycerol synthesis. We presently report rates of glycerol and glucose production by isolated hepatocytes. Cells from fish held at 0.4 to -1.5 degrees C and incubated at 0.4 degrees C were metabolically quiescent with negligible rates of glycerol or glucose production. Hepatocytes isolated from fish maintained at 8 degrees C and incubated at 8 degrees C produced glucose but not glycerol. Glycerol production was activated in cells isolated from 8 degrees C fish and incubated at 0.4 degrees C without substrate or when glucose, aspartate, or pyruvate was available in the medium. Incubation at 0.4 degrees C without substrate resulted in similar molar rates of glucose and glycerol production in concert with glycogen mobilization. Glycogenolysis and glycerol production were associated with increases in total in vitro activities of glycogen phosphorylase and glycerol-3-phosphate dehydrogenase. Maximal in vitro activities of hexokinase and glucokinase were not influenced by temperature, but high activities of a low-K(m) hexokinase may serve to redirect glycogen-derived glucose to glycolysis as opposed to releasing it from the cells. Rates of glycerol production were not enhanced in cells from fish held at 8 degrees C and incubated at 0.4 degrees C with adrenergic or glucocorticoid stimulation. As such, low temperature alone is sufficient to activate the glycerol production mechanism and results in a shift from glucose to a mix of glucose and glycerol production.

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Section: Perspectives and Significancementioning

confidence: 98%

Low temperature directly activates the initial glycerol antifreeze response in isolated rainbow smelt (Osmerus mordax) liver cells

Clow¹,

Ewart²,

Driedzic³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The direct dephosphorylation of the G3P to glycerol has been proposed to be the pathway used in smelt to directly produce glycerol (5,8), as it is the case in some algae and yeasts producing high amounts of glycerol in response to environmental stresses (23,37). Activity of such an enzyme has been suggested in oxygenlimited rat heart and brain, although neither the protein nor the transcript have been identified in a vertebrate (4,22). Isolation and characterization of such an enzyme would be of interest, as it would open a new avenue of research concerning the role of glycerol in vertebrates.…”

Section: Perspectives and Significancementioning

confidence: 99%

Glycerol loss to water exceeds glycerol catabolism via glycerol kinase in freeze-resistant rainbow smelt (Osmerus mordax)

Ditlecadet

Short

Driedzic

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Rainbow smelt accumulate high amounts of glycerol in winter. In smelt, there is a predictable profile of plasma glycerol levels that starts to increase in November (<5 μmol/ml), peaks in mid-February (>200 μmol/ml), and thereafter decreases to reach the initial levels in the beginning of May. The aim of this study was to investigate the respective role of the two main mechanisms that might be involved in glycerol clearance from mid-February: 1) breakdown of glycerol to glycerol-3-phosphate through the action of the glycerol kinase (GK) and 2) direct loss toward the environment. Over the entire glycerol cycle, loss to water represents a daily loss of ∼10% of the total glycerol content of fish. GK activities were very low in all tissues investigated and likely have a minor quantitative role in the glycerol cycle. These results suggest that glycerol levels are dictated by the rate of glycerol synthesis (accelerated and deactivated during the accumulation and decrease stages, respectively). Although not important in glycerol clearance, GK in liver might have an important metabolic function for other purposes, such as gluconeogenesis, as evidenced by the significant increase of activity at the end of the cycle.

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“…Activity of this enzyme is consistent with rates of diffusive loss from the animal, increases during the transition to glycerol production, and is much lower than G3PDH activity implying that it is the rate-limiting step in the process. Putative G3P Pase activity has been shown in ischemic mammalian heart and brain (de Groot et al 1994;Nguyen et al 2007) and is potentially very critical in our understanding of metabolic regulation during oxygen limitation in that consideration must be given to glycerol production from sources other than triglycerides. Given its relatively high activity and inducibility, rainbow smelt liver is a potential tissue for the ultimate identification of a vertebrate G3P Pase.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Rainbow smelt: the unusual case of cryoprotection by sustained glycerol production in an aquatic animal

Driedzic

2015

J Comp Physiol B

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Rainbow smelt flourish at -1.8 °C, the freezing point of sea water. An antifreeze protein contributes to freeze point depression but, more importantly, cryoprotection is due to an elevation in osmotic pressure, by the accumulation of glycerol. The lower the water temperature, the higher the plasma glycerol with levels recorded as high as 400 mmol l(-1). Glycerol freely diffuses out in direct relation to the glycerol concentration and fish may lose as much as 15% of their glycerol reserve per day. Glycerol levels decrease from a maximum in February/March while water temperature is still sub-zero. The decrease in glycerol may respond to a photoperiod signal as opposed to initiation which is triggered by low temperature. The initial increase in glycerol level is supported by liver glycogen but high sustained glycerol level is dependent upon dietary carbohydrate and protein. The metabolic pathways leading to glycerol involve flux from glycogen/glucose to the level of dihydroxyacetone phosphate (DHAP) via the initial part of glycolysis and from amino acids via a truncated gluconeogenesis again to the level of DHAP. DHAP in turn is converted to glycerol 3-phosphate (G3P) and then directly to glycerol. The key to directing DHAP to G3P is a highly active glycerol 3-P dehydrogenase. G3P is converted directly to glycerol via G3P phosphatase, the rate-limiting step in the process. The transition to glycerol production is associated with increased activities of enzymes at key loci in the top part of glycogenolysis/glycolysis. Curtailment of the final section of glycolysis may reside at the level of pyruvate oxidation with an inactivation of pyruvate dehydrogenase (PDH) driven by increased levels of PDH kinase. Enzymes associated with amino acid trafficking are elevated as is the pivotal enzyme phosphoenolpyruvate carboxykinase.

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Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia

Cited by 24 publications

References 34 publications

Low temperature directly activates the initial glycerol antifreeze response in isolated rainbow smelt (Osmerus mordax) liver cells

Low temperature directly activates the initial glycerol antifreeze response in isolated rainbow smelt (Osmerus mordax) liver cells

Glycerol loss to water exceeds glycerol catabolism via glycerol kinase in freeze-resistant rainbow smelt (Osmerus mordax)

Rainbow smelt: the unusual case of cryoprotection by sustained glycerol production in an aquatic animal

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