Limits...
Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings.

Jalloh I, Carpenter KL, Helmy A, Carpenter TA, Menon DK, Hutchinson PJ - Metab Brain Dis (2014)

Bottom Line: A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked.Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed.We summarise the data published from these techniques and review their potential uses in the clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167 Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK, ij232@cam.ac.uk.

ABSTRACT
The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study cerebral glucose metabolism with a focus on those used in clinical TBI studies. Arterio-venous measurements provide a global measure of glucose uptake into the brain. Microdialysis allows the in vivo sampling of brain extracellular fluid and is well suited to the longitudinal assessment of metabolism after TBI in the clinical setting. A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked. Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed. We summarise the data published from these techniques and review their potential uses in the clinical setting.

No MeSH data available.


Related in: MedlinePlus

Glycolysis and the tricarboxylic acid cycle: Glucose is the preferred substrate for the brain, although the brain can take up lactate, other monocarboxylic acids and ketone bodies under certain circumstances, for example, during the perinatal period. Once it enters cells, glucose is metabolised through glycolysis to pyruvate. Glycolysis (also termed Embden-Meyerhof pathway) is the series of reactions that results in the breakdown of glucose, generating pyruvate, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). It is a truly fundamental pathway, found throughout nature and proceeds without the need for oxygen. The ten key enzymatic steps, in which 2 ATP molecules are consumed early on but then paid back later with the generation of 4 ATP molecules per glucose molecule, so the net production of ATP is 2 molecules per molecule of glucose, takes place in the cytoplasm. There are three key regulatory points catalysed by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase. These reactions are essentially irreversible whereas the other enzymatic steps exist in equilibrium. Pyruvate is converted to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle, within mitochondria. The TCA cycle results in the transfer of electrons (from NADH and succinate), to electron transport chains (ETC.) located in the inner mitochondrial membrane, which ultimately deposit on oxygen molecules. Thus the TCA cycle generates carbon dioxide (also generated by the pyruvate dehydrogenase step prior to TCA cycle) and the ETC generates water. The ETCs pump protons across the inner mitochondrial membrane, maintaining a gradient of protons across the membrane. Protons then flow down their concentration gradient, through ATP synthetases (ATPase), resulting in the generation of ATP, the cells’ widely used energy currency. Energy production from glucose is intrinsically related to neurotransmission. Glutamate spins off the TCA cycle from α-ketoglutarate (αKG), an intermediate of the TCA cycle. Glutamate can be converted reversibly into glutamine. Glutamate can also be converted into gamma-aminobutyric acid (GABA). There is a constant cycle of glutamate released during neurotransmission, retrieved from synaptic junctions by astrocytes and returned to neurons as glutamine
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4555200&req=5

Fig2: Glycolysis and the tricarboxylic acid cycle: Glucose is the preferred substrate for the brain, although the brain can take up lactate, other monocarboxylic acids and ketone bodies under certain circumstances, for example, during the perinatal period. Once it enters cells, glucose is metabolised through glycolysis to pyruvate. Glycolysis (also termed Embden-Meyerhof pathway) is the series of reactions that results in the breakdown of glucose, generating pyruvate, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). It is a truly fundamental pathway, found throughout nature and proceeds without the need for oxygen. The ten key enzymatic steps, in which 2 ATP molecules are consumed early on but then paid back later with the generation of 4 ATP molecules per glucose molecule, so the net production of ATP is 2 molecules per molecule of glucose, takes place in the cytoplasm. There are three key regulatory points catalysed by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase. These reactions are essentially irreversible whereas the other enzymatic steps exist in equilibrium. Pyruvate is converted to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle, within mitochondria. The TCA cycle results in the transfer of electrons (from NADH and succinate), to electron transport chains (ETC.) located in the inner mitochondrial membrane, which ultimately deposit on oxygen molecules. Thus the TCA cycle generates carbon dioxide (also generated by the pyruvate dehydrogenase step prior to TCA cycle) and the ETC generates water. The ETCs pump protons across the inner mitochondrial membrane, maintaining a gradient of protons across the membrane. Protons then flow down their concentration gradient, through ATP synthetases (ATPase), resulting in the generation of ATP, the cells’ widely used energy currency. Energy production from glucose is intrinsically related to neurotransmission. Glutamate spins off the TCA cycle from α-ketoglutarate (αKG), an intermediate of the TCA cycle. Glutamate can be converted reversibly into glutamine. Glutamate can also be converted into gamma-aminobutyric acid (GABA). There is a constant cycle of glutamate released during neurotransmission, retrieved from synaptic junctions by astrocytes and returned to neurons as glutamine

Mentions: The aim of this review is to summarise what we know about the metabolic perturbations that characterise TBI with a focus on clinical studies. Specifically, we will focus on changes to glucose metabolism after moderate to severe TBI. See Fig. 2 for an overview of glucose metabolism. The most noticeable feature is that the injured brain can exhibit a relative rise in non-oxygen-consuming glucose metabolism. With the increasing clinical availability of techniques that provide insight into glucose metabolism, such as microdialysis and MRS it is important to review the available evidence with a view to improving our ability to interpret this data.Fig. 2


Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings.

Jalloh I, Carpenter KL, Helmy A, Carpenter TA, Menon DK, Hutchinson PJ - Metab Brain Dis (2014)

Glycolysis and the tricarboxylic acid cycle: Glucose is the preferred substrate for the brain, although the brain can take up lactate, other monocarboxylic acids and ketone bodies under certain circumstances, for example, during the perinatal period. Once it enters cells, glucose is metabolised through glycolysis to pyruvate. Glycolysis (also termed Embden-Meyerhof pathway) is the series of reactions that results in the breakdown of glucose, generating pyruvate, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). It is a truly fundamental pathway, found throughout nature and proceeds without the need for oxygen. The ten key enzymatic steps, in which 2 ATP molecules are consumed early on but then paid back later with the generation of 4 ATP molecules per glucose molecule, so the net production of ATP is 2 molecules per molecule of glucose, takes place in the cytoplasm. There are three key regulatory points catalysed by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase. These reactions are essentially irreversible whereas the other enzymatic steps exist in equilibrium. Pyruvate is converted to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle, within mitochondria. The TCA cycle results in the transfer of electrons (from NADH and succinate), to electron transport chains (ETC.) located in the inner mitochondrial membrane, which ultimately deposit on oxygen molecules. Thus the TCA cycle generates carbon dioxide (also generated by the pyruvate dehydrogenase step prior to TCA cycle) and the ETC generates water. The ETCs pump protons across the inner mitochondrial membrane, maintaining a gradient of protons across the membrane. Protons then flow down their concentration gradient, through ATP synthetases (ATPase), resulting in the generation of ATP, the cells’ widely used energy currency. Energy production from glucose is intrinsically related to neurotransmission. Glutamate spins off the TCA cycle from α-ketoglutarate (αKG), an intermediate of the TCA cycle. Glutamate can be converted reversibly into glutamine. Glutamate can also be converted into gamma-aminobutyric acid (GABA). There is a constant cycle of glutamate released during neurotransmission, retrieved from synaptic junctions by astrocytes and returned to neurons as glutamine
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4555200&req=5

Fig2: Glycolysis and the tricarboxylic acid cycle: Glucose is the preferred substrate for the brain, although the brain can take up lactate, other monocarboxylic acids and ketone bodies under certain circumstances, for example, during the perinatal period. Once it enters cells, glucose is metabolised through glycolysis to pyruvate. Glycolysis (also termed Embden-Meyerhof pathway) is the series of reactions that results in the breakdown of glucose, generating pyruvate, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). It is a truly fundamental pathway, found throughout nature and proceeds without the need for oxygen. The ten key enzymatic steps, in which 2 ATP molecules are consumed early on but then paid back later with the generation of 4 ATP molecules per glucose molecule, so the net production of ATP is 2 molecules per molecule of glucose, takes place in the cytoplasm. There are three key regulatory points catalysed by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase. These reactions are essentially irreversible whereas the other enzymatic steps exist in equilibrium. Pyruvate is converted to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle, within mitochondria. The TCA cycle results in the transfer of electrons (from NADH and succinate), to electron transport chains (ETC.) located in the inner mitochondrial membrane, which ultimately deposit on oxygen molecules. Thus the TCA cycle generates carbon dioxide (also generated by the pyruvate dehydrogenase step prior to TCA cycle) and the ETC generates water. The ETCs pump protons across the inner mitochondrial membrane, maintaining a gradient of protons across the membrane. Protons then flow down their concentration gradient, through ATP synthetases (ATPase), resulting in the generation of ATP, the cells’ widely used energy currency. Energy production from glucose is intrinsically related to neurotransmission. Glutamate spins off the TCA cycle from α-ketoglutarate (αKG), an intermediate of the TCA cycle. Glutamate can be converted reversibly into glutamine. Glutamate can also be converted into gamma-aminobutyric acid (GABA). There is a constant cycle of glutamate released during neurotransmission, retrieved from synaptic junctions by astrocytes and returned to neurons as glutamine
Mentions: The aim of this review is to summarise what we know about the metabolic perturbations that characterise TBI with a focus on clinical studies. Specifically, we will focus on changes to glucose metabolism after moderate to severe TBI. See Fig. 2 for an overview of glucose metabolism. The most noticeable feature is that the injured brain can exhibit a relative rise in non-oxygen-consuming glucose metabolism. With the increasing clinical availability of techniques that provide insight into glucose metabolism, such as microdialysis and MRS it is important to review the available evidence with a view to improving our ability to interpret this data.Fig. 2

Bottom Line: A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked.Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed.We summarise the data published from these techniques and review their potential uses in the clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167 Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK, ij232@cam.ac.uk.

ABSTRACT
The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study cerebral glucose metabolism with a focus on those used in clinical TBI studies. Arterio-venous measurements provide a global measure of glucose uptake into the brain. Microdialysis allows the in vivo sampling of brain extracellular fluid and is well suited to the longitudinal assessment of metabolism after TBI in the clinical setting. A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked. Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed. We summarise the data published from these techniques and review their potential uses in the clinical setting.

No MeSH data available.


Related in: MedlinePlus