12 Carbohdrates - GNG and Alcohol

12 Carbohdrates - GNG and Alcohol - Carbohydrates:...

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Carbohydrates: Gluconeogenesis Alcohol Metabolism HNFE 3025 Fall 2009
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Maintaining Blood Glucose Between meals, liver releases ~150 mg of glucose per min to maintain euglycemia at rest. If there are 70 g of stored glycogen in liver, there is enough to maintain blood glucose for ~ 7.75 h of rest. If the person exercises, output of glucose from liver can exceed 1.2 g per min Considering the importance of blood glucose, there must be another way to make it in liver to replace dwindling supplies of liver glycogen 2
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Obligatory Glucose Users CNS needs about 125 g of glucose per day Other obligatory glucose users need an additional 30-40 g/d Storing fat as TG uses glucose Therefore just to rest and do no exercise, glucose needs ~160 g/d If we exercise, glucose needs go up even further. 3
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Gluconeogenesis (GNG) As the name implies, it is the synthesis of new glucose from non-carbohydrate precursors glycerol, lactate, pyruvate, propionate and carbon skeletons of amino acids Of the 20 common amino acids we need to make proteins, 18 have all or part of their carbon skeletons that can be converted to glucose This process takes place primarily in liver (90%), and to a small extent in kidney (10%). 4
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Glycolysis vs. GNG Opposing processes using many of the same enzymes Like a single track section of a railroad, cannot have two trains going in opposite direction Glycolysis is favored and GNG is inhibited or Glycolysis inhibited and GNG favored 5
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Overall GNG Pathway 6 Starting from pyruvate, 4 new reactions are needed – catalyzed by: Pyruvate carboxylase Phosphoenolpyruvate carboxykinase (PEPCK) Fructose 1,6- bisphosphatase Glucose 6- phosphatase 3 reactions of glycolysis are not reversible Glucokinase PFK1 Pyruvate kinase Partial reversal of glycolytic pathway is used, at least the equilibrium reactions. Potential futile cycles if  both enzymes are  active at same time Pyruvate kinase can  be inactivated by  phosphorylation blnk
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Pyruvate Carboxylase Catalyzes the ATP-dependent carboxylation of pyruvate (3C) to make oxaloacetate (4C) A biotin-containing enzyme – irreversible reaction • Bicarbonate is the substrate, not CO 2 This reaction takes place in mitochondrial matrix, so cytosolic pyruvate must be transported across inner membrane to matrix Acetyl CoA is an obligatory activator – What does this mean? (without it, GNG cannot go) 7
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Catalyzes an equilibrium reaction that uses oxaloacetate to produce PEP. Can take place in the mitochondrial matrix (~50%) or the cytosol (~50%) Phosphoenolpyruvate Carboxykinase (PEPCK) 8
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Once PEP is generated in the cytosol, the reactions of glycolysis can be reversed back to Fructose 1,6-bisphosphate F 1,6-P 2 to F 6-P cannot occur because the PFK1 reaction is irreversible (non-equilibrium). But, another enzyme FRUCTOSE 1,6-BIS-PHOSPHATASE
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This note was uploaded on 03/23/2010 for the course HNFE 3025 taught by Professor Mwhulver during the Spring '10 term at Virginia Tech.

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12 Carbohdrates - GNG and Alcohol - Carbohydrates:...

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