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Jan 27- Gluconeogenesis

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Biomedical Sciences
BMSC 230
Jon Stone

January 27 , 2011 Galactosemia: increased concentration of galactose in blood - Due to conversion of galactose to galactitol - Cannot utilize lactose Lactose Intolerance: lactose cannot be broken down into glucose and galactose - Lactase deficiency - Causes abnormal pain, cramps, etc Pentose Phosphate Pathway G6P + 2NAD + H2O Ru5P + 2NADPH + 2H + CO 2 (oxidative part) 3Ru5P 2F6P + Gly-3-P Therefore 3 molecules of G6P yield… 3G6P + 6NAD + 3H20 2F6P + Gly-3-P + 6NADPH + 6H + 3CO 2 Gluconeogenesis Glycogenolysis: breakdown of glycogen Glycolysis: breakdown of glucose Glycogenesis: synthesis of glycogen Gluconeogenesis: synthesis of new glucose - Formation of glucose from non-hexose precursors - Exists in all animals, plants, fungi and micro-organisms - In animals, precursors are lactate, pyruvate, glycerol and most of the amino acids - In plants, stored fats and proteins are converted into the disaccharide sucrose - In micro-organisms, simple organic compounds like acetate, lactate and proprionate are converted to glucose - An energy requiring process - Mainly occurs in the liver and sometimes in the kidneys 1 BYPASS If precursor is pyruvate (left side of diagram) - Pyruvate is transported into the mitochondria - Pyruvate is carboxylated into oxaloacetate Pyruvate Oxaloacetate - Irreversible reaction - Acetyl-CoA activates enzyme - Addition of carboxylate group - Get energy from hydrolysis of ATP from ADP + Pi - Biotin is a coenzyme - Oxaloacetate cannot be transported outside the mitochondria - Oxaloacetate is reduced to malate Oxaloacetate Malate - NADH is oxidized to NAD+ - Oxaloacetate is reduced to malate - Reversible reaction - Malate is transported across the mitochondrial membrane into cytosol - Malate is converted back to oxaloacetate (reversal of above reaction) o Malate is oxidized to oxaloacetate o NAD+ is reduced to NADH (this production of NADH allows gluconeogenesis to operate) - Oxaloacetate is converted to PEP (phosphoenolpyruvate) Oxaloacetate PEP - Decarboxylation (release of CO2) - Phosphorylation (add P group) - Comes from hydrolysis of GTP to GDP - Reversible reaction - Need 2 ATP and 2 GTP to convert 2 pyruvate to 2 PEP - PEP carboxykinase is the only enzyme is the living system that has no activators or inhibitors o Regulates by changing the amount of the enzyme o Can increase or decrease amount within 30 mins If precursor is lactate (right side of diagram) - Lactate is oxidized to pyruvate - NAD+
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