gluconeoglycogen - - GLUCONEOGENESIS - Definition: the...

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-- GLUCONEOGENESIS -- Definition : the biosynthesis of glucose primarily from pyruvate and its precursors. The liver is the major location for gluconeogenesis.
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Why do we produce glucose? Need to maintain glucose levels within a narrow range in blood. Brain, erythrocytes, and muscles in exertion use glucose at a rapid rate and require glucose between meals, especially after several hours.
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What is the major precursor? The major precursor for glucose biosynthesis is pyruvate.
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What are the sources of pyruvate? lactate mostly from muscle. Lactate is produced in great quantities during exertion. Lactate is released from the muscles to the blood and travels to the liver for conversion to pyruvate and, ultimately to glucose.
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some amino acid carbon skeletons- from diet or breakdown of muscle protein during starvation- most important is alanine TCA cycle intermediates Note: that glucose cannot be made from acetyl CoA
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Gluconeogenesis - beginning GDP + CO 2 phosphoenolpyruvate GTP phosphoenolpyruvate carboxykinase BYPASS 1 oxaloacetate Other amino acids ADP + P i pyruvate carboxylase ATP + CO 2 ( pyruvate kinase) PYRUVATE (3C) lactate, alanine, some amino acids
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fructose 1,6- bis phosphate aldolase triose phosphate isomerase dihydroxyacetone glyceraldehyde phosphate 3-phosphate glyceraldehyde NAD + +P i 3-phosphate NADH +H + dehydrogenase 1,3- bis phosphoglycerate ADP phosphoglycerate kinase ATP 3-phosphoglycerate phosphoglyceromutase 2-phosphoglycerate enolase phospho enol pyruvate
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GLUCOSE glucose P i BYPASS 3 6-phosphatase ( hexokinase) Glucose 6-phosphate phosphogluco- isomerase Fructose 6-phosphate BYPASS 2 fructose P i ( phospho- 1,6 bisphosphatase fructokinase) Fructose 1,6- bis phosphate
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Bypass number 1. Pyruvate to phosphoenolpyruvate . This bypasses pyruvate kinase. Complex scheme .
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a) pyruvate to oxaloacetate Enzyme = pyruvate carboxylase Pyruvate has transport system to enter mitochondria Enzyme located inside mitochondria . Only this enzyme of gluconeogenesis pathway is mitochondrial.
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Reaction : pyruvate + CO 2 + ATP + H 2 O oxaloacetate + ADP + P i Pyruvate carboxylase requires biotin as cofactor- Carboxylations involving CO 2 almost always use the vitamin biotin pyruvate carboxylase- acetyl- CoA absolutely required activator
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For gluconeogenesis, oxaloacetate must leave the mitochondria because all the rest of the gluconeogenesis enzymes are in the cytosol. mitochondrial membranes are nearly impermeable to oxaloacetate. So how does it get out?
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b) transport - three steps malate dehydrogenase mitochondrial enzyme Oxaloacetate + NADH + H + malate (mitochondria) + NAD + malate can be malate oxaloacetate transported through HO O the mitochondrial C-COO - membrane HCH COO -
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malate dehydrogenase -- cytosolic enzyme malate + NAD + oxaloacetate + (cytosolic) NADH + H +
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c) The GTP-dependent decarboxylation of oxaloacetate Enzyme = PEP carboxykinase c ytosolic enzyme,
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This note was uploaded on 09/18/2011 for the course BCH 4024 taught by Professor Allison during the Spring '08 term at University of Florida.