Gluconeogenesis

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gluconeogenesis

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the synthesis of glucose from small molecule precursors such as pyruvate
We will see that the anabolic pathway (gluconeogenesis) is not simply the reverse of the catabolic pathway (glycolysis), though some reactions are shared

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Major sites for Glucose Consumption

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Brain and muscle are the major sites of glucose consumption. But liver and kidney account for almost all gluconeogenesis. Glucose is then transported to where it is needed via bloodstream

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gluconeogenesis

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7 of the reactions of glycolysis are shared. The 3 steps that are highly exergonic are replaced by four different reactions and the enzymes in gluconeogenesis

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Pyruvate carboxylase

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converts pyruvate to oxaloacetate

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PEP carboxykinase

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makes PEP from oxaloacetate

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fructose-1,6- bisphosphatase

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Conversion of fructose-1,6- bisphosphate to fructose-6- phosphate requires a specific phosphatase,

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Glucose-6-phosphatase

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dephosphorylates glucose-6- phosphate

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Pyruvate carboxylase

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contains biotin covalently linked to a lysine residue
Biotin functions as a carboxyl group carrier

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Decarboxylation of oxaloacetate

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of oxaloacetate provides the driving force, two high energy NTPs
are consumed

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Gluconeogenesis consumes

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4 ATP and 2 GTP and 2 NADH for each glucose
molecule synthesized

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Phosphate ester Hydrolysis

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Thermodynamically favorable. activated by citrate (which inhibits PFK) and is inhibited by fructose-2,6-bisphosphate and AMP (which activate PFK). So there is reciprocal regulation of glycolysis and Gluconeogensis

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PFK-2

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F-6-P allosterically activates PFK-2

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Regulations of Gluconeogenesis

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F-6-P to F-1,6-P inhibited by F2, 6BP & AMP. PEP to Pyr is activated by Acetyl-CoA