BIOC 2300 Lecture Notes - Lecture 18: Pyruvate Carboxylase, Phosphoenolpyruvate Carboxykinase, Oxaloacetic Acid

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Carbohydrate Metabolism: Glycolysis and Gluconeogenesis
February 26-29, 2016
……
Graphical representations of the free energy changes of glycolysis:
Steps 1,3 and 10 are irreversible reactions
o Good candidates for regulation
o Different reverse reactions are catalyzed by different enzymes for the synthesis of
glucose
Gluconeogenesis
Humans use 160g of glucose per day
In the absence of dietary carbs, glucose must be made from non-carbohydrate precursors
GLUCONEOGENSIS
Brain need 75% of glucose
No fatty acids in substrate!
Net reaction: 2 pyruvate + 2 NADH + 6 ATP glucose + 2 NAD+ + 6 ADP
Therefore, gluconeogenesis is exact reversal of glycolysis
Gluconeogenesis:
Not a straight forward reversal of glycolysis
o Highly exergonic steps must be circumvented
o Reversible reactions are the same between processes
Glucolytic enzymes not used in gluconeogenesis:
If glycolysis and glyconeogensis occurred simultaneously, there would be a net consumption of
ATP.
NET: 4 ATP 4 ADP + 4 Pi
Futile cycle
Therefore, reciprocal reactions
Reminder: glucose phosphorylation by hexokinase has a large negative G
Hexokinase reaction - G = -16.7
Exact reversal: G = + 16.7
Therefore, a different enzyme catalyzes gluconeogenesis
o Glucose phosphatase
See net hydrolysis diagram*
Reversal of the alst step of glycolysis: for gluconeogenesis, the pyruvate is first converted to
oxaloacetate then to phosphoenolpyruvate
Pyruvate carboxylase and phosphoelnolpyruvate carboxyl kinase (PEPCK) are two of the
most important gluconeogenic enzymes and regulatory proteins
Pyruvate carboxylase requires ATP to carboxylate pyruvate to oxaloacetate
PEPCK requires GTP to decarboxylates and phosphorylates oxaloacetate to PEP
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Document Summary

Graphical representations of the free energy changes of glycolysis: steps 1,3 and 10 are irreversible reactions, good candidates for regulation, different reverse reactions are catalyzed by different enzymes for the synthesis of glucose. Gluconeogenesis: humans use 160g of glucose per day. In the absence of dietary carbs, glucose must be made from non-carbohydrate precursors. Gluconeogensis: brain need 75% of glucose, no fatty acids in substrate, net reaction: 2 pyruvate + 2 nadh + 6 atp glucose + 2 nad+ + 6 adp, therefore, gluconeogenesis is exact reversal of glycolysis. Gluconeogenesis: not a straight forward reversal of glycolysis, highly exergonic steps must be circumvented, reversible reactions are the same between processes, glucolytic enzymes not used in gluconeogenesis: If glycolysis and glyconeogensis occurred simultaneously, there would be a net consumption of. Atp: net: 4 atp 4 adp + 4 pi, futile cycle, therefore, reciprocal reactions.

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