Bio 30 Gluconeogenesis Flashcards
What is the main purpose of gluconeogenesis?
To maintain the blood glucose levels during fasting. It provides the energy that the RBC’s and the brain need to function since they cannot use fat like other cells to produce energy.
Describe very general lipolysis reaction.
Lipolysis is the breakdown of TAG’s into glycerol and fatty acids.
In very general terms, what is beta-oxidation?
Breakdown of fatty acids into acetyl-coa, NADH, FADH2
In general terms, what is ketogenesis?
Conversion of acetyl-coa into ketones for export.
Where does gluconeogenesis occur?
Only in the liver and kidney cortex.
Does gluconeogenesis produce or use energy?
It uses energy to build an energy rich molecule that can then be used to be exported. It requires 4 ATP, 2 GTP, 2 NADH for each glucose.
What are the precursors for gluconeogenesis?
Amino Acids (to make pyruvate)
Lactate (to make pyruvate)
Glycerol (why?)
Propionyl-CoA (from odd chain AA’s to make succinyl-CoA)
What are the regulatory enzymes for gluconeogenesis?
Pyruvate Carboxylase (pyruvate–>OAA)
PEP Carboxykinase (OAA–>PEP)
FBPase-1 (Rate limiting, F1,6bisP–>F6P)
G6Pase (G6P–>Glucose)
How is blood glucose homeostasis maintained over the five phases of time post a mixed meal?
Phase I (0-4hrs): dietary carbs Phase II (5-16hrs): glycogen mostly, little gluconeogenesis Phase III (16-24hrs): liver gluconeogenesis mostly, little glycogen Phase IV (>24hrs): 50/50 liver and kidney gluconeogenesis Phase V (>2days): Same
What are the major fuel sources for the cells of the body in the five phases after a meal?
Phase I (0-4hrs): dietary carb oxidation Phase II (5-16hrs): fatty acid oxidation Phase III (16-24hrs): fatty acids, start to see little ketone use Phase IV (>24hrs): fatty acid oxidation and more significant ketone use Phase V (>2days): Same
Describe the first regulatory step of gluconeogenesis involving pyruvate carboxylase.
Pyruvate + ATP + CO2–>OAA + ADP
Requires Biotin to attach the CO2
Activated by Acetyl-CoA
Has two functions: Prime TCA cycle, and provide OAA for gluconeogenesis
In the fasting state, will pyruvate in the liver be used more for TCA priming or gluconeogenesis?
Because of beta oxidation, NADH and ATP will build up and inhibit ICDH which will slow the TCA cycle significantly. This causes most of the OAA from the pyruvate to be used for gluconeogenesis.
How does OAA get from the mitochondria to the cytosol?
Through the malate-aspartate shuttle.
Describe the reaction that converts OAA to PEP.
In cytosol
Uses PEP carboxykinase to decarboxylate and phosphorylate OAA to become PEP
Requires GTP
Describe the rate limiting step of gluconeogenesis.
FBPase-1 converts F1,6bisP into F6P
FBPase-1 inhibited by F2,6bisP
How does the I/G ratio affect the rate limiting steps of glycolysis and gluconeogenesis.
For both reactions, the rate limiting step is between F6P and F1,6bisP.
The enzymes used are PFK-1 and FBPase-1.
Both are allosterically affected by F2,6bisP.
Levels of F2,6bisP are controlled by the I/G ratio. When high, PKF-2 is active and dephosphorylated and this activates PKF-1 and inhibits FBPase-1. When I/G is low, PFK-2 is phosphorylated and inactivated. PFK-1 is then inhibited and FBPase-1 is activated.
Describe the last regulatory step of gluconeogenesis.
G6P is converted to glucose for export from the liver and kidneys by G6Pase.
What gluconeogetic precursors also regulate gluconeogenesis?
Availability of amino acids, glycerol, and lactate all influence the rate of glucose synthesis in the liver.
What is the Cori cycle?
It links the activity of the liver with activity in the muscles or RBC’s. The liver produces glucose through gluconeogenesis and the muscles or RBC’s use the glucose anaerobically to produce lactate which is shipped back to the liver as a precursor for gluconeogenesis.
Explain protein sparing effect and the processes and molecules involved.
It all starts with beta-oxidation.
Beta-Ox produces A-CoA, NADH, FADH2
A-CoA is used for ketogenesis
NADH, FADH2 make ATP and slow the TCA cycle
Slow TCA means that OAA is used for Gluconeogenesis and not put through the TCA for the energy of the cell.
What are the protein sparing molecules in the fed, and fasting states?
Fed: dietary carbs
Short fast: glycogen
Long fast: ketones
