Gluconeogenesis Flashcards
where does gluconeogenesis occur primarily?
in the liver
what is the first step of gluconeogenesis, starting with pyruvate?
pyruvate carboxylase uses 2 ATP to add CO2 to pyruvate, producing oxaloacetate
what enzyme is used in the second step to decarboxylate and phosphorylate oxaloacetate? what products form?
phosphoenolpyruvate carboxykinase (PEPCK) oxaloacetate turns into phosphoenolpyruvate and CO2.
phosphoenol pyruvate undergoes several steps to become fructose_________
fructose-1,6-bisphosphate
(the intermediate steps inc. both 2,2 and 2,3 phosphoglycerate, and glyceraldehyde 3-phosphate and dihydroxyacetone phosphate)
what does F-1,6-bP get turned into?
Fructose-6-Phosphate (F6P)
What does F6P get turned into?
Glucose-6-Phosphate (G6P)
What does G6P get turned into?
glucose
what enzyme turns F-1,6-bP into F6P?
fructose-1,6-bisphosphatase
what enzyme turns G6P into glucose?
glucose-6-phosphatase
what are the 4 major enzymes in gluconeogenesis?
pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), f-1,6-bisphosphatase, g-6-phosphatase
which step uses 2 GTP molecules?
second step where phosphoenolpyruvate carboxykinase (PEPCK) turns oxaloacetate into phosphoenolpyruvate
How many ATP, GTP, and NADH are used during one round of gluconeogenesis?
4 ATP, 2 GTP, and 2 NADH
Fructose-1,6-bisphosphatase catalyzes the removal of a ______ group from F-1,6-bP to form F6P
phosphate
F6P is _____ to become G6P
isomerized
G6P is _____ to become glucose
dephosphorylated
Why must G6P be dephosphorylated in the liver before released from the liver?
because G6P is charged and cannot cross the cell membrane. Only glucose can cross the cell membrane and be delivered into the bloodstream
Since glycolysis is such a thermodynamically favorable process, how is the reverse process of gluconeogenesis made thermodynamically favorable?
there are 3 major steps in gluconeogenesis that have a deltaG > 0, which are made thermodynamically favorable by coupling the reactions to the hydrolysis of high energy phosphate bonds of GTP and ATP
Why can free fatty acids no be converted into glucose during starvation?
because acetyl-CoA cannot be used in gluconeogenesis (which helps explain why the glycerol backbone of a triglyceride can)
what is futile cycling?
refers to running 2 processes with opposite functions/roles at the same time
what is reciprocal control?
refers to the same molecule regulating 2 enzymes, each one from an opposing pathway, in opposite ways. i.e. AMP activate PFK (glycolysis) and inhibits F-1,6-bPase (gluconeogenesis).
How does fructose-2,6-bisphosphate (F-2,6-BP) exert reciprocal control on glycolysis and gluconeogenesis?
Presence of F26BP stimulates glycolysis while simultanesouly inhibiting gluconeogenesis. The absence of F26BP has the opposite affect.
F26BP is a large protein whose intracellular concentration is controlled by both insulin and glucagon. Insulin stimulates production of F26BP, which then stimulates PFK (glycolysis) and inhibits F16bPase (gluconeogenesis). Glucagon stimulates breakdown of F26BP, so the low amount of F26BP stimulates F16bPase and inhibits PFK.
In a pathway, those enzymes which catalyze irreversible (i.e. exergonic) rxns are frequently sites of _____
regulation
increased concentrations of intermediates in a pathway generally serve to _____ the activity of that pathway
decrease
i.e. increase citrate decreases the activity of of PFK in glycolysis
Each pathway responds to the energy state of the cell. Cellular respirations is stimulated by energy ___1____ and inhibited by energy __2___
- deficits (i.e. high ADP to ATP ratio or high NAD+ to NADH ratio)
- surpulses (i.e. high ATP to ADP ratio or high NADH to NAD+ ratio)
What is the major regulatory step in gluconeogenesis? Name 1 positive regulator and 2 negative regulators of it.
F16bPase
positive regulator = ATP
negative regulators = F26BP and AMP
Gluconeogenesis generates new glucose molecules from precursors such as pyruvate, _____, ___ ___, and ____.
oxaloacetate, amino acids, and glycerol
What prevents futile cycles in a cell?
reciprocal regulation
When glycogen is depleted, gluconeogenesis can generate glucose from precursors pyruvate, _____, and ___ ____ intermediates
lactate, and Kreb cycle intermediates
