Lecture 13 - Gluconeogenesis Flashcards
Is gluconeogenesis the exact reverse of glycolysis?
NO - differs at 3 steps
Gluconeogenesis converts ___ back to ___
converts pyruvate back to glucose
When will gluconeogenesis occur?
in times of fasting
Gluconeogenesis is a pathway for forming glucose using ______ precursors
non-carbohydrate precursors
Name some non-carbohydrate precursors that can be used in gluconeogenesis
lactate, glycerol, and numerous amino acids
Gluconeogenesis occurs almost exclusively in…
the liver
Why is gluconeogenesis so important?
It’s important in maintaining blood glucose levels
What is the rate-limiting step in gluconeogenesis?
pyruvate—>—>PEP
The conversion of pyruvate to phosphoenolpyruvate requires ___ steps. Name them
2 steps:
pyruvate—>oxaloacetate
oxaloacetate–>phosphoenolpyruvate
pyruvate—> oxaloacetate
is catalyzed by the enzyme….
Pyruvate Carboxylase
oxaloacetate->PEP
is catalyzed by the enzyme….
Phosphoenolpyruvate Carboxykinase
Where is the enzyme pyruvate carboxylase located?
in the matrix of the mitochondria
Since the enzyme pyruvate carboxylase is located in the mitochondria, what must happen to pyruvate?
cytosolic pyruvate must be transported into the mitochondria through the pyruvate transport system
What is the rate limiting ENZYME in gluconeogenesis?
phosphoenolpyruvate
carboxykinase
the production of oxaloacetate is catalyzed in the _____
mitochondria
the conversion of oxaloacetate –> PEP occurs in…
the cytosol
Since the conversion of oxaloacetate–>PEP occurs in the mitochondria…
oxaloacetate must be indirectly transported to the inner mitochondrial membrane
What are the 2 conversions by which oxaloacetate enters the inner mitochondrial membrane?
- Reduction to malate
- Transamination to aspartate
The 2 conversions involved in transporting oxaloacetate into the inner mitochondrial membrane are…
near equilibrium
What enzyme catalyzes the reduction to malate?
malate dehydrogenase
What enzyme catalyzes the transamination to aspartate?
aspartate aminotransferase
What is the gluconeogenesis reaction that bypasses the PFK step in glycolysis?
Fructose-1,6-biphosphate
–>
Fructose-6-Phosphate
What enzyme catalyzes the conversion of Fructose-1,6-biphosphate to fructose-6-phosphate?
fructose-1,6-biphosphatase
What is the mechanism of the reaction catalyzed by fructose-1,6-biphosphatase?
the hydrolysis of the phosphate bond
Fructose-1,6-biphosphatase is activated by what molecule?
citrate
Fructose-1,6-biphosphatase is allosterically INHIBITED by what molecule?
fructose-2,6-biphosphate
What is the last step of gluconeogenesis and what enzyme catalyzes it?
Glucose-6-phosphate->
Glucose
catalyzed by glucose-6-phosphatase
The regulation of Glucose-6-Phosphate -> Glucose is regulated through ____ means
genetic
glucose-6-phosphate–> glucose is INCREASED during…..
starvation
directed by glucagon
glucose-6-phosphate->
glucose is SUPPRESED in ___ state directed by ____
fed state directed by insulin
When does the pancreas release insulin?
when blood sugar (glucose)enters our blood stream
What does insulin do?
helps glucose enter the body’s cells so it can be used for energy
ALSO
signals the liver to store glucose as glycogen for later use
Insulin ___ blood glucose levels
lowers
During a meal, glucose moves from the ____ to the ___
from the digestive tract to the bloodstream
When we eat something, _____ release is triggered, activating _____ synthesis in the __ and ___
when we eat something, INSULIN release is triggered, activating GLYCOGEN synthesis in the LIVER and MUSCLE
After a meal, what happens to glucose concentration?
it drops
When our glucose concentration decreases after a meal, _____ release is decreased and ___ release is stimulated
INSULIN release is decreased and GLUCAGON release is stimulated
Epinephrine is released in response to ____ blood glucose
low
epinephrine stimulates….
glycogen breakdown in the liver
What are the target(s) of insulin?
liver, muscle, others
What is the origin of insulin?
pancreatic-beta cell
What are the target (s) of glucagon?
ONLY the liver
What is the origin and target of epinephrine?
origin = adrenal gland
target= liver, muscle, others
What is a major consumer of glucose in the resting state?
skeletal muscle
During exercise, is glucose utilization increased or decreased?
increased 100 fold
What is another term for the state the body is in after eating a meal (when blood glucose conc drops)
the postprandial state
the regulation of muscle metabolism is largely ____
intrinsic
During exercise, blood flow is shunted away from the ___ and toward ____
away from the liver and towards muscle
In the post-exercise state, blood flow returns to the ____ and excess ___ accumulated by muscle glycolysis is converted to glucose by liver ______
blood flow returns to the LIVER and excess LACTATE accumulated by muscle glycolysis is converted to glucose by liver GLUCONEOGENESIS
Exercise causes a rise in intracellular…
calcium ions
_____ also increases cytosolic calcium ions
epinephrine
Cytosolic [Ca]+ concentration stimulates….
liver glycogen breakdown
calcium activates ___ breakdown which is important during ____
glycogen breakdown, exercise
The pentose phosphate shunt occurs in….
nearly all cells
The pentose phosphate shunt has 2 distinct contributions to the cell:
- Partially oxidize glucose-6-phosphate and generate NADPH
- Produce sugar phosphates including ribose phosphates
In the pentose phosphate shunt, NADPH is utilized as a….
reducing agent
in the pentose phosphate shunt, there is a __ stage and a __ stage
oxidative stage and nonoxidative stage
All of the reactions of the oxidative stage of the pentose phosphate shunt are metabolically _____
irreversible
give the formula for the oxidative stage of the pentose phosphate shunt
Glucose-6-P + 2NADP+
–> Ribulose-5-Phosphate + CO2 + 2NADPH
Give the enzymes that catalyze the 1st, 2nd, and 3rd steps of the oxidative stage of the pentose phosphate
1st step - glucose-6-pDH
2nd step - lactonase
3rd step - 6-p-gluconateDH
In the nonoxidative stage of the pentose phosphate shunt, all reactions are….
near equilibrium
In the nonoxidative stage, _______ undergoes 2 reactions:
ribulose-5-phosphate
- Epimerase reaction (special type of isomerase)
- Isomerase reaction
The intermediates of the nonoxidative stage can be incorporated into….
ribonucleotides
What are the 2 intermediates in the nonoxidative stage?
glyceraldehyde-P
Fructose-6-p
BOTH CAN ENTER GLYCOLYSIS WHICH GENERATES NO WASTE
The conversion to produce the 2 intermediates is performed by 2 enzymes:
transketolase
transaldolase
in the transketolase enzyme, the cleavage occurs between the carbonyl and the ___ carbon
alpha carbon
in the transaldolase enzyme, the cleavage occurs between the carbonyl and the ___ carbon
beta
How is NADPH production and r5P distributed?
based on cellular demand.